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Intracranial artery stenting shows promising 1-year results
LOS ANGELES –
One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
Assessing restenosis frequency
“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
Intracranial stenting falls out of favor
The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.
The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.
That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
The WOVEN study
The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.
In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.
[embed:render:related:node:158134]
According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.
Encouraging data, but is it compelling?
“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.
“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.
WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.
SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.
LOS ANGELES –
One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
Assessing restenosis frequency
“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
Intracranial stenting falls out of favor
The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.
The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.
That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
The WOVEN study
The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.
In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.
[embed:render:related:node:158134]
According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.
Encouraging data, but is it compelling?
“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.
“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.
WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.
SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.
LOS ANGELES –
One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
Assessing restenosis frequency
“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
Intracranial stenting falls out of favor
The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.
The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.
That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
The WOVEN study
The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.
In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.
[embed:render:related:node:158134]
According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.
Encouraging data, but is it compelling?
“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.
“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.
WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.
SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.
REPORTING FROM ISC 2020
ICH survival lags in the community setting
LOS ANGELES – Although recent findings from circumscribed patient populations enrolled in intervention studies have shown improved survival rates in patients with a recent intracerebral hemorrhagic stroke, data from a large, observational study in the Netherlands suggested a much darker real-world picture, with a 6-month mortality of 64% identified in a total cohort of nearly 15,000 people followed prospectively starting in 1990.
In striking contrast to the survival pattern over time of patients in the same Dutch study who had a first acute ischemic stroke, which showed a statistically significant and meaningful cut in mortality for ischemic stroke patients during the 25-year period examined, survival rates for patients during the first months following a first intracerebral hemorrhage (ICH) stayed flat during 1991-2015, Reem Waziry, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The promising treatment advances [applied to patients] in the recent ICH trials may not be reflected in community-based treatment,” suggested Dr. Waziry, a research and teaching fellow in clinical epidemiology at the Harvard School of Public Health in Boston.
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The data she reported came from the Rotterdam Study, which followed unselected, older people in the Rotterdam community with no stroke history, and during 25 years of monitoring identified 162 incident ICH strokes and 988 acute ischemic strokes. Concurrently with Dr. Waziry’s talk at the conference, the data she reported were published in Stroke. The data she reported also showed that, during the 25 years studied, mortality at 3 years following a first ICH stroke rose to 73% on average.
During her talk, Dr. Waziry also presented an unpublished comparison of the 64% 6-month mortality in the Rotterdam Study with the 3- to 6-month mortality reported in the control arms of four recent, randomized intervention trials, including the MISTIE III trial. Among the four randomized trials Dr. Waziry selected to make this post-hoc comparison, the study with the highest mortality among control patients was MISTIE III, which showed about 25% mortality after 6 months. In contrast, the 19% 6-month mortality among ischemic stroke patients in the Rotterdam Study was roughly similar to the mortality seem in the control arms of some recent studies of interventions for patients with acute ischemic stroke.
[embed:render:related:node:137989]
The Rotterdam Study receives no commercial funding. Dr. Waziry had no disclosures.
SOURCE: Waziry R et al. ISC 2020, Abstract LB14.
LOS ANGELES – Although recent findings from circumscribed patient populations enrolled in intervention studies have shown improved survival rates in patients with a recent intracerebral hemorrhagic stroke, data from a large, observational study in the Netherlands suggested a much darker real-world picture, with a 6-month mortality of 64% identified in a total cohort of nearly 15,000 people followed prospectively starting in 1990.
In striking contrast to the survival pattern over time of patients in the same Dutch study who had a first acute ischemic stroke, which showed a statistically significant and meaningful cut in mortality for ischemic stroke patients during the 25-year period examined, survival rates for patients during the first months following a first intracerebral hemorrhage (ICH) stayed flat during 1991-2015, Reem Waziry, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The promising treatment advances [applied to patients] in the recent ICH trials may not be reflected in community-based treatment,” suggested Dr. Waziry, a research and teaching fellow in clinical epidemiology at the Harvard School of Public Health in Boston.
[embed:render:related:node:219151]
The data she reported came from the Rotterdam Study, which followed unselected, older people in the Rotterdam community with no stroke history, and during 25 years of monitoring identified 162 incident ICH strokes and 988 acute ischemic strokes. Concurrently with Dr. Waziry’s talk at the conference, the data she reported were published in Stroke. The data she reported also showed that, during the 25 years studied, mortality at 3 years following a first ICH stroke rose to 73% on average.
During her talk, Dr. Waziry also presented an unpublished comparison of the 64% 6-month mortality in the Rotterdam Study with the 3- to 6-month mortality reported in the control arms of four recent, randomized intervention trials, including the MISTIE III trial. Among the four randomized trials Dr. Waziry selected to make this post-hoc comparison, the study with the highest mortality among control patients was MISTIE III, which showed about 25% mortality after 6 months. In contrast, the 19% 6-month mortality among ischemic stroke patients in the Rotterdam Study was roughly similar to the mortality seem in the control arms of some recent studies of interventions for patients with acute ischemic stroke.
[embed:render:related:node:137989]
The Rotterdam Study receives no commercial funding. Dr. Waziry had no disclosures.
SOURCE: Waziry R et al. ISC 2020, Abstract LB14.
LOS ANGELES – Although recent findings from circumscribed patient populations enrolled in intervention studies have shown improved survival rates in patients with a recent intracerebral hemorrhagic stroke, data from a large, observational study in the Netherlands suggested a much darker real-world picture, with a 6-month mortality of 64% identified in a total cohort of nearly 15,000 people followed prospectively starting in 1990.
In striking contrast to the survival pattern over time of patients in the same Dutch study who had a first acute ischemic stroke, which showed a statistically significant and meaningful cut in mortality for ischemic stroke patients during the 25-year period examined, survival rates for patients during the first months following a first intracerebral hemorrhage (ICH) stayed flat during 1991-2015, Reem Waziry, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The promising treatment advances [applied to patients] in the recent ICH trials may not be reflected in community-based treatment,” suggested Dr. Waziry, a research and teaching fellow in clinical epidemiology at the Harvard School of Public Health in Boston.
[embed:render:related:node:219151]
The data she reported came from the Rotterdam Study, which followed unselected, older people in the Rotterdam community with no stroke history, and during 25 years of monitoring identified 162 incident ICH strokes and 988 acute ischemic strokes. Concurrently with Dr. Waziry’s talk at the conference, the data she reported were published in Stroke. The data she reported also showed that, during the 25 years studied, mortality at 3 years following a first ICH stroke rose to 73% on average.
During her talk, Dr. Waziry also presented an unpublished comparison of the 64% 6-month mortality in the Rotterdam Study with the 3- to 6-month mortality reported in the control arms of four recent, randomized intervention trials, including the MISTIE III trial. Among the four randomized trials Dr. Waziry selected to make this post-hoc comparison, the study with the highest mortality among control patients was MISTIE III, which showed about 25% mortality after 6 months. In contrast, the 19% 6-month mortality among ischemic stroke patients in the Rotterdam Study was roughly similar to the mortality seem in the control arms of some recent studies of interventions for patients with acute ischemic stroke.
[embed:render:related:node:137989]
The Rotterdam Study receives no commercial funding. Dr. Waziry had no disclosures.
SOURCE: Waziry R et al. ISC 2020, Abstract LB14.
REPORTING FROM ISC 2020
Recent treatment advances brighten prospects for intracerebral hemorrhage patients
LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.
“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.
The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.
“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
MISTIE III showcases better ICH outcomes
Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.
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However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.
The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.
When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.
“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.
She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
A message for acute-care clinicians
She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.
“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.
In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.
“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.
“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.
An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
More evidence needed to prove MISTIE’s hypothesis
According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.
Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.
Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.
But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.
“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.
Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.
LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.
“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.
The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.
“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
MISTIE III showcases better ICH outcomes
Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.
[embed:render:related:node:194606]
However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.
The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.
When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.
“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.
She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
A message for acute-care clinicians
She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.
“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.
In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.
“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.
“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.
An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
More evidence needed to prove MISTIE’s hypothesis
According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.
Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.
Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.
But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.
“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.
Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.
LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.
“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.
The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.
“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
MISTIE III showcases better ICH outcomes
Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.
[embed:render:related:node:194606]
However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.
The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.
When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.
“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.
She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
A message for acute-care clinicians
She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.
“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.
In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.
“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.
“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.
An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
More evidence needed to prove MISTIE’s hypothesis
According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.
Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.
Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.
But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.
“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.
Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.
REPORTING FROM ISC 2020
Researchers develop score to predict risk of stroke among migraineurs with aura
LOS ANGELES – The study on which the risk score is based was presented at the International Stroke Conference sponsored by the American Heart Association. Migraine with aura, for which younger women are at higher risk, increases the risk of ischemic stroke. “With our new risk-prediction tool, we could start identifying those at higher risk, treat their risk factors, and lower their risk of stroke,” said Souvik Sen, MD, MPH, professor and chair of neurology at the University of South Carolina in Columbia, in a press release.
Risk groups significantly discriminated stroke risk
To create the score, Dr. Sen and colleagues examined data from the ARIC (Atherosclerosis Risk in Communities) cohort, which includes community-dwelling people in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis. Researchers have been following the participants since 1987. From this population, Dr. Sen and colleagues identified 429 participants with a history of migraine with aura. Most of these participants were women aged 50-59 years at their first visit. The researchers analyzed the association between potential risk factors and ischemic stroke using Cox proportional hazards analysis.
Of the 429 participants, 31 had an ischemic stroke during a follow-up period of 20 years. Dr. Sen’s group created a risk score by identifying five risk factors for stroke and assigning them points in proportion to their influence (i.e., their regression coefficients). They assigned diabetes mellitus – 7 points; age older than 65 years – 5 points; heart rate variability (i.e., the standard deviation of all normal-to-normal RR intervals) – 3 points; hypertension – 3 points – and sex – 1 point. Then the researchers calculated risk scores for each patient and defined a low-risk group (from 0-4 points), a moderate-risk group (5-10 points), and a high-risk group (11-21 points).
After 18 years of follow-up, the incidence of stroke was 3% in the low-risk group, 8% in the moderate-risk group, and 34% in the high-risk group. The hazard ratio for ischemic stroke in the high-risk group, compared with the low-risk group, was 7.35. Kaplan Meier curves indicated that the risk-stratification groups significantly discriminated stroke risk among the sample. The risk score should be validated in an independent population cohort, said the investigators.
Dr. Sen and colleagues did not report any funding for this study. Investigators reported receiving grants from the National Institutes of Health, the American Heart Association, and the American Academy of Neurology.
Score may leave important variables unexamined
One mechanism through which migraine increases the risk of stroke is the constriction of blood vessels, said Louis R. Caplan, MD, professor of neurology at Harvard Medical School in Boston and member of the editorial advisory board of Neurology Reviews. Triptans, which many patients use to treat migraine, also cause vasoconstriction. In addition, migraine increases blood coagulation.
Although the risk score developed by Dr. Sen and colleagues accounts for various comorbidities, it may not apply equally to all patients. “As I understand it, they’re just using migraine with aura as a single factor,” said Dr. Caplan. Variables such as prolonged aura, frequent episodes, and aura-related deficit are associated with increased risk of stroke, but the risk score does not examine these factors.
Patients with severe, long-lasting attacks or attacks that involve weakness or aphasia should receive prophylactic treatment to prevent vasoconstriction, such as verapamil (Verelan), said Dr. Caplan. Antithrombotic agents such as aspirin also may be appropriate prophylaxis. Whether effective treatment of migraine with aura decreases the risk of stroke remains unknown.
SOURCE: Trivedi T et al. ISC 2020. Abstract WMP117.
LOS ANGELES – The study on which the risk score is based was presented at the International Stroke Conference sponsored by the American Heart Association. Migraine with aura, for which younger women are at higher risk, increases the risk of ischemic stroke. “With our new risk-prediction tool, we could start identifying those at higher risk, treat their risk factors, and lower their risk of stroke,” said Souvik Sen, MD, MPH, professor and chair of neurology at the University of South Carolina in Columbia, in a press release.
Risk groups significantly discriminated stroke risk
To create the score, Dr. Sen and colleagues examined data from the ARIC (Atherosclerosis Risk in Communities) cohort, which includes community-dwelling people in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis. Researchers have been following the participants since 1987. From this population, Dr. Sen and colleagues identified 429 participants with a history of migraine with aura. Most of these participants were women aged 50-59 years at their first visit. The researchers analyzed the association between potential risk factors and ischemic stroke using Cox proportional hazards analysis.
Of the 429 participants, 31 had an ischemic stroke during a follow-up period of 20 years. Dr. Sen’s group created a risk score by identifying five risk factors for stroke and assigning them points in proportion to their influence (i.e., their regression coefficients). They assigned diabetes mellitus – 7 points; age older than 65 years – 5 points; heart rate variability (i.e., the standard deviation of all normal-to-normal RR intervals) – 3 points; hypertension – 3 points – and sex – 1 point. Then the researchers calculated risk scores for each patient and defined a low-risk group (from 0-4 points), a moderate-risk group (5-10 points), and a high-risk group (11-21 points).
After 18 years of follow-up, the incidence of stroke was 3% in the low-risk group, 8% in the moderate-risk group, and 34% in the high-risk group. The hazard ratio for ischemic stroke in the high-risk group, compared with the low-risk group, was 7.35. Kaplan Meier curves indicated that the risk-stratification groups significantly discriminated stroke risk among the sample. The risk score should be validated in an independent population cohort, said the investigators.
Dr. Sen and colleagues did not report any funding for this study. Investigators reported receiving grants from the National Institutes of Health, the American Heart Association, and the American Academy of Neurology.
Score may leave important variables unexamined
One mechanism through which migraine increases the risk of stroke is the constriction of blood vessels, said Louis R. Caplan, MD, professor of neurology at Harvard Medical School in Boston and member of the editorial advisory board of Neurology Reviews. Triptans, which many patients use to treat migraine, also cause vasoconstriction. In addition, migraine increases blood coagulation.
Although the risk score developed by Dr. Sen and colleagues accounts for various comorbidities, it may not apply equally to all patients. “As I understand it, they’re just using migraine with aura as a single factor,” said Dr. Caplan. Variables such as prolonged aura, frequent episodes, and aura-related deficit are associated with increased risk of stroke, but the risk score does not examine these factors.
Patients with severe, long-lasting attacks or attacks that involve weakness or aphasia should receive prophylactic treatment to prevent vasoconstriction, such as verapamil (Verelan), said Dr. Caplan. Antithrombotic agents such as aspirin also may be appropriate prophylaxis. Whether effective treatment of migraine with aura decreases the risk of stroke remains unknown.
SOURCE: Trivedi T et al. ISC 2020. Abstract WMP117.
LOS ANGELES – The study on which the risk score is based was presented at the International Stroke Conference sponsored by the American Heart Association. Migraine with aura, for which younger women are at higher risk, increases the risk of ischemic stroke. “With our new risk-prediction tool, we could start identifying those at higher risk, treat their risk factors, and lower their risk of stroke,” said Souvik Sen, MD, MPH, professor and chair of neurology at the University of South Carolina in Columbia, in a press release.
Risk groups significantly discriminated stroke risk
To create the score, Dr. Sen and colleagues examined data from the ARIC (Atherosclerosis Risk in Communities) cohort, which includes community-dwelling people in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis. Researchers have been following the participants since 1987. From this population, Dr. Sen and colleagues identified 429 participants with a history of migraine with aura. Most of these participants were women aged 50-59 years at their first visit. The researchers analyzed the association between potential risk factors and ischemic stroke using Cox proportional hazards analysis.
Of the 429 participants, 31 had an ischemic stroke during a follow-up period of 20 years. Dr. Sen’s group created a risk score by identifying five risk factors for stroke and assigning them points in proportion to their influence (i.e., their regression coefficients). They assigned diabetes mellitus – 7 points; age older than 65 years – 5 points; heart rate variability (i.e., the standard deviation of all normal-to-normal RR intervals) – 3 points; hypertension – 3 points – and sex – 1 point. Then the researchers calculated risk scores for each patient and defined a low-risk group (from 0-4 points), a moderate-risk group (5-10 points), and a high-risk group (11-21 points).
After 18 years of follow-up, the incidence of stroke was 3% in the low-risk group, 8% in the moderate-risk group, and 34% in the high-risk group. The hazard ratio for ischemic stroke in the high-risk group, compared with the low-risk group, was 7.35. Kaplan Meier curves indicated that the risk-stratification groups significantly discriminated stroke risk among the sample. The risk score should be validated in an independent population cohort, said the investigators.
Dr. Sen and colleagues did not report any funding for this study. Investigators reported receiving grants from the National Institutes of Health, the American Heart Association, and the American Academy of Neurology.
Score may leave important variables unexamined
One mechanism through which migraine increases the risk of stroke is the constriction of blood vessels, said Louis R. Caplan, MD, professor of neurology at Harvard Medical School in Boston and member of the editorial advisory board of Neurology Reviews. Triptans, which many patients use to treat migraine, also cause vasoconstriction. In addition, migraine increases blood coagulation.
Although the risk score developed by Dr. Sen and colleagues accounts for various comorbidities, it may not apply equally to all patients. “As I understand it, they’re just using migraine with aura as a single factor,” said Dr. Caplan. Variables such as prolonged aura, frequent episodes, and aura-related deficit are associated with increased risk of stroke, but the risk score does not examine these factors.
Patients with severe, long-lasting attacks or attacks that involve weakness or aphasia should receive prophylactic treatment to prevent vasoconstriction, such as verapamil (Verelan), said Dr. Caplan. Antithrombotic agents such as aspirin also may be appropriate prophylaxis. Whether effective treatment of migraine with aura decreases the risk of stroke remains unknown.
SOURCE: Trivedi T et al. ISC 2020. Abstract WMP117.
REPORTING FROM ISC 2020
AUGUSTUS: Apixaban surpassed warfarin despite prior stroke or thromboembolism
LOS ANGELES – The edge that the direct-acting oral anticoagulant apixaban (Eliquis) has over warfarin for safely preventing ischemic events in patients with atrial fibrillation and either a recent acute coronary syndrome event or a recent percutaneous coronary intervention held up even in patients with a history of stroke, transient ischemic attack, or thromboembolic event, according to a prespecified secondary analysis of data collected in the AUGUSTUS trial.
The treatment advantages of apixaban, compared with warfarin, seen in the overall AUGUSTUS results, first reported in March 2019, “were consistent” with the benefits seen in the subgroup of enrolled patients with a prior stroke, transient ischemic attack (TIA), or thromboembolic (TE) event, M. Cecilia Bahit, MD, said at the International Stroke Conference sponsored by the American Heart Association.
All patients in AUGUSTUS received a P2Y12 inhibitor antiplatelet drug, which was clopidogrel for more than 90% of patients. The two-by-two factorial design of AUGUSTUS also assessed the safety and efficacy of either adding or withholding aspirin from the two-drug regimen that all patients in the study received with a P2Y12 inhibitor plus an anticoagulant (apixaban or warfarin). The most notable finding of the aspirin versus placebo analysis was that patients without a prior stroke, TIA, or TE event had a “more profound” increase in their rate of major or clinically relevant minor bleeds when also treated with aspirin, compared with patients who received aspirin and had a history of stroke, TIA, or TE event, reported Dr. Bahit, a chief of cardiology and director of clinical research at the INECO Foundation in Rosario, Argentina.
[embed:link:node:196616]
In general, the findings of the secondary analysis that took into account stroke, TIA, or TE history “confirmed” the main AUGUSTUS findings, Dr. Bahit said; an antithrombotic regimen of apixaban plus clopidogrel (or other P2Y12 inhibitor) without aspirin was superior for both efficacy and safety, compared with the alternative regimens that either substituted warfarin for apixaban or that added aspirin.
AUGUSTUS enrolled 4,614 atrial fibrillation (AFib) patients who either had a recent acute coronary syndrome (ACS) event or had recently undergone percutaneous coronary intervention (PCI) at any of 492 sites in 33 countries during 2015-2018. The study’s primary endpoint was the incidence of major or clinically relevant minor bleeds after 6 months, which was significantly lower in the subgroups that received apixaban instead of warfarin and in patients who received placebo instead of aspirin. The secondary endpoint of death or hospitalization after 6 months was also significantly lower in the apixaban-treated patients, compared with those on warfarin, while the aspirin and placebo subgroups showed no difference in the incidence of these events (N Engl J Med. 2019 Apr 18;380[16]:1509-24).
The results reported by Dr. Bahit also highlighted both the high risk faced by patients with AFib who also have had an ACS event or PCI, as well as a prior stroke, TIA, or TE event, noted Larry B. Goldstein, MD, professor and chairman of neurology at the University of Kentucky, Lexington. “It’s difficult, because these patients had an ACS event or PCI, and you don’t want a coronary too close up, but do these patients really need a P2Y12 inhibitor plus an anticoagulant? Could these patients do as well on apixaban only? I would have liked to see that treatment arm in the study,” Dr. Goldstein commented in an interview.
“These are challenging patients because they often require anticoagulation for the AFib as well as antiplatelet agents” for the recent PCI or ACS event, commented Mitchell S.V. Elkind, MD, professor of neurology at Columbia University, New York. “The question has always been: How many blood thinners should these patients be on? Potentially they could be on three different agents [an anticoagulant and two antiplatelet drugs], and we know that all of those drugs together pretty dramatically increase the risk of bleeding. About 15% of the patients in the overall AUGUSTUS trial had either cerebrovascular disease or systemic thromboembolism, so this was a small subgroup of the overall trial, but the overall trial was large so it’s a significant number of patients who met this criteria. The results confirmed that even in a group of patients who may be considered at high risk because they have a prior history of cerebrovascular disease use of apixaban instead of warfarin seemed safer, and that those patients did not need to be on aspirin as well as their other antiplatelet agent. Patients with a history of stroke, in fact, had a lower risk of bleeding than the other patients in this trial, so one could argue that they should be on an agent like apixaban as well as an antiplatelet agent like clopidogrel without addition of aspirin,” he said in a recorded statement.
In addition to implications for using prescription drugs like apixaban and clopidogrel, the findings also send a message about the need for very aggressive implementation of lifestyle measures that can reduce cardiovascular disease risk in these patients, added Dr. Goldstein. The AUGUSTUS outcome analyses that subdivided the study population into those with a prior stroke, TIA, or TE event – 633 patients or about 14% of the 4,581 patients eligible for this analysis – and those who did not have this history showed the extremely high, incrementally elevated risk faced by patients with these prior events.
A history of stroke, TIA, or TE event linked with a jump in the 90-day rate of major or clinically relevant minor bleeds from 13% without this history to 17%, which is a 31% relative increase; it boosted the 90-day rate of death or hospitalization from 25% to 31%, a 24% relative increase; and it jacked up the rate of death or ischemic events from 6% to 9%, a 50% relative increase, Dr. Bahit reported.
These substantial increases “suggest we need to be very aggressive” in managing these high-risk patients who combine a background of AFib, a prior stroke, TIA, or TE events, and a recent ACS event or PCI, Dr. Goldstein observed. In these patients, he suggested that clinicians make sure to address smoking cessation, obesity, exercise, diet, and statin use, and get each of these to an optimal level to further cut risk. If all five of these basic interventions were successfully administered to a patient they could collectively cut the patient’s event risk by about 80%, he added.
AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer, the companies that jointly market apixaban. Dr. Bahit has received honoraria from Pfizer, and from CSL Behring and Merck. Dr. Elkind and Dr. Goldstein had no relevant disclosures.
SOURCE: Bahit MC et al. ISC 2020, Abstract LB22.
LOS ANGELES – The edge that the direct-acting oral anticoagulant apixaban (Eliquis) has over warfarin for safely preventing ischemic events in patients with atrial fibrillation and either a recent acute coronary syndrome event or a recent percutaneous coronary intervention held up even in patients with a history of stroke, transient ischemic attack, or thromboembolic event, according to a prespecified secondary analysis of data collected in the AUGUSTUS trial.
The treatment advantages of apixaban, compared with warfarin, seen in the overall AUGUSTUS results, first reported in March 2019, “were consistent” with the benefits seen in the subgroup of enrolled patients with a prior stroke, transient ischemic attack (TIA), or thromboembolic (TE) event, M. Cecilia Bahit, MD, said at the International Stroke Conference sponsored by the American Heart Association.
All patients in AUGUSTUS received a P2Y12 inhibitor antiplatelet drug, which was clopidogrel for more than 90% of patients. The two-by-two factorial design of AUGUSTUS also assessed the safety and efficacy of either adding or withholding aspirin from the two-drug regimen that all patients in the study received with a P2Y12 inhibitor plus an anticoagulant (apixaban or warfarin). The most notable finding of the aspirin versus placebo analysis was that patients without a prior stroke, TIA, or TE event had a “more profound” increase in their rate of major or clinically relevant minor bleeds when also treated with aspirin, compared with patients who received aspirin and had a history of stroke, TIA, or TE event, reported Dr. Bahit, a chief of cardiology and director of clinical research at the INECO Foundation in Rosario, Argentina.
[embed:link:node:196616]
In general, the findings of the secondary analysis that took into account stroke, TIA, or TE history “confirmed” the main AUGUSTUS findings, Dr. Bahit said; an antithrombotic regimen of apixaban plus clopidogrel (or other P2Y12 inhibitor) without aspirin was superior for both efficacy and safety, compared with the alternative regimens that either substituted warfarin for apixaban or that added aspirin.
AUGUSTUS enrolled 4,614 atrial fibrillation (AFib) patients who either had a recent acute coronary syndrome (ACS) event or had recently undergone percutaneous coronary intervention (PCI) at any of 492 sites in 33 countries during 2015-2018. The study’s primary endpoint was the incidence of major or clinically relevant minor bleeds after 6 months, which was significantly lower in the subgroups that received apixaban instead of warfarin and in patients who received placebo instead of aspirin. The secondary endpoint of death or hospitalization after 6 months was also significantly lower in the apixaban-treated patients, compared with those on warfarin, while the aspirin and placebo subgroups showed no difference in the incidence of these events (N Engl J Med. 2019 Apr 18;380[16]:1509-24).
The results reported by Dr. Bahit also highlighted both the high risk faced by patients with AFib who also have had an ACS event or PCI, as well as a prior stroke, TIA, or TE event, noted Larry B. Goldstein, MD, professor and chairman of neurology at the University of Kentucky, Lexington. “It’s difficult, because these patients had an ACS event or PCI, and you don’t want a coronary too close up, but do these patients really need a P2Y12 inhibitor plus an anticoagulant? Could these patients do as well on apixaban only? I would have liked to see that treatment arm in the study,” Dr. Goldstein commented in an interview.
“These are challenging patients because they often require anticoagulation for the AFib as well as antiplatelet agents” for the recent PCI or ACS event, commented Mitchell S.V. Elkind, MD, professor of neurology at Columbia University, New York. “The question has always been: How many blood thinners should these patients be on? Potentially they could be on three different agents [an anticoagulant and two antiplatelet drugs], and we know that all of those drugs together pretty dramatically increase the risk of bleeding. About 15% of the patients in the overall AUGUSTUS trial had either cerebrovascular disease or systemic thromboembolism, so this was a small subgroup of the overall trial, but the overall trial was large so it’s a significant number of patients who met this criteria. The results confirmed that even in a group of patients who may be considered at high risk because they have a prior history of cerebrovascular disease use of apixaban instead of warfarin seemed safer, and that those patients did not need to be on aspirin as well as their other antiplatelet agent. Patients with a history of stroke, in fact, had a lower risk of bleeding than the other patients in this trial, so one could argue that they should be on an agent like apixaban as well as an antiplatelet agent like clopidogrel without addition of aspirin,” he said in a recorded statement.
In addition to implications for using prescription drugs like apixaban and clopidogrel, the findings also send a message about the need for very aggressive implementation of lifestyle measures that can reduce cardiovascular disease risk in these patients, added Dr. Goldstein. The AUGUSTUS outcome analyses that subdivided the study population into those with a prior stroke, TIA, or TE event – 633 patients or about 14% of the 4,581 patients eligible for this analysis – and those who did not have this history showed the extremely high, incrementally elevated risk faced by patients with these prior events.
A history of stroke, TIA, or TE event linked with a jump in the 90-day rate of major or clinically relevant minor bleeds from 13% without this history to 17%, which is a 31% relative increase; it boosted the 90-day rate of death or hospitalization from 25% to 31%, a 24% relative increase; and it jacked up the rate of death or ischemic events from 6% to 9%, a 50% relative increase, Dr. Bahit reported.
These substantial increases “suggest we need to be very aggressive” in managing these high-risk patients who combine a background of AFib, a prior stroke, TIA, or TE events, and a recent ACS event or PCI, Dr. Goldstein observed. In these patients, he suggested that clinicians make sure to address smoking cessation, obesity, exercise, diet, and statin use, and get each of these to an optimal level to further cut risk. If all five of these basic interventions were successfully administered to a patient they could collectively cut the patient’s event risk by about 80%, he added.
AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer, the companies that jointly market apixaban. Dr. Bahit has received honoraria from Pfizer, and from CSL Behring and Merck. Dr. Elkind and Dr. Goldstein had no relevant disclosures.
SOURCE: Bahit MC et al. ISC 2020, Abstract LB22.
LOS ANGELES – The edge that the direct-acting oral anticoagulant apixaban (Eliquis) has over warfarin for safely preventing ischemic events in patients with atrial fibrillation and either a recent acute coronary syndrome event or a recent percutaneous coronary intervention held up even in patients with a history of stroke, transient ischemic attack, or thromboembolic event, according to a prespecified secondary analysis of data collected in the AUGUSTUS trial.
The treatment advantages of apixaban, compared with warfarin, seen in the overall AUGUSTUS results, first reported in March 2019, “were consistent” with the benefits seen in the subgroup of enrolled patients with a prior stroke, transient ischemic attack (TIA), or thromboembolic (TE) event, M. Cecilia Bahit, MD, said at the International Stroke Conference sponsored by the American Heart Association.
All patients in AUGUSTUS received a P2Y12 inhibitor antiplatelet drug, which was clopidogrel for more than 90% of patients. The two-by-two factorial design of AUGUSTUS also assessed the safety and efficacy of either adding or withholding aspirin from the two-drug regimen that all patients in the study received with a P2Y12 inhibitor plus an anticoagulant (apixaban or warfarin). The most notable finding of the aspirin versus placebo analysis was that patients without a prior stroke, TIA, or TE event had a “more profound” increase in their rate of major or clinically relevant minor bleeds when also treated with aspirin, compared with patients who received aspirin and had a history of stroke, TIA, or TE event, reported Dr. Bahit, a chief of cardiology and director of clinical research at the INECO Foundation in Rosario, Argentina.
[embed:link:node:196616]
In general, the findings of the secondary analysis that took into account stroke, TIA, or TE history “confirmed” the main AUGUSTUS findings, Dr. Bahit said; an antithrombotic regimen of apixaban plus clopidogrel (or other P2Y12 inhibitor) without aspirin was superior for both efficacy and safety, compared with the alternative regimens that either substituted warfarin for apixaban or that added aspirin.
AUGUSTUS enrolled 4,614 atrial fibrillation (AFib) patients who either had a recent acute coronary syndrome (ACS) event or had recently undergone percutaneous coronary intervention (PCI) at any of 492 sites in 33 countries during 2015-2018. The study’s primary endpoint was the incidence of major or clinically relevant minor bleeds after 6 months, which was significantly lower in the subgroups that received apixaban instead of warfarin and in patients who received placebo instead of aspirin. The secondary endpoint of death or hospitalization after 6 months was also significantly lower in the apixaban-treated patients, compared with those on warfarin, while the aspirin and placebo subgroups showed no difference in the incidence of these events (N Engl J Med. 2019 Apr 18;380[16]:1509-24).
The results reported by Dr. Bahit also highlighted both the high risk faced by patients with AFib who also have had an ACS event or PCI, as well as a prior stroke, TIA, or TE event, noted Larry B. Goldstein, MD, professor and chairman of neurology at the University of Kentucky, Lexington. “It’s difficult, because these patients had an ACS event or PCI, and you don’t want a coronary too close up, but do these patients really need a P2Y12 inhibitor plus an anticoagulant? Could these patients do as well on apixaban only? I would have liked to see that treatment arm in the study,” Dr. Goldstein commented in an interview.
“These are challenging patients because they often require anticoagulation for the AFib as well as antiplatelet agents” for the recent PCI or ACS event, commented Mitchell S.V. Elkind, MD, professor of neurology at Columbia University, New York. “The question has always been: How many blood thinners should these patients be on? Potentially they could be on three different agents [an anticoagulant and two antiplatelet drugs], and we know that all of those drugs together pretty dramatically increase the risk of bleeding. About 15% of the patients in the overall AUGUSTUS trial had either cerebrovascular disease or systemic thromboembolism, so this was a small subgroup of the overall trial, but the overall trial was large so it’s a significant number of patients who met this criteria. The results confirmed that even in a group of patients who may be considered at high risk because they have a prior history of cerebrovascular disease use of apixaban instead of warfarin seemed safer, and that those patients did not need to be on aspirin as well as their other antiplatelet agent. Patients with a history of stroke, in fact, had a lower risk of bleeding than the other patients in this trial, so one could argue that they should be on an agent like apixaban as well as an antiplatelet agent like clopidogrel without addition of aspirin,” he said in a recorded statement.
In addition to implications for using prescription drugs like apixaban and clopidogrel, the findings also send a message about the need for very aggressive implementation of lifestyle measures that can reduce cardiovascular disease risk in these patients, added Dr. Goldstein. The AUGUSTUS outcome analyses that subdivided the study population into those with a prior stroke, TIA, or TE event – 633 patients or about 14% of the 4,581 patients eligible for this analysis – and those who did not have this history showed the extremely high, incrementally elevated risk faced by patients with these prior events.
A history of stroke, TIA, or TE event linked with a jump in the 90-day rate of major or clinically relevant minor bleeds from 13% without this history to 17%, which is a 31% relative increase; it boosted the 90-day rate of death or hospitalization from 25% to 31%, a 24% relative increase; and it jacked up the rate of death or ischemic events from 6% to 9%, a 50% relative increase, Dr. Bahit reported.
These substantial increases “suggest we need to be very aggressive” in managing these high-risk patients who combine a background of AFib, a prior stroke, TIA, or TE events, and a recent ACS event or PCI, Dr. Goldstein observed. In these patients, he suggested that clinicians make sure to address smoking cessation, obesity, exercise, diet, and statin use, and get each of these to an optimal level to further cut risk. If all five of these basic interventions were successfully administered to a patient they could collectively cut the patient’s event risk by about 80%, he added.
AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer, the companies that jointly market apixaban. Dr. Bahit has received honoraria from Pfizer, and from CSL Behring and Merck. Dr. Elkind and Dr. Goldstein had no relevant disclosures.
SOURCE: Bahit MC et al. ISC 2020, Abstract LB22.
REPORTING FROM ISC 2020
AFib patients do best on a DOAC started 7-10 days post stroke
LOS ANGELES – When a patient with atrial fibrillation (AFib) has a cardioembolic stroke, the best blood thinner to start may be a direct-acting oral anticoagulant (DOAC), possibly beginning 7-10 days after the index stroke, according to an analysis of 90-day, observational outcomes data from nearly 1,300 patients.
The analysis also suggested that the use of “bridging” anticoagulant treatment by injection before a patient with atrial fibrillation (AFib) starts a daily oral anticoagulant regimen following a cardioembolic stroke is not a good idea. Patients who received bridging anticoagulation had a nearly threefold higher rate of symptomatic intracranial hemorrhage than did patients who did not, and their bridging treatment failed to protect them from recurrent ischemic events, Shadi Yaghi, MD, said at the International Stroke Conference, sponsored by the American Heart Association. The bridging regimens delivered either heparin or low-molecular-weight heparin.
Based on the findings, “it seems reasonable to avoid bridging unless absolutely necessary, to initiate a DOAC unless it’s contraindicated, and to start the DOAC on day 7-10 following the stroke in most patients,” said Dr. Yaghi, a vascular neurologist and director of stroke research at NYU Langone Health in New York.
“It’s been hard to develop a broad guideline on when to start oral anticoagulation” after a cardioembolic stroke in AFib patients. The best time “depends on a lot of variables and how the patient responded to acute treatment,” commented Alexis Simpkins, MD, a vascular and stroke neurologist at the University of Florida in Gainesville. “You want to start treatment before the patient has another stroke, but not so soon that the treatment causes symptomatic hemorrhagic transformation.”
Dr. Yaghi’s suggestion, based on his findings, to start treatment for most patients with a DOAC 7-10 days after their index stroke “shows consistency” with the prevailing guideline recommendation from the AHA/American Stroke Association to start oral anticoagulation in this patient population 4-14 days after the index stroke (Stroke. 2018 March;49[3]:e46-e99), she noted.
A recent article reviewed the uncertainty about the best time to start oral anticoagulation in AFib patients after a cardioembolic stroke and the subtle differences that distinguish various international medical groups that, like the ASA, have made recommendations (Lancet Neurol. 2019 Jan 1;18[1]:117-26). According to this review, a major limitation of these various recommendations has been the lack of actual evidence collected from AFib patients who began receiving a DOAC shortly after a cardioembolic stroke, although the article added that several studies in progress are collecting these data.
The study reported by Dr. Yaghi pooled data collected from 2,084 recent AFib patients with a cardioembolic stroke treated at any of eight comprehensive U.S. stroke centers. They excluded patients who died from causes unrelated to the primary endpoint, those who did not receive an anticoagulant or had incomplete data, and patients lost to follow-up, leaving 1,289 evaluable patients. During their 90-day follow-up, 10% of the patients had an ischemic event, a symptomatic intracranial hemorrhage, or an extracranial hemorrhage.
The study’s primary analysis showed no statistically significant difference in the incidence of recurrent ischemic events, symptomatic intracranial hemorrhage, or both based on when oral anticoagulant treatment began: 0-3 days, 4-14 days, or more than 14 days after the index stroke.
[embed:render:related:node:202317]
The investigators then subdivided patients into the subgroup that started treatment with a DOAC and the subgroup that started treatment with warfarin and also further subdivided the 4-14 day time window for starting treatment. Results of this analysis showed that patients who received a DOAC and began this treatment 7-10 days after their stroke had a 50% cut in their 90-day events compared with other patients, a difference that fell just short of statistical significance at P = .07. All the other combinations of oral anticoagulant and time of treatment initiation analyzed showed neutral effects that never came near statistical significance.
Secondary data analyses also showed that both patients with a history of a stroke prior to their index stroke and patients with ipsilateral atherosclerosis came close to having a statistically significant increased rate of a subsequent ischemic event during 90-day follow-up. Furthermore, women, patients with a history of hyperlipidemia, and patients who developed hemorrhagic transformation of their index stroke all had significantly increased rates of developing a symptomatic intracranial hemorrhage during 90-day follow-up. When the endpoint was limited to recurrent ischemic events only, patients who received a DOAC were 50% less likely to have an event than were patients treated with warfarin, a statistically significant difference.
Although starting a DOAC 7-10 days after the index stroke seems reasonable based on this analysis, the question needs a prospective, randomized study to create an appropriate evidence base, Dr. Yaghi said.
Dr. Yaghi disclosed a financial relationship with Medtronic. Dr. Simpkins had no disclosures.
SOURCE: Yaghi S et al. Stroke. 2020 Feb;51(suppl 1):A119.
LOS ANGELES – When a patient with atrial fibrillation (AFib) has a cardioembolic stroke, the best blood thinner to start may be a direct-acting oral anticoagulant (DOAC), possibly beginning 7-10 days after the index stroke, according to an analysis of 90-day, observational outcomes data from nearly 1,300 patients.
The analysis also suggested that the use of “bridging” anticoagulant treatment by injection before a patient with atrial fibrillation (AFib) starts a daily oral anticoagulant regimen following a cardioembolic stroke is not a good idea. Patients who received bridging anticoagulation had a nearly threefold higher rate of symptomatic intracranial hemorrhage than did patients who did not, and their bridging treatment failed to protect them from recurrent ischemic events, Shadi Yaghi, MD, said at the International Stroke Conference, sponsored by the American Heart Association. The bridging regimens delivered either heparin or low-molecular-weight heparin.
Based on the findings, “it seems reasonable to avoid bridging unless absolutely necessary, to initiate a DOAC unless it’s contraindicated, and to start the DOAC on day 7-10 following the stroke in most patients,” said Dr. Yaghi, a vascular neurologist and director of stroke research at NYU Langone Health in New York.
“It’s been hard to develop a broad guideline on when to start oral anticoagulation” after a cardioembolic stroke in AFib patients. The best time “depends on a lot of variables and how the patient responded to acute treatment,” commented Alexis Simpkins, MD, a vascular and stroke neurologist at the University of Florida in Gainesville. “You want to start treatment before the patient has another stroke, but not so soon that the treatment causes symptomatic hemorrhagic transformation.”
Dr. Yaghi’s suggestion, based on his findings, to start treatment for most patients with a DOAC 7-10 days after their index stroke “shows consistency” with the prevailing guideline recommendation from the AHA/American Stroke Association to start oral anticoagulation in this patient population 4-14 days after the index stroke (Stroke. 2018 March;49[3]:e46-e99), she noted.
A recent article reviewed the uncertainty about the best time to start oral anticoagulation in AFib patients after a cardioembolic stroke and the subtle differences that distinguish various international medical groups that, like the ASA, have made recommendations (Lancet Neurol. 2019 Jan 1;18[1]:117-26). According to this review, a major limitation of these various recommendations has been the lack of actual evidence collected from AFib patients who began receiving a DOAC shortly after a cardioembolic stroke, although the article added that several studies in progress are collecting these data.
The study reported by Dr. Yaghi pooled data collected from 2,084 recent AFib patients with a cardioembolic stroke treated at any of eight comprehensive U.S. stroke centers. They excluded patients who died from causes unrelated to the primary endpoint, those who did not receive an anticoagulant or had incomplete data, and patients lost to follow-up, leaving 1,289 evaluable patients. During their 90-day follow-up, 10% of the patients had an ischemic event, a symptomatic intracranial hemorrhage, or an extracranial hemorrhage.
The study’s primary analysis showed no statistically significant difference in the incidence of recurrent ischemic events, symptomatic intracranial hemorrhage, or both based on when oral anticoagulant treatment began: 0-3 days, 4-14 days, or more than 14 days after the index stroke.
[embed:render:related:node:202317]
The investigators then subdivided patients into the subgroup that started treatment with a DOAC and the subgroup that started treatment with warfarin and also further subdivided the 4-14 day time window for starting treatment. Results of this analysis showed that patients who received a DOAC and began this treatment 7-10 days after their stroke had a 50% cut in their 90-day events compared with other patients, a difference that fell just short of statistical significance at P = .07. All the other combinations of oral anticoagulant and time of treatment initiation analyzed showed neutral effects that never came near statistical significance.
Secondary data analyses also showed that both patients with a history of a stroke prior to their index stroke and patients with ipsilateral atherosclerosis came close to having a statistically significant increased rate of a subsequent ischemic event during 90-day follow-up. Furthermore, women, patients with a history of hyperlipidemia, and patients who developed hemorrhagic transformation of their index stroke all had significantly increased rates of developing a symptomatic intracranial hemorrhage during 90-day follow-up. When the endpoint was limited to recurrent ischemic events only, patients who received a DOAC were 50% less likely to have an event than were patients treated with warfarin, a statistically significant difference.
Although starting a DOAC 7-10 days after the index stroke seems reasonable based on this analysis, the question needs a prospective, randomized study to create an appropriate evidence base, Dr. Yaghi said.
Dr. Yaghi disclosed a financial relationship with Medtronic. Dr. Simpkins had no disclosures.
SOURCE: Yaghi S et al. Stroke. 2020 Feb;51(suppl 1):A119.
LOS ANGELES – When a patient with atrial fibrillation (AFib) has a cardioembolic stroke, the best blood thinner to start may be a direct-acting oral anticoagulant (DOAC), possibly beginning 7-10 days after the index stroke, according to an analysis of 90-day, observational outcomes data from nearly 1,300 patients.
The analysis also suggested that the use of “bridging” anticoagulant treatment by injection before a patient with atrial fibrillation (AFib) starts a daily oral anticoagulant regimen following a cardioembolic stroke is not a good idea. Patients who received bridging anticoagulation had a nearly threefold higher rate of symptomatic intracranial hemorrhage than did patients who did not, and their bridging treatment failed to protect them from recurrent ischemic events, Shadi Yaghi, MD, said at the International Stroke Conference, sponsored by the American Heart Association. The bridging regimens delivered either heparin or low-molecular-weight heparin.
Based on the findings, “it seems reasonable to avoid bridging unless absolutely necessary, to initiate a DOAC unless it’s contraindicated, and to start the DOAC on day 7-10 following the stroke in most patients,” said Dr. Yaghi, a vascular neurologist and director of stroke research at NYU Langone Health in New York.
“It’s been hard to develop a broad guideline on when to start oral anticoagulation” after a cardioembolic stroke in AFib patients. The best time “depends on a lot of variables and how the patient responded to acute treatment,” commented Alexis Simpkins, MD, a vascular and stroke neurologist at the University of Florida in Gainesville. “You want to start treatment before the patient has another stroke, but not so soon that the treatment causes symptomatic hemorrhagic transformation.”
Dr. Yaghi’s suggestion, based on his findings, to start treatment for most patients with a DOAC 7-10 days after their index stroke “shows consistency” with the prevailing guideline recommendation from the AHA/American Stroke Association to start oral anticoagulation in this patient population 4-14 days after the index stroke (Stroke. 2018 March;49[3]:e46-e99), she noted.
A recent article reviewed the uncertainty about the best time to start oral anticoagulation in AFib patients after a cardioembolic stroke and the subtle differences that distinguish various international medical groups that, like the ASA, have made recommendations (Lancet Neurol. 2019 Jan 1;18[1]:117-26). According to this review, a major limitation of these various recommendations has been the lack of actual evidence collected from AFib patients who began receiving a DOAC shortly after a cardioembolic stroke, although the article added that several studies in progress are collecting these data.
The study reported by Dr. Yaghi pooled data collected from 2,084 recent AFib patients with a cardioembolic stroke treated at any of eight comprehensive U.S. stroke centers. They excluded patients who died from causes unrelated to the primary endpoint, those who did not receive an anticoagulant or had incomplete data, and patients lost to follow-up, leaving 1,289 evaluable patients. During their 90-day follow-up, 10% of the patients had an ischemic event, a symptomatic intracranial hemorrhage, or an extracranial hemorrhage.
The study’s primary analysis showed no statistically significant difference in the incidence of recurrent ischemic events, symptomatic intracranial hemorrhage, or both based on when oral anticoagulant treatment began: 0-3 days, 4-14 days, or more than 14 days after the index stroke.
[embed:render:related:node:202317]
The investigators then subdivided patients into the subgroup that started treatment with a DOAC and the subgroup that started treatment with warfarin and also further subdivided the 4-14 day time window for starting treatment. Results of this analysis showed that patients who received a DOAC and began this treatment 7-10 days after their stroke had a 50% cut in their 90-day events compared with other patients, a difference that fell just short of statistical significance at P = .07. All the other combinations of oral anticoagulant and time of treatment initiation analyzed showed neutral effects that never came near statistical significance.
Secondary data analyses also showed that both patients with a history of a stroke prior to their index stroke and patients with ipsilateral atherosclerosis came close to having a statistically significant increased rate of a subsequent ischemic event during 90-day follow-up. Furthermore, women, patients with a history of hyperlipidemia, and patients who developed hemorrhagic transformation of their index stroke all had significantly increased rates of developing a symptomatic intracranial hemorrhage during 90-day follow-up. When the endpoint was limited to recurrent ischemic events only, patients who received a DOAC were 50% less likely to have an event than were patients treated with warfarin, a statistically significant difference.
Although starting a DOAC 7-10 days after the index stroke seems reasonable based on this analysis, the question needs a prospective, randomized study to create an appropriate evidence base, Dr. Yaghi said.
Dr. Yaghi disclosed a financial relationship with Medtronic. Dr. Simpkins had no disclosures.
SOURCE: Yaghi S et al. Stroke. 2020 Feb;51(suppl 1):A119.
REPORTING FROM ISC 2020
DAPT may benefit symptomatic carotid endarterectomy patients
LOS ANGELES –
The only patients who benefited from postsurgical treatment with dual antiplatelet therapy (DAPT) were those who were symptomatic (had a stroke or transient ischemic attack) prior to their carotid endarterectomy surgery, a minority of the more than 17,000 matched U.S. patients who underwent carotid endarterectomy during 2003-2018 and were part of this analysis, Nathan Belkin, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
Among patients with symptoms prior to their carotid endarterectomy, DAPT at the time of hospital discharge was associated with a 2-year follow-up rate of stroke, transient ischemic attack (TIA), or death of about 8%, compared with a rate of about 11% among similar patients discharged on aspirin only, a statistically significant difference. In contrast, among patients who were asymptomatic prior to their carotid endarterectomy, discharge treatment with aspirin only was associated with a 2-year event rate similar to the rate among patients discharged on DAPT.
Based in part on this finding, Dr. Belkin and associates at the University of Pennsylvania, Philadelphia, now start symptomatic patients scheduled for carotid endarterectomy on DAPT with aspirin plus clopidogrel (Plavix) about 2 weeks before surgery, and then continue the combined regimen long term after surgery. A prospective, randomized study is needed to fully resolve the optimal use of DAPT in patients with significant carotid artery disease scheduled for carotid endarterectomy, but until then, “we’re individualizing DAPT” to patients at high risk because of a prior stroke or TIA who also have no evidence of an elevated bleeding risk, said Dr. Belkin, a vascular surgeon.
“We hypothesize that patients with systemic carotid disease have a systemic disease process and more activated platelets,” which suggests a potential benefit from DAPT, he explained. But the data that Dr. Belkin reported also indicated that recent U.S. use of DAPT in patients undergoing carotid endarterectomy has moved beyond this subgroup. The U.S. national data set that Dr. Belkin used for the analysis, the Vascular Quality Initiative registry maintained by the Society for Vascular Surgery, included 87,074 patients who underwent carotid endarterectomy during 2003-2018. During the entire 16-year period, 30% of patients overall received a prescription for DAPT at hospital discharge, but this level went steadily up during those years. In 2003, the rate of DAPT prescriptions at discharge was below 10% of patients but then rose incrementally over the following years and by 2018 had increased to about 44% despite a prevalence of symptomatic carotid disease closer to about a third of patients.
“It’s surprising that so many patients received DAPT for carotid disease” in recent years, commented Mai N. Nguyen-Huynh, MD, a vascular neurologist with Kaiser Permanente Northern California in Oakland. “It’s been thought that DAPT, and especially clopidogrel, was more beneficial for patients with intracranial atherosclerotic disease, but not so much for patients with carotid disease,” she said in an interview. “We don’t always see systemic atherosclerotic disease in patients with carotid artery disease. It’s not standard practice to look for systemic atherosclerotic disease in patients with carotid disease,” unless something in the patient’s presentation suggests wider vascular-disease progression.
The primary analysis that Dr. Belkin and associates ran removed about 16% of the patients who underwent carotid endarterectomy from the database: those who received no antiplatelet drug, those who received only clopidogrel, and those who went home from surgery on an anticoagulant. Among the remaining 72,122 patients, 35% received DAPT at discharge and 65% received aspirin only. The patients averaged 70 years old, 61% were men, 37% had a history of stroke or TIA, and their overall 2-year incidence of stroke, TIA, or death was 7.3%. To adjust for many baseline differences between the patients discharged on DAPT and those who got only aspirin, the researchers used propensity-score sorting to identify 17,398 matched patients from the two treatment subgroups, 24% of the total population. Comparison of these DAPT and aspirin-only subgroups showed no difference in the overall, 2-year rate of stroke, TIA, or death.
[embed:render:related:node:209032]
However, when the analysis divided the patients into asymptomatic and symptomatic subgroups, those discharged on DAPT showed a statistically significant lower rate of stroke, TIA, or death during 2 years of follow-up. The same symptomatic subgroup also showed a statistically significant lower rate of total mortality during 5 years of follow-up when treated with DAPT compared with aspirin only, again an absolute, between-group difference of about 3 percentage points that was statistically significant, a difference not seen in the asymptomatic patients. The type of treatment that symptomatic patients received had no relationship to their 2-year incidence of stroke or TIA.
To confirm these findings, Dr. Belkin and coworkers ran a multivariate logistic regression analysis on the data collected from all 72,122 patients who underwent carotid endarterectomy and subsequently received either DAPT or aspirin only. The only statistically significant association between treatment and outcome was among the symptomatic patients who received DAPT, who had a significant reduction in their 5-year mortality, compared with symptomatic patients who received only aspirin at hospital discharge.
Ideally, a comparison of DAPT and aspirin-only treatment should also assess the incidence and severity of bleeding events associated with these treatments, but bleeding data were not available in the database, Dr. Belkin said.
Dr. Belkin and Dr. Nguyen-Huynh had no relevant disclosures.
SOURCE: Belkin N et al. Stroke. 2020 Feb;51(suppl 1): Abstract 67.
LOS ANGELES –
The only patients who benefited from postsurgical treatment with dual antiplatelet therapy (DAPT) were those who were symptomatic (had a stroke or transient ischemic attack) prior to their carotid endarterectomy surgery, a minority of the more than 17,000 matched U.S. patients who underwent carotid endarterectomy during 2003-2018 and were part of this analysis, Nathan Belkin, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
Among patients with symptoms prior to their carotid endarterectomy, DAPT at the time of hospital discharge was associated with a 2-year follow-up rate of stroke, transient ischemic attack (TIA), or death of about 8%, compared with a rate of about 11% among similar patients discharged on aspirin only, a statistically significant difference. In contrast, among patients who were asymptomatic prior to their carotid endarterectomy, discharge treatment with aspirin only was associated with a 2-year event rate similar to the rate among patients discharged on DAPT.
Based in part on this finding, Dr. Belkin and associates at the University of Pennsylvania, Philadelphia, now start symptomatic patients scheduled for carotid endarterectomy on DAPT with aspirin plus clopidogrel (Plavix) about 2 weeks before surgery, and then continue the combined regimen long term after surgery. A prospective, randomized study is needed to fully resolve the optimal use of DAPT in patients with significant carotid artery disease scheduled for carotid endarterectomy, but until then, “we’re individualizing DAPT” to patients at high risk because of a prior stroke or TIA who also have no evidence of an elevated bleeding risk, said Dr. Belkin, a vascular surgeon.
“We hypothesize that patients with systemic carotid disease have a systemic disease process and more activated platelets,” which suggests a potential benefit from DAPT, he explained. But the data that Dr. Belkin reported also indicated that recent U.S. use of DAPT in patients undergoing carotid endarterectomy has moved beyond this subgroup. The U.S. national data set that Dr. Belkin used for the analysis, the Vascular Quality Initiative registry maintained by the Society for Vascular Surgery, included 87,074 patients who underwent carotid endarterectomy during 2003-2018. During the entire 16-year period, 30% of patients overall received a prescription for DAPT at hospital discharge, but this level went steadily up during those years. In 2003, the rate of DAPT prescriptions at discharge was below 10% of patients but then rose incrementally over the following years and by 2018 had increased to about 44% despite a prevalence of symptomatic carotid disease closer to about a third of patients.
“It’s surprising that so many patients received DAPT for carotid disease” in recent years, commented Mai N. Nguyen-Huynh, MD, a vascular neurologist with Kaiser Permanente Northern California in Oakland. “It’s been thought that DAPT, and especially clopidogrel, was more beneficial for patients with intracranial atherosclerotic disease, but not so much for patients with carotid disease,” she said in an interview. “We don’t always see systemic atherosclerotic disease in patients with carotid artery disease. It’s not standard practice to look for systemic atherosclerotic disease in patients with carotid disease,” unless something in the patient’s presentation suggests wider vascular-disease progression.
The primary analysis that Dr. Belkin and associates ran removed about 16% of the patients who underwent carotid endarterectomy from the database: those who received no antiplatelet drug, those who received only clopidogrel, and those who went home from surgery on an anticoagulant. Among the remaining 72,122 patients, 35% received DAPT at discharge and 65% received aspirin only. The patients averaged 70 years old, 61% were men, 37% had a history of stroke or TIA, and their overall 2-year incidence of stroke, TIA, or death was 7.3%. To adjust for many baseline differences between the patients discharged on DAPT and those who got only aspirin, the researchers used propensity-score sorting to identify 17,398 matched patients from the two treatment subgroups, 24% of the total population. Comparison of these DAPT and aspirin-only subgroups showed no difference in the overall, 2-year rate of stroke, TIA, or death.
[embed:render:related:node:209032]
However, when the analysis divided the patients into asymptomatic and symptomatic subgroups, those discharged on DAPT showed a statistically significant lower rate of stroke, TIA, or death during 2 years of follow-up. The same symptomatic subgroup also showed a statistically significant lower rate of total mortality during 5 years of follow-up when treated with DAPT compared with aspirin only, again an absolute, between-group difference of about 3 percentage points that was statistically significant, a difference not seen in the asymptomatic patients. The type of treatment that symptomatic patients received had no relationship to their 2-year incidence of stroke or TIA.
To confirm these findings, Dr. Belkin and coworkers ran a multivariate logistic regression analysis on the data collected from all 72,122 patients who underwent carotid endarterectomy and subsequently received either DAPT or aspirin only. The only statistically significant association between treatment and outcome was among the symptomatic patients who received DAPT, who had a significant reduction in their 5-year mortality, compared with symptomatic patients who received only aspirin at hospital discharge.
Ideally, a comparison of DAPT and aspirin-only treatment should also assess the incidence and severity of bleeding events associated with these treatments, but bleeding data were not available in the database, Dr. Belkin said.
Dr. Belkin and Dr. Nguyen-Huynh had no relevant disclosures.
SOURCE: Belkin N et al. Stroke. 2020 Feb;51(suppl 1): Abstract 67.
LOS ANGELES –
The only patients who benefited from postsurgical treatment with dual antiplatelet therapy (DAPT) were those who were symptomatic (had a stroke or transient ischemic attack) prior to their carotid endarterectomy surgery, a minority of the more than 17,000 matched U.S. patients who underwent carotid endarterectomy during 2003-2018 and were part of this analysis, Nathan Belkin, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
Among patients with symptoms prior to their carotid endarterectomy, DAPT at the time of hospital discharge was associated with a 2-year follow-up rate of stroke, transient ischemic attack (TIA), or death of about 8%, compared with a rate of about 11% among similar patients discharged on aspirin only, a statistically significant difference. In contrast, among patients who were asymptomatic prior to their carotid endarterectomy, discharge treatment with aspirin only was associated with a 2-year event rate similar to the rate among patients discharged on DAPT.
Based in part on this finding, Dr. Belkin and associates at the University of Pennsylvania, Philadelphia, now start symptomatic patients scheduled for carotid endarterectomy on DAPT with aspirin plus clopidogrel (Plavix) about 2 weeks before surgery, and then continue the combined regimen long term after surgery. A prospective, randomized study is needed to fully resolve the optimal use of DAPT in patients with significant carotid artery disease scheduled for carotid endarterectomy, but until then, “we’re individualizing DAPT” to patients at high risk because of a prior stroke or TIA who also have no evidence of an elevated bleeding risk, said Dr. Belkin, a vascular surgeon.
“We hypothesize that patients with systemic carotid disease have a systemic disease process and more activated platelets,” which suggests a potential benefit from DAPT, he explained. But the data that Dr. Belkin reported also indicated that recent U.S. use of DAPT in patients undergoing carotid endarterectomy has moved beyond this subgroup. The U.S. national data set that Dr. Belkin used for the analysis, the Vascular Quality Initiative registry maintained by the Society for Vascular Surgery, included 87,074 patients who underwent carotid endarterectomy during 2003-2018. During the entire 16-year period, 30% of patients overall received a prescription for DAPT at hospital discharge, but this level went steadily up during those years. In 2003, the rate of DAPT prescriptions at discharge was below 10% of patients but then rose incrementally over the following years and by 2018 had increased to about 44% despite a prevalence of symptomatic carotid disease closer to about a third of patients.
“It’s surprising that so many patients received DAPT for carotid disease” in recent years, commented Mai N. Nguyen-Huynh, MD, a vascular neurologist with Kaiser Permanente Northern California in Oakland. “It’s been thought that DAPT, and especially clopidogrel, was more beneficial for patients with intracranial atherosclerotic disease, but not so much for patients with carotid disease,” she said in an interview. “We don’t always see systemic atherosclerotic disease in patients with carotid artery disease. It’s not standard practice to look for systemic atherosclerotic disease in patients with carotid disease,” unless something in the patient’s presentation suggests wider vascular-disease progression.
The primary analysis that Dr. Belkin and associates ran removed about 16% of the patients who underwent carotid endarterectomy from the database: those who received no antiplatelet drug, those who received only clopidogrel, and those who went home from surgery on an anticoagulant. Among the remaining 72,122 patients, 35% received DAPT at discharge and 65% received aspirin only. The patients averaged 70 years old, 61% were men, 37% had a history of stroke or TIA, and their overall 2-year incidence of stroke, TIA, or death was 7.3%. To adjust for many baseline differences between the patients discharged on DAPT and those who got only aspirin, the researchers used propensity-score sorting to identify 17,398 matched patients from the two treatment subgroups, 24% of the total population. Comparison of these DAPT and aspirin-only subgroups showed no difference in the overall, 2-year rate of stroke, TIA, or death.
[embed:render:related:node:209032]
However, when the analysis divided the patients into asymptomatic and symptomatic subgroups, those discharged on DAPT showed a statistically significant lower rate of stroke, TIA, or death during 2 years of follow-up. The same symptomatic subgroup also showed a statistically significant lower rate of total mortality during 5 years of follow-up when treated with DAPT compared with aspirin only, again an absolute, between-group difference of about 3 percentage points that was statistically significant, a difference not seen in the asymptomatic patients. The type of treatment that symptomatic patients received had no relationship to their 2-year incidence of stroke or TIA.
To confirm these findings, Dr. Belkin and coworkers ran a multivariate logistic regression analysis on the data collected from all 72,122 patients who underwent carotid endarterectomy and subsequently received either DAPT or aspirin only. The only statistically significant association between treatment and outcome was among the symptomatic patients who received DAPT, who had a significant reduction in their 5-year mortality, compared with symptomatic patients who received only aspirin at hospital discharge.
Ideally, a comparison of DAPT and aspirin-only treatment should also assess the incidence and severity of bleeding events associated with these treatments, but bleeding data were not available in the database, Dr. Belkin said.
Dr. Belkin and Dr. Nguyen-Huynh had no relevant disclosures.
SOURCE: Belkin N et al. Stroke. 2020 Feb;51(suppl 1): Abstract 67.
REPORTING FROM ISC 2020
Transradial access gains converts among U.S. interventional neurologists
LOS ANGELES –
“It’s growing dramatically in U.S. practice. It may be hype, but there is big excitement. We are still in an assessment mode, but the adoption rate has been high,” Raul G. Nogueira, MD, said in an interview during the International Stroke Conference sponsored by the American Heart Association. “The big advantage [of transradial catheterization entry] is elimination of groin complications, some of which can be pretty bad. Is it safe for the brain? It’s probably okay, but that needs more study,” said Dr. Nogueira, professor of neurology at Emory University and director of the Neurovascular Service at the Grady Marcus Stroke and Neuroscience Center in Atlanta.
His uncertainty stems from the more difficult route taken to advance a catheter from the wrist into brain vessels, a maneuver that requires significant manipulation of the catheter tip, unlike the path from the right radial artery into the heart’s arteries, a “straight shot,” he explained. To reach the brain’s vasculature, the tip must execute a spin “that may scrape small emboli from the arch or arteries, so we need to look at this a little more carefully.” Ideally in a prospective, randomized study, he said. “We need to see whether the burden of [magnetic resonance] lesions is any higher when you go through the radial [artery].”
Some of the first-reported, large-scale U.S. experiences using a radial-artery approach for various neurovascular procedures, including a few thrombectomy cases, came in a series of 1,272 patients treated at any of four U.S. centers during July 2018 to June 2019, a period when the neurovascular staffs at all four centers transitioned from primarily using femoral-artery access to using radial access as their default mode. During the 12-month transition period, overall use of radial access at all four centers rose from roughly a quarter of all neurovascular interventions during July to September 2018 to closer to 80% by April to June 2019, Eyad Almallouhi, MD, reported at the conference.
[embed:render:related:node:198104]
During the entire 12 months, the operators ran up a 94% rate of successfully completed procedures using radial access, a rate that rose from about 88% during the first quarter to roughly 95% success during the fourth quarter tracked, said Dr. Almallouhi, a neurologist at the Medical University of South Carolina in Charleston. The rate of crossover from what began as a transradial procedure but switched to transfemoral was just under 6% overall, with a nearly 14% crossover rate during the first quarter that then dropped to around 5% for the rest of the transition year. Crossovers for interventional procedures throughout the study year occurred at a 12% rate, while crossovers for diagnostic procedures occurred at a 5% clip throughout the entire year.
None of the transradial patients had a major access-site complication, and minor complications occurred in less than 2% of the patients, including 11 with a forearm hematoma, 6 with forearm pain, and 5 with oozing at their access site. The absence of any major access-site complications among the transradial-access patients in this series contrasts with a recent report of a 1.7% rate of major complications secondary to femoral-artery access for mechanical thrombectomy in a combined analysis of data from seven published studies that included 660 thrombectomy procedures (Am J Neuroradiol. 2019 Feb. doi: 10.3174/ajnr.A6423). The other three centers that participated in the study Dr. Almallouhi presented were the University of Miami, Thomas Jefferson University in Philadelphia, and the University of Pittsburgh.
Of the 1,272 total procedures studied, 83% were diagnostic procedures, which had an overall 95% success rate, and 17% were interventional procedures, which had a success rate of 89%. The interventional transradial procedures included 62 primary coilings of aneurysms, 44 stent-assisted aneurysm coilings, 40 patients who underwent a flow diversion, 21 balloon-assisted aneurysm coilings, and 24 patients who underwent stroke thrombectomy.
The size of the devices commonly used for thrombectomy are often too large to allow for radial-artery access, noted Dr. Nogueira. For urgent interventions like thrombectomy “we use balloon-guided catheters that are large-bore and don’t fit well in the radial,” he said, although thrombectomy via the radial artery without a balloon-guided catheter is possible for clots located in the basilar artery. Last year, researchers in Germany reported using a balloon-guided catheter to perform mechanical thrombectomy via the radial artery (Interv Neuroradiol. 2019 Oct 1;25[5]:508-10). But it’s a different story for elective, diagnostic procedures. “I have moved most of these to transradial,” Dr. Nogueira said. He and his coauthors summarized the case for transradial access for cerebral angiography in a recent review; in addition to enhanced safety they cited other advantages including improved patient satisfaction and reduced cost because of a shorter length of stay (Interv Cardiol Clin. 2020 Jan;9[1]:75-86).
Despite his enthusiasm and the enthusiasm of other neurointerventionalists for the transradial approach, other stroke neurologists have been more cautious and slower to shift away from the femoral approach. “Our experience has been that for most cases it’s a bit more challenging to access the cervical vessels from the radial artery than from the traditional femoral approach. For arches with complex anatomy, however, the transradial approach can be of benefit in some cases, depending on the angles that need to be traversed,” commented Jeremy Payne, MD, director of the Banner Center for Neurovascular Medicine and medical director of the Banner—University Medical Center Phoenix Comprehensive Stroke Program. Dr. Payne highlighted that, while he is not an interventionalist himself, he and his interventional staff have regularly discussed the transradial option.
“In the cardiology literature the radial approach has been very successful, with better overall safety than the traditional femoral approach. Largely this seems to do with the anatomy of the aortic arch. It’s simply a more direct approach to the coronaries via the right radial artery; getting the wire into the correct vessel is significantly more difficult the more acute the angle it has to traverse,” such as when the target is an intracerebral vessel, Dr. Payne said in an interview.
“Our experience in the past 6 months has been about 25% transradial for some of our procedures, mainly diagnostic angiograms. We don’t find any difference in safety, however, as our transfemoral procedures are already very safe. One of the benefits of a transradial approach has been that a closure device may not be needed, with fewer vascular complications at the access site, such as fistula formation. We use ultrasound for access, and have not seen a difference in those approaches at all so far. One might argue that using ultrasound to establish access would slow us down, but so far our fastest case start-to-recanalization time in an acute stroke this year was 6 minutes, so speed does not appear to be a limiting issue. Another concern overall for transradial access is the potential limitation in the tools we may be able to deploy, given the smaller size of the vessel. It is reassuring [in the report from Dr. Almallouhi] that a variety of cases were successfully completed via this approach. However, fewer than 2% of their cases [24 patients] were apparently emergent, acute strokes, lending no specific support to that context. I do not expect that to change based on this paper,” Dr. Payne concluded.
“It is not clear to me that transradial neurointervention will change much. We have excellent safety data for the femoral approach, a proven track record of efficacy, and for most patients it seems to afford a somewhat wider range of tools that can be deployed, with simpler anatomy for accessing the cervical vessels in most arches. It is reassuring that the results reported by Dr. Almallouhi did not suggest negative outcomes, and as such I suspect the transradial approach at least gives us an additional option in a minority of patients. We have seen in the past 5-10 years an explosion of tools for the endovascular treatment of stroke; transradial access represents another potential strategy that appears so far to be safe,” Dr. Payne said.
Drs. Nogueira, Almallouhi, and Payne had no relevant disclosures.
SOURCE: Almallouhi E et al. Stroke. 2020 Feb;51(suppl 1):A64.
LOS ANGELES –
“It’s growing dramatically in U.S. practice. It may be hype, but there is big excitement. We are still in an assessment mode, but the adoption rate has been high,” Raul G. Nogueira, MD, said in an interview during the International Stroke Conference sponsored by the American Heart Association. “The big advantage [of transradial catheterization entry] is elimination of groin complications, some of which can be pretty bad. Is it safe for the brain? It’s probably okay, but that needs more study,” said Dr. Nogueira, professor of neurology at Emory University and director of the Neurovascular Service at the Grady Marcus Stroke and Neuroscience Center in Atlanta.
His uncertainty stems from the more difficult route taken to advance a catheter from the wrist into brain vessels, a maneuver that requires significant manipulation of the catheter tip, unlike the path from the right radial artery into the heart’s arteries, a “straight shot,” he explained. To reach the brain’s vasculature, the tip must execute a spin “that may scrape small emboli from the arch or arteries, so we need to look at this a little more carefully.” Ideally in a prospective, randomized study, he said. “We need to see whether the burden of [magnetic resonance] lesions is any higher when you go through the radial [artery].”
Some of the first-reported, large-scale U.S. experiences using a radial-artery approach for various neurovascular procedures, including a few thrombectomy cases, came in a series of 1,272 patients treated at any of four U.S. centers during July 2018 to June 2019, a period when the neurovascular staffs at all four centers transitioned from primarily using femoral-artery access to using radial access as their default mode. During the 12-month transition period, overall use of radial access at all four centers rose from roughly a quarter of all neurovascular interventions during July to September 2018 to closer to 80% by April to June 2019, Eyad Almallouhi, MD, reported at the conference.
[embed:render:related:node:198104]
During the entire 12 months, the operators ran up a 94% rate of successfully completed procedures using radial access, a rate that rose from about 88% during the first quarter to roughly 95% success during the fourth quarter tracked, said Dr. Almallouhi, a neurologist at the Medical University of South Carolina in Charleston. The rate of crossover from what began as a transradial procedure but switched to transfemoral was just under 6% overall, with a nearly 14% crossover rate during the first quarter that then dropped to around 5% for the rest of the transition year. Crossovers for interventional procedures throughout the study year occurred at a 12% rate, while crossovers for diagnostic procedures occurred at a 5% clip throughout the entire year.
None of the transradial patients had a major access-site complication, and minor complications occurred in less than 2% of the patients, including 11 with a forearm hematoma, 6 with forearm pain, and 5 with oozing at their access site. The absence of any major access-site complications among the transradial-access patients in this series contrasts with a recent report of a 1.7% rate of major complications secondary to femoral-artery access for mechanical thrombectomy in a combined analysis of data from seven published studies that included 660 thrombectomy procedures (Am J Neuroradiol. 2019 Feb. doi: 10.3174/ajnr.A6423). The other three centers that participated in the study Dr. Almallouhi presented were the University of Miami, Thomas Jefferson University in Philadelphia, and the University of Pittsburgh.
Of the 1,272 total procedures studied, 83% were diagnostic procedures, which had an overall 95% success rate, and 17% were interventional procedures, which had a success rate of 89%. The interventional transradial procedures included 62 primary coilings of aneurysms, 44 stent-assisted aneurysm coilings, 40 patients who underwent a flow diversion, 21 balloon-assisted aneurysm coilings, and 24 patients who underwent stroke thrombectomy.
The size of the devices commonly used for thrombectomy are often too large to allow for radial-artery access, noted Dr. Nogueira. For urgent interventions like thrombectomy “we use balloon-guided catheters that are large-bore and don’t fit well in the radial,” he said, although thrombectomy via the radial artery without a balloon-guided catheter is possible for clots located in the basilar artery. Last year, researchers in Germany reported using a balloon-guided catheter to perform mechanical thrombectomy via the radial artery (Interv Neuroradiol. 2019 Oct 1;25[5]:508-10). But it’s a different story for elective, diagnostic procedures. “I have moved most of these to transradial,” Dr. Nogueira said. He and his coauthors summarized the case for transradial access for cerebral angiography in a recent review; in addition to enhanced safety they cited other advantages including improved patient satisfaction and reduced cost because of a shorter length of stay (Interv Cardiol Clin. 2020 Jan;9[1]:75-86).
Despite his enthusiasm and the enthusiasm of other neurointerventionalists for the transradial approach, other stroke neurologists have been more cautious and slower to shift away from the femoral approach. “Our experience has been that for most cases it’s a bit more challenging to access the cervical vessels from the radial artery than from the traditional femoral approach. For arches with complex anatomy, however, the transradial approach can be of benefit in some cases, depending on the angles that need to be traversed,” commented Jeremy Payne, MD, director of the Banner Center for Neurovascular Medicine and medical director of the Banner—University Medical Center Phoenix Comprehensive Stroke Program. Dr. Payne highlighted that, while he is not an interventionalist himself, he and his interventional staff have regularly discussed the transradial option.
“In the cardiology literature the radial approach has been very successful, with better overall safety than the traditional femoral approach. Largely this seems to do with the anatomy of the aortic arch. It’s simply a more direct approach to the coronaries via the right radial artery; getting the wire into the correct vessel is significantly more difficult the more acute the angle it has to traverse,” such as when the target is an intracerebral vessel, Dr. Payne said in an interview.
“Our experience in the past 6 months has been about 25% transradial for some of our procedures, mainly diagnostic angiograms. We don’t find any difference in safety, however, as our transfemoral procedures are already very safe. One of the benefits of a transradial approach has been that a closure device may not be needed, with fewer vascular complications at the access site, such as fistula formation. We use ultrasound for access, and have not seen a difference in those approaches at all so far. One might argue that using ultrasound to establish access would slow us down, but so far our fastest case start-to-recanalization time in an acute stroke this year was 6 minutes, so speed does not appear to be a limiting issue. Another concern overall for transradial access is the potential limitation in the tools we may be able to deploy, given the smaller size of the vessel. It is reassuring [in the report from Dr. Almallouhi] that a variety of cases were successfully completed via this approach. However, fewer than 2% of their cases [24 patients] were apparently emergent, acute strokes, lending no specific support to that context. I do not expect that to change based on this paper,” Dr. Payne concluded.
“It is not clear to me that transradial neurointervention will change much. We have excellent safety data for the femoral approach, a proven track record of efficacy, and for most patients it seems to afford a somewhat wider range of tools that can be deployed, with simpler anatomy for accessing the cervical vessels in most arches. It is reassuring that the results reported by Dr. Almallouhi did not suggest negative outcomes, and as such I suspect the transradial approach at least gives us an additional option in a minority of patients. We have seen in the past 5-10 years an explosion of tools for the endovascular treatment of stroke; transradial access represents another potential strategy that appears so far to be safe,” Dr. Payne said.
Drs. Nogueira, Almallouhi, and Payne had no relevant disclosures.
SOURCE: Almallouhi E et al. Stroke. 2020 Feb;51(suppl 1):A64.
LOS ANGELES –
“It’s growing dramatically in U.S. practice. It may be hype, but there is big excitement. We are still in an assessment mode, but the adoption rate has been high,” Raul G. Nogueira, MD, said in an interview during the International Stroke Conference sponsored by the American Heart Association. “The big advantage [of transradial catheterization entry] is elimination of groin complications, some of which can be pretty bad. Is it safe for the brain? It’s probably okay, but that needs more study,” said Dr. Nogueira, professor of neurology at Emory University and director of the Neurovascular Service at the Grady Marcus Stroke and Neuroscience Center in Atlanta.
His uncertainty stems from the more difficult route taken to advance a catheter from the wrist into brain vessels, a maneuver that requires significant manipulation of the catheter tip, unlike the path from the right radial artery into the heart’s arteries, a “straight shot,” he explained. To reach the brain’s vasculature, the tip must execute a spin “that may scrape small emboli from the arch or arteries, so we need to look at this a little more carefully.” Ideally in a prospective, randomized study, he said. “We need to see whether the burden of [magnetic resonance] lesions is any higher when you go through the radial [artery].”
Some of the first-reported, large-scale U.S. experiences using a radial-artery approach for various neurovascular procedures, including a few thrombectomy cases, came in a series of 1,272 patients treated at any of four U.S. centers during July 2018 to June 2019, a period when the neurovascular staffs at all four centers transitioned from primarily using femoral-artery access to using radial access as their default mode. During the 12-month transition period, overall use of radial access at all four centers rose from roughly a quarter of all neurovascular interventions during July to September 2018 to closer to 80% by April to June 2019, Eyad Almallouhi, MD, reported at the conference.
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During the entire 12 months, the operators ran up a 94% rate of successfully completed procedures using radial access, a rate that rose from about 88% during the first quarter to roughly 95% success during the fourth quarter tracked, said Dr. Almallouhi, a neurologist at the Medical University of South Carolina in Charleston. The rate of crossover from what began as a transradial procedure but switched to transfemoral was just under 6% overall, with a nearly 14% crossover rate during the first quarter that then dropped to around 5% for the rest of the transition year. Crossovers for interventional procedures throughout the study year occurred at a 12% rate, while crossovers for diagnostic procedures occurred at a 5% clip throughout the entire year.
None of the transradial patients had a major access-site complication, and minor complications occurred in less than 2% of the patients, including 11 with a forearm hematoma, 6 with forearm pain, and 5 with oozing at their access site. The absence of any major access-site complications among the transradial-access patients in this series contrasts with a recent report of a 1.7% rate of major complications secondary to femoral-artery access for mechanical thrombectomy in a combined analysis of data from seven published studies that included 660 thrombectomy procedures (Am J Neuroradiol. 2019 Feb. doi: 10.3174/ajnr.A6423). The other three centers that participated in the study Dr. Almallouhi presented were the University of Miami, Thomas Jefferson University in Philadelphia, and the University of Pittsburgh.
Of the 1,272 total procedures studied, 83% were diagnostic procedures, which had an overall 95% success rate, and 17% were interventional procedures, which had a success rate of 89%. The interventional transradial procedures included 62 primary coilings of aneurysms, 44 stent-assisted aneurysm coilings, 40 patients who underwent a flow diversion, 21 balloon-assisted aneurysm coilings, and 24 patients who underwent stroke thrombectomy.
The size of the devices commonly used for thrombectomy are often too large to allow for radial-artery access, noted Dr. Nogueira. For urgent interventions like thrombectomy “we use balloon-guided catheters that are large-bore and don’t fit well in the radial,” he said, although thrombectomy via the radial artery without a balloon-guided catheter is possible for clots located in the basilar artery. Last year, researchers in Germany reported using a balloon-guided catheter to perform mechanical thrombectomy via the radial artery (Interv Neuroradiol. 2019 Oct 1;25[5]:508-10). But it’s a different story for elective, diagnostic procedures. “I have moved most of these to transradial,” Dr. Nogueira said. He and his coauthors summarized the case for transradial access for cerebral angiography in a recent review; in addition to enhanced safety they cited other advantages including improved patient satisfaction and reduced cost because of a shorter length of stay (Interv Cardiol Clin. 2020 Jan;9[1]:75-86).
Despite his enthusiasm and the enthusiasm of other neurointerventionalists for the transradial approach, other stroke neurologists have been more cautious and slower to shift away from the femoral approach. “Our experience has been that for most cases it’s a bit more challenging to access the cervical vessels from the radial artery than from the traditional femoral approach. For arches with complex anatomy, however, the transradial approach can be of benefit in some cases, depending on the angles that need to be traversed,” commented Jeremy Payne, MD, director of the Banner Center for Neurovascular Medicine and medical director of the Banner—University Medical Center Phoenix Comprehensive Stroke Program. Dr. Payne highlighted that, while he is not an interventionalist himself, he and his interventional staff have regularly discussed the transradial option.
“In the cardiology literature the radial approach has been very successful, with better overall safety than the traditional femoral approach. Largely this seems to do with the anatomy of the aortic arch. It’s simply a more direct approach to the coronaries via the right radial artery; getting the wire into the correct vessel is significantly more difficult the more acute the angle it has to traverse,” such as when the target is an intracerebral vessel, Dr. Payne said in an interview.
“Our experience in the past 6 months has been about 25% transradial for some of our procedures, mainly diagnostic angiograms. We don’t find any difference in safety, however, as our transfemoral procedures are already very safe. One of the benefits of a transradial approach has been that a closure device may not be needed, with fewer vascular complications at the access site, such as fistula formation. We use ultrasound for access, and have not seen a difference in those approaches at all so far. One might argue that using ultrasound to establish access would slow us down, but so far our fastest case start-to-recanalization time in an acute stroke this year was 6 minutes, so speed does not appear to be a limiting issue. Another concern overall for transradial access is the potential limitation in the tools we may be able to deploy, given the smaller size of the vessel. It is reassuring [in the report from Dr. Almallouhi] that a variety of cases were successfully completed via this approach. However, fewer than 2% of their cases [24 patients] were apparently emergent, acute strokes, lending no specific support to that context. I do not expect that to change based on this paper,” Dr. Payne concluded.
“It is not clear to me that transradial neurointervention will change much. We have excellent safety data for the femoral approach, a proven track record of efficacy, and for most patients it seems to afford a somewhat wider range of tools that can be deployed, with simpler anatomy for accessing the cervical vessels in most arches. It is reassuring that the results reported by Dr. Almallouhi did not suggest negative outcomes, and as such I suspect the transradial approach at least gives us an additional option in a minority of patients. We have seen in the past 5-10 years an explosion of tools for the endovascular treatment of stroke; transradial access represents another potential strategy that appears so far to be safe,” Dr. Payne said.
Drs. Nogueira, Almallouhi, and Payne had no relevant disclosures.
SOURCE: Almallouhi E et al. Stroke. 2020 Feb;51(suppl 1):A64.
REPORTING FROM ISC 2020
More evidence backs LDL below 70 to reduce recurrent stroke
LOS ANGELES – In a subanalysis of the TST (Treat Stroke to Target) trial, restricting analysis to only French participants followed for an average of 5 years demonstrated an even more robust potential to reduce recurrent stroke and other major cardiovascular events by treating patients to an LDL target of below 70 mg/dL. Treating LDL to a mean of 66 mg/dL versus 96 mg/dL was associated with a 26% relative risk reduction for the composite endpoint of ischemic stroke, MI, new symptoms requiring urgent coronary or carotid revascularization, and vascular death in an adjusted analysis.
“The results are similar to the main paper but even more spectacular, with no increase in hemorrhagic stroke whatsoever, and positive results on any stroke,” study investigator Pierre Amarenco, MD, professor and chair of the department of neurology and Stroke Centre, Bichat University Hospital, Paris, said.
Dr. Amarenco presented the findings as a late-breaking abstract at the International Stroke Conference sponsored by the American Heart Association. The trial was published simultaneously in the journal Stroke.
In the full TST trial population, risk was reduced by 22% with more-aggressive LDL-lowering treatment, compared with the more lax 90-110 mg/dL target.
The TST cohort included both French and Korean participants. Dr. Amarenco and colleagues focused on the French population in the current study because the group was larger (2,148 vs. 742 Korean participants) and had a longer follow-up, an average of 5.3 years compared to 2.0 years among Korean patients. The initial study had shown “very significant results in the French patients and no apparent effect in Korean patients,” he said. The longer duration of treatment in the French cohort could have contributed to the greater risk reduction, said Dr. Amarenco.
A 2017 European Atherosclerosis Society Consensus Panel statement noted that exposure time to lipid-lowering drugs correlates with outcomes. The European Stroke Organization and the American Heart Association/American Stroke Association guidelines each recommend intensive statin treatment to lower serum lipids following an ischemic stroke of atherosclerotic origin or after a transient ischemic attack (TIA). However, the current researchers noted that the recommendations do not specify specific target numbers.
“Therefore, there is uncertainty about the target levels of LDL cholesterol,” he said.
Aiming at different targets
To learn more, Dr. Amarenco and colleagues randomly assigned 1,073 of the French patients to a target LDL treatment group of 70 mg/dL and another 1,075 to a target range of 90-110 mg/dL. They enrolled participants at 61 sites in France. Mean age was 67 years. All participants had experienced an ischemic stroke within 3 months or a TIA within 15 days of baseline. They presented either with a modified Rankin Scale poststroke score of 0-3 or a TIA that included at least arm and leg motor deficit or speech disturbance that lasted more than 10 minutes.
Investigators could use any type and any dose of statin to reach the respective targets. Statins could be prescribed as monotherapy or in combination with ezetimibe (Zetia) or other agents. The baseline mean LDL cholesterol level was 137 mg/dL in the lower target group and 138 mg/dL in the higher target group, respectively (3.5 mmol/L in both groups). Dr. Amarenco and colleagues measured LDL cholesterol levels at 3 weeks postrandomization and then every 6 months.
A smaller proportion of the lower LDL cholesterol target group experienced the adverse composite outcome, 9.6%, compared with 12.9% of the higher LDL cholesterol target group. This translated to a hazard ratio of 0.73 (95% confidence interval, 0.57-0.94; P = .015). The absolute risk reduction was 3.3% with a number needed to treat of 30.
An analysis adjusted for covariates showed a hazard ratio of 0.74 (95% CI, 0.57-0.95; P = .019).
Cerebral infarction and acute cerebral artery revascularization were reduced by 27% (HR, 0.73; 95% CI, 0.54-0.99; P = .046). Cerebral infarction or intracranial hemorrhage (all strokes) were reduced by 28% (HR, 0.72; 95% CI, 0.54-0.98; P = .023). In this case, there was an absolute risk reduction of 2.9% and a number needed to treat of 34.
In contrast, MI or urgent coronary revascularization following new symptoms were not significantly reduced (HR, 0.66; 95% CI, 0.67-1.20; P = .18). The investigators also reported nonsignificant results regarding vascular death (HR, 0.76; 95% CI, 0.44-1.32; P = .32] and all deaths (HR, 1.0; 95% CI, 0.74-1.35; P = .99).
Dr. Amarenco and colleagues also tracked adverse events. They found intracranial hemorrhage occurred in 13 (1.2%) patients assigned an LDL cholesterol below 70 mg/dL and in 11 (1%) patients assigned an LDL cholesterol of 100 ± 10 mg/dL. In this analysis, the hazard ratio was 1.17 (95% CI, 0.53-2.62; P = .70), and the absolute difference was 0.2%.
The investigators also reported that 10.3% of the lower LDL target group vs 13.6% of the higher LDL target group experienced either the primary outcome or intracranial hemorrhage. This translated to a 25% relative risk reduction (HR, 0.75; 95% CI, 0.58-0.96; P = .021), an absolute risk reduction of 3.3% and a number needed to treat of 30.
Avoiding one in four events
Assessing the French participants in the TST trial showed that targeting LDL below 70 mg/dL for more than 5 years avoided more than one in four subsequent major cardiovascular events among adults who experienced a recent ischemic stroke or TIA.
Furthermore, more intense LDL lowering also avoided more than one in four recurrent cerebral infarctions or urgent carotid revascularizations following a TIA, as well as one in four recurrent cerebral infarctions or hemorrhages (all strokes), compared with the higher LDL target.
“This was obtained without increasing the risk of intracranial hemorrhage with a number needed to treat of 30,” the researchers noted. “In the context of all randomized clinical trials with statin and other lipid-lowering drugs, there is no reason to think that Asian patients do not benefit from statin treatment and from a lower target LDL cholesterol,” the researchers added.
Therefore, they plan to continue assessing the 742 Korean participants until they reach a median of 5 years of follow-up.
Clinically validating results
“My feeling is that these data are highly supportive of a practice that many of us have been using for years without this level of evidence,” Mitchell S.V. Elkind, MD, said when asked to comment on the study.
Prior secondary analyses of studies, including research into patients with intracranial atherosclerosis, demonstrated benefit from treating to this lower LDL cholesterol target. “These studies were suggestive enough that many of us were treating patients aggressively with statins,” added Dr. Elkind, professor of neurology and epidemiology and chief of the division of neurology clinical outcomes research and population sciences at Columbia University in New York.
“But this really confirms that [fact] with clinical trial evidence,” said Dr. Elkind, “and I think will be very useful to us as clinicians.”
The results could be used to counsel patients about the potential benefits of statin therapy or to motivate primary care providers to treat patients more aggressively, said Dr. Elkind, who will begin his term as president of the American Heart Association/American Stroke Association in July.
This study was supported by a grant from the French Ministry of Health and from SOS-Attaque Cérébrale Association, with unrestricted grants from Pfizer, AstraZeneca, and Merck for French sites and from Pfizer for South Korean sites.
Dr. Amarenco receives research grant support and consulting fees from Pfizer, Merck, and AstraZeneca. Elkind had has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SOURCE: Amarenko P et al. ISC 2020. Late-breaking abstract 9.
LOS ANGELES – In a subanalysis of the TST (Treat Stroke to Target) trial, restricting analysis to only French participants followed for an average of 5 years demonstrated an even more robust potential to reduce recurrent stroke and other major cardiovascular events by treating patients to an LDL target of below 70 mg/dL. Treating LDL to a mean of 66 mg/dL versus 96 mg/dL was associated with a 26% relative risk reduction for the composite endpoint of ischemic stroke, MI, new symptoms requiring urgent coronary or carotid revascularization, and vascular death in an adjusted analysis.
“The results are similar to the main paper but even more spectacular, with no increase in hemorrhagic stroke whatsoever, and positive results on any stroke,” study investigator Pierre Amarenco, MD, professor and chair of the department of neurology and Stroke Centre, Bichat University Hospital, Paris, said.
Dr. Amarenco presented the findings as a late-breaking abstract at the International Stroke Conference sponsored by the American Heart Association. The trial was published simultaneously in the journal Stroke.
In the full TST trial population, risk was reduced by 22% with more-aggressive LDL-lowering treatment, compared with the more lax 90-110 mg/dL target.
The TST cohort included both French and Korean participants. Dr. Amarenco and colleagues focused on the French population in the current study because the group was larger (2,148 vs. 742 Korean participants) and had a longer follow-up, an average of 5.3 years compared to 2.0 years among Korean patients. The initial study had shown “very significant results in the French patients and no apparent effect in Korean patients,” he said. The longer duration of treatment in the French cohort could have contributed to the greater risk reduction, said Dr. Amarenco.
A 2017 European Atherosclerosis Society Consensus Panel statement noted that exposure time to lipid-lowering drugs correlates with outcomes. The European Stroke Organization and the American Heart Association/American Stroke Association guidelines each recommend intensive statin treatment to lower serum lipids following an ischemic stroke of atherosclerotic origin or after a transient ischemic attack (TIA). However, the current researchers noted that the recommendations do not specify specific target numbers.
“Therefore, there is uncertainty about the target levels of LDL cholesterol,” he said.
Aiming at different targets
To learn more, Dr. Amarenco and colleagues randomly assigned 1,073 of the French patients to a target LDL treatment group of 70 mg/dL and another 1,075 to a target range of 90-110 mg/dL. They enrolled participants at 61 sites in France. Mean age was 67 years. All participants had experienced an ischemic stroke within 3 months or a TIA within 15 days of baseline. They presented either with a modified Rankin Scale poststroke score of 0-3 or a TIA that included at least arm and leg motor deficit or speech disturbance that lasted more than 10 minutes.
Investigators could use any type and any dose of statin to reach the respective targets. Statins could be prescribed as monotherapy or in combination with ezetimibe (Zetia) or other agents. The baseline mean LDL cholesterol level was 137 mg/dL in the lower target group and 138 mg/dL in the higher target group, respectively (3.5 mmol/L in both groups). Dr. Amarenco and colleagues measured LDL cholesterol levels at 3 weeks postrandomization and then every 6 months.
A smaller proportion of the lower LDL cholesterol target group experienced the adverse composite outcome, 9.6%, compared with 12.9% of the higher LDL cholesterol target group. This translated to a hazard ratio of 0.73 (95% confidence interval, 0.57-0.94; P = .015). The absolute risk reduction was 3.3% with a number needed to treat of 30.
An analysis adjusted for covariates showed a hazard ratio of 0.74 (95% CI, 0.57-0.95; P = .019).
Cerebral infarction and acute cerebral artery revascularization were reduced by 27% (HR, 0.73; 95% CI, 0.54-0.99; P = .046). Cerebral infarction or intracranial hemorrhage (all strokes) were reduced by 28% (HR, 0.72; 95% CI, 0.54-0.98; P = .023). In this case, there was an absolute risk reduction of 2.9% and a number needed to treat of 34.
In contrast, MI or urgent coronary revascularization following new symptoms were not significantly reduced (HR, 0.66; 95% CI, 0.67-1.20; P = .18). The investigators also reported nonsignificant results regarding vascular death (HR, 0.76; 95% CI, 0.44-1.32; P = .32] and all deaths (HR, 1.0; 95% CI, 0.74-1.35; P = .99).
Dr. Amarenco and colleagues also tracked adverse events. They found intracranial hemorrhage occurred in 13 (1.2%) patients assigned an LDL cholesterol below 70 mg/dL and in 11 (1%) patients assigned an LDL cholesterol of 100 ± 10 mg/dL. In this analysis, the hazard ratio was 1.17 (95% CI, 0.53-2.62; P = .70), and the absolute difference was 0.2%.
The investigators also reported that 10.3% of the lower LDL target group vs 13.6% of the higher LDL target group experienced either the primary outcome or intracranial hemorrhage. This translated to a 25% relative risk reduction (HR, 0.75; 95% CI, 0.58-0.96; P = .021), an absolute risk reduction of 3.3% and a number needed to treat of 30.
Avoiding one in four events
Assessing the French participants in the TST trial showed that targeting LDL below 70 mg/dL for more than 5 years avoided more than one in four subsequent major cardiovascular events among adults who experienced a recent ischemic stroke or TIA.
Furthermore, more intense LDL lowering also avoided more than one in four recurrent cerebral infarctions or urgent carotid revascularizations following a TIA, as well as one in four recurrent cerebral infarctions or hemorrhages (all strokes), compared with the higher LDL target.
“This was obtained without increasing the risk of intracranial hemorrhage with a number needed to treat of 30,” the researchers noted. “In the context of all randomized clinical trials with statin and other lipid-lowering drugs, there is no reason to think that Asian patients do not benefit from statin treatment and from a lower target LDL cholesterol,” the researchers added.
Therefore, they plan to continue assessing the 742 Korean participants until they reach a median of 5 years of follow-up.
Clinically validating results
“My feeling is that these data are highly supportive of a practice that many of us have been using for years without this level of evidence,” Mitchell S.V. Elkind, MD, said when asked to comment on the study.
Prior secondary analyses of studies, including research into patients with intracranial atherosclerosis, demonstrated benefit from treating to this lower LDL cholesterol target. “These studies were suggestive enough that many of us were treating patients aggressively with statins,” added Dr. Elkind, professor of neurology and epidemiology and chief of the division of neurology clinical outcomes research and population sciences at Columbia University in New York.
“But this really confirms that [fact] with clinical trial evidence,” said Dr. Elkind, “and I think will be very useful to us as clinicians.”
The results could be used to counsel patients about the potential benefits of statin therapy or to motivate primary care providers to treat patients more aggressively, said Dr. Elkind, who will begin his term as president of the American Heart Association/American Stroke Association in July.
This study was supported by a grant from the French Ministry of Health and from SOS-Attaque Cérébrale Association, with unrestricted grants from Pfizer, AstraZeneca, and Merck for French sites and from Pfizer for South Korean sites.
Dr. Amarenco receives research grant support and consulting fees from Pfizer, Merck, and AstraZeneca. Elkind had has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SOURCE: Amarenko P et al. ISC 2020. Late-breaking abstract 9.
LOS ANGELES – In a subanalysis of the TST (Treat Stroke to Target) trial, restricting analysis to only French participants followed for an average of 5 years demonstrated an even more robust potential to reduce recurrent stroke and other major cardiovascular events by treating patients to an LDL target of below 70 mg/dL. Treating LDL to a mean of 66 mg/dL versus 96 mg/dL was associated with a 26% relative risk reduction for the composite endpoint of ischemic stroke, MI, new symptoms requiring urgent coronary or carotid revascularization, and vascular death in an adjusted analysis.
“The results are similar to the main paper but even more spectacular, with no increase in hemorrhagic stroke whatsoever, and positive results on any stroke,” study investigator Pierre Amarenco, MD, professor and chair of the department of neurology and Stroke Centre, Bichat University Hospital, Paris, said.
Dr. Amarenco presented the findings as a late-breaking abstract at the International Stroke Conference sponsored by the American Heart Association. The trial was published simultaneously in the journal Stroke.
In the full TST trial population, risk was reduced by 22% with more-aggressive LDL-lowering treatment, compared with the more lax 90-110 mg/dL target.
The TST cohort included both French and Korean participants. Dr. Amarenco and colleagues focused on the French population in the current study because the group was larger (2,148 vs. 742 Korean participants) and had a longer follow-up, an average of 5.3 years compared to 2.0 years among Korean patients. The initial study had shown “very significant results in the French patients and no apparent effect in Korean patients,” he said. The longer duration of treatment in the French cohort could have contributed to the greater risk reduction, said Dr. Amarenco.
A 2017 European Atherosclerosis Society Consensus Panel statement noted that exposure time to lipid-lowering drugs correlates with outcomes. The European Stroke Organization and the American Heart Association/American Stroke Association guidelines each recommend intensive statin treatment to lower serum lipids following an ischemic stroke of atherosclerotic origin or after a transient ischemic attack (TIA). However, the current researchers noted that the recommendations do not specify specific target numbers.
“Therefore, there is uncertainty about the target levels of LDL cholesterol,” he said.
Aiming at different targets
To learn more, Dr. Amarenco and colleagues randomly assigned 1,073 of the French patients to a target LDL treatment group of 70 mg/dL and another 1,075 to a target range of 90-110 mg/dL. They enrolled participants at 61 sites in France. Mean age was 67 years. All participants had experienced an ischemic stroke within 3 months or a TIA within 15 days of baseline. They presented either with a modified Rankin Scale poststroke score of 0-3 or a TIA that included at least arm and leg motor deficit or speech disturbance that lasted more than 10 minutes.
Investigators could use any type and any dose of statin to reach the respective targets. Statins could be prescribed as monotherapy or in combination with ezetimibe (Zetia) or other agents. The baseline mean LDL cholesterol level was 137 mg/dL in the lower target group and 138 mg/dL in the higher target group, respectively (3.5 mmol/L in both groups). Dr. Amarenco and colleagues measured LDL cholesterol levels at 3 weeks postrandomization and then every 6 months.
A smaller proportion of the lower LDL cholesterol target group experienced the adverse composite outcome, 9.6%, compared with 12.9% of the higher LDL cholesterol target group. This translated to a hazard ratio of 0.73 (95% confidence interval, 0.57-0.94; P = .015). The absolute risk reduction was 3.3% with a number needed to treat of 30.
An analysis adjusted for covariates showed a hazard ratio of 0.74 (95% CI, 0.57-0.95; P = .019).
Cerebral infarction and acute cerebral artery revascularization were reduced by 27% (HR, 0.73; 95% CI, 0.54-0.99; P = .046). Cerebral infarction or intracranial hemorrhage (all strokes) were reduced by 28% (HR, 0.72; 95% CI, 0.54-0.98; P = .023). In this case, there was an absolute risk reduction of 2.9% and a number needed to treat of 34.
In contrast, MI or urgent coronary revascularization following new symptoms were not significantly reduced (HR, 0.66; 95% CI, 0.67-1.20; P = .18). The investigators also reported nonsignificant results regarding vascular death (HR, 0.76; 95% CI, 0.44-1.32; P = .32] and all deaths (HR, 1.0; 95% CI, 0.74-1.35; P = .99).
Dr. Amarenco and colleagues also tracked adverse events. They found intracranial hemorrhage occurred in 13 (1.2%) patients assigned an LDL cholesterol below 70 mg/dL and in 11 (1%) patients assigned an LDL cholesterol of 100 ± 10 mg/dL. In this analysis, the hazard ratio was 1.17 (95% CI, 0.53-2.62; P = .70), and the absolute difference was 0.2%.
The investigators also reported that 10.3% of the lower LDL target group vs 13.6% of the higher LDL target group experienced either the primary outcome or intracranial hemorrhage. This translated to a 25% relative risk reduction (HR, 0.75; 95% CI, 0.58-0.96; P = .021), an absolute risk reduction of 3.3% and a number needed to treat of 30.
Avoiding one in four events
Assessing the French participants in the TST trial showed that targeting LDL below 70 mg/dL for more than 5 years avoided more than one in four subsequent major cardiovascular events among adults who experienced a recent ischemic stroke or TIA.
Furthermore, more intense LDL lowering also avoided more than one in four recurrent cerebral infarctions or urgent carotid revascularizations following a TIA, as well as one in four recurrent cerebral infarctions or hemorrhages (all strokes), compared with the higher LDL target.
“This was obtained without increasing the risk of intracranial hemorrhage with a number needed to treat of 30,” the researchers noted. “In the context of all randomized clinical trials with statin and other lipid-lowering drugs, there is no reason to think that Asian patients do not benefit from statin treatment and from a lower target LDL cholesterol,” the researchers added.
Therefore, they plan to continue assessing the 742 Korean participants until they reach a median of 5 years of follow-up.
Clinically validating results
“My feeling is that these data are highly supportive of a practice that many of us have been using for years without this level of evidence,” Mitchell S.V. Elkind, MD, said when asked to comment on the study.
Prior secondary analyses of studies, including research into patients with intracranial atherosclerosis, demonstrated benefit from treating to this lower LDL cholesterol target. “These studies were suggestive enough that many of us were treating patients aggressively with statins,” added Dr. Elkind, professor of neurology and epidemiology and chief of the division of neurology clinical outcomes research and population sciences at Columbia University in New York.
“But this really confirms that [fact] with clinical trial evidence,” said Dr. Elkind, “and I think will be very useful to us as clinicians.”
The results could be used to counsel patients about the potential benefits of statin therapy or to motivate primary care providers to treat patients more aggressively, said Dr. Elkind, who will begin his term as president of the American Heart Association/American Stroke Association in July.
This study was supported by a grant from the French Ministry of Health and from SOS-Attaque Cérébrale Association, with unrestricted grants from Pfizer, AstraZeneca, and Merck for French sites and from Pfizer for South Korean sites.
Dr. Amarenco receives research grant support and consulting fees from Pfizer, Merck, and AstraZeneca. Elkind had has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SOURCE: Amarenko P et al. ISC 2020. Late-breaking abstract 9.
REPORTING FROM ISC 2020
BASILAR: Endovascular treatment improves outcomes in BAO stroke
LOS ANGELES – Endovascular therapy significantly improved functional outcomes and reduced mortality at 90 days, compared with standard thrombolysis alone, new evidence from a large, prospective registry study suggests.
Participants who received both interventions were almost five times more likely to be able to walk independently at 90 days compared with those who received thrombolysis alone.
Despite multiple trials supporting the potential benefits of endovascular therapy for anterior stroke, little prospective research addresses outcomes associated with an ischemic stroke caused by a posterior basilar artery occlusion (BAO).
“Basilar artery occlusion is the ‘orphan’ of the large vessel occlusions,” Raul Gomes Nogueira, MD, PhD, said here at a late-breaking abstract session at the International Stroke Conference sponsored by the American Heart Association.
“They account for about 5% of the large vessel occlusions – but have the most dismal prognosis.” Severe disability and mortality rates associated with BAO, for example, reach an estimated 68% to 78%, he said.
The results, from the EVT for Acute Basilar Artery Occlusion Study (BASILAR), were also simultaneously published in JAMA Neurology.
Prior studies in this patient population are generally single-center, retrospective studies and “the numbers tend to be small,” said Nogueira, who is affiliated with the Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Emory University School of Medicine in Atlanta, Georgia.
Nogueira and colleagues studied 829 consecutive adults who presented with an acute, symptomatic BAO. They examined a nationwide prospective registry study of people with radiologically confirmed BAO in 47 comprehensive stroke centers across 15 provinces in China.
The median age was 65 years and 74% were men. A total 182 participants received thrombolysis therapy within 6 hours of estimated BAO onset. The 647 people in the dual intervention group also received endovascular therapy within 24 hours.
Standard medical treatment included intravenous rt-PA or urokinase, antiplatelet drugs and systematic anticoagulation alone or in combination. Endovascular therapy included mechanical thrombectomy with stent retrievers and/or thromboaspiration, balloon angioplasty, stenting, intra-arterial thrombolysis, or a combination of these interventions.
Interestingly, participants were not randomly assigned, in part because of the favorable outcomes associated with endovascular therapy. “The high number of patients who received [the dual intervention] may suggest the existence of a lack of equipoise among participating centers,” the researchers note.
Key Efficacy Endpoints
A significantly higher proportion of people in the dual treatment group achieved the primary outcome, functional improvement at 90 days, at 32%, compared with 9.3% in the thrombolysis-only group. This endpoint was defined as a modified Rankin Scale (mRS) score of 3 or less, which reflects an ability to walk independently. The difference was statistically significant (P < .001).
The absolute difference between groups was 22.7% (95% confidence interval, 17.1%-28.2%) with an adjusted odds ratio of 4.70 (95% CI, 2.53-8.75; P < .001) in favor of dual intervention.
The number needed to treat for one additional patient to be able to walk unassisted was 4.4.
Other outcomes, including differences in National Institutes of Health Stroke Scale scores from baseline to 5 to 7 days or discharge, as well as propensity score matching and subgroup analyses, likewise supported the superiority of using both interventions.
Safety Outcomes
Nogueira and colleagues also assessed safety. They found that symptomatic intracerebral hemorrhage (ICH) occurred in 45 patients, or 7.1% of the endovascular treatment group. In contrast, only one patient, or 0.5%, of the standard medical treatment alone cohort experienced an ICH. This difference was statistically significant (P < .001).
Mortality at 90 days was significantly lower in the endovascular therapy plus medical therapy group, 46.2%, compared with 71.4% in the standard medical treatment alone group (P < .001).
The absolute difference in mortality was 25.2% (95% CI, 17.6%-2.8%) favoring dual treatment, with an adjusted odds ratio of 2.93 (95% CI, 1.95-4.40; P < .001).
Rates of other serious adverse events during the 90-day follow-up period were similar in the two study groups, Nogueira said.
He acknowledged that the nonrandomized design was a limitation of the registry study, adding that “sometimes in life it’s important to acknowledge the best of what can be done. It’s very hard when you have access to thrombectomy to randomize people.”
However, other researchers have attempted or are enrolling people with BAO into trials that randomly assign them to endovascular therapy and standard medical treatment or medical treatment alone.
The BEST trial in China, for example, randomly assigned 131 patients to these groups but was stopped early in September 2017. “The BEST trial was terminated prematurely because of loss of equipoise that led to a high crossover rate and drop in valid recruitment,” the current researchers note.
“The other two trials…are facing the challenge of whether they will achieve their inclusion target,” they add, “because a growing number of stroke centers are unwilling to randomize patients to standard medical treatment alone after the many positive results of trials for endovascular treatment in patients with anterior-circulation stroke.”
The BAOCHE trial from China, for example, is ongoing with approximately 110 patients enrolled so far.
Investigators for the Basilar Artery International Cooperation Study (BASICS) in the Netherlands just completed enrollment of their 300th and final patient in December 2019.
“We are hopeful BASICS trial will shed additional light,” Nogueira said. The results are expected to be presented at the European Stroke Organization Conference in Vienna in May 2020.
More Guidance From MRI?
“With the advent of the stent retrievers and successful recanalization, we know there can be better outcomes for patients. And we know the morbidity and mortality of the basilar artery occlusions are so poor that we tend to want to be aggressive in these cases,” session comoderator Shlee S. Song, MD, director of the Comprehensive Stroke Center and associate professor of neurology at Cedars-Sinai Medical Center in Los Angeles, California, told Medscape Medical News when asked to comment on the study.
“I agree that we’ve lost equipoise in this cohort – that we really cannot do a randomized trial anymore. You know if you don’t do anything, 90% of the time there will be a poor outcome,” she added.
This is an important study for showing how BAO patients fare after endovascular treatment, Song said.
One unanswered question from the study is if any of the centers in China used magnetic resonance imaging to help determine the most appropriate candidates for endovascular treatment of these posterior circulation strokes, which is a common practice in the United States, she said.
The study was supported by the National Science Fund for Distinguished Young Scholars, Chongqing Major Disease Prevention and Control Technology Research Project, Army Medical University Clinical Medical Research Talent Training Program, and Major Clinical Innovation Technology Project of the Second Affiliated Hospital of the Army Military Medical University. Sing had no relevant disclosures. Nogueira’s financial disclosures include working as a consultant for Stryker Neurovascular; as a principal investigator on the Imperative trial and the PROST trial; as a steering committee member for Biogen for the CHARM trial; as an advisory board member for Cerenovus/Neuravi, Phenox, Anaconda, Genentech, Biogen, Prolong Pharmaceuticals and Brainomix; and as an advisory board member with stock options for Viz.ai, Corindus Vascular Robotics, Vesalio, Ceretrieve, Astrocyte Pharmaceuticals, and Cerebrotech.
This article first appeared on Medscape.com.
SOURCE: Nogueira RG et al. ISC 2020. Late-breaking abstract 17.
LOS ANGELES – Endovascular therapy significantly improved functional outcomes and reduced mortality at 90 days, compared with standard thrombolysis alone, new evidence from a large, prospective registry study suggests.
Participants who received both interventions were almost five times more likely to be able to walk independently at 90 days compared with those who received thrombolysis alone.
Despite multiple trials supporting the potential benefits of endovascular therapy for anterior stroke, little prospective research addresses outcomes associated with an ischemic stroke caused by a posterior basilar artery occlusion (BAO).
“Basilar artery occlusion is the ‘orphan’ of the large vessel occlusions,” Raul Gomes Nogueira, MD, PhD, said here at a late-breaking abstract session at the International Stroke Conference sponsored by the American Heart Association.
“They account for about 5% of the large vessel occlusions – but have the most dismal prognosis.” Severe disability and mortality rates associated with BAO, for example, reach an estimated 68% to 78%, he said.
The results, from the EVT for Acute Basilar Artery Occlusion Study (BASILAR), were also simultaneously published in JAMA Neurology.
Prior studies in this patient population are generally single-center, retrospective studies and “the numbers tend to be small,” said Nogueira, who is affiliated with the Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Emory University School of Medicine in Atlanta, Georgia.
Nogueira and colleagues studied 829 consecutive adults who presented with an acute, symptomatic BAO. They examined a nationwide prospective registry study of people with radiologically confirmed BAO in 47 comprehensive stroke centers across 15 provinces in China.
The median age was 65 years and 74% were men. A total 182 participants received thrombolysis therapy within 6 hours of estimated BAO onset. The 647 people in the dual intervention group also received endovascular therapy within 24 hours.
Standard medical treatment included intravenous rt-PA or urokinase, antiplatelet drugs and systematic anticoagulation alone or in combination. Endovascular therapy included mechanical thrombectomy with stent retrievers and/or thromboaspiration, balloon angioplasty, stenting, intra-arterial thrombolysis, or a combination of these interventions.
Interestingly, participants were not randomly assigned, in part because of the favorable outcomes associated with endovascular therapy. “The high number of patients who received [the dual intervention] may suggest the existence of a lack of equipoise among participating centers,” the researchers note.
Key Efficacy Endpoints
A significantly higher proportion of people in the dual treatment group achieved the primary outcome, functional improvement at 90 days, at 32%, compared with 9.3% in the thrombolysis-only group. This endpoint was defined as a modified Rankin Scale (mRS) score of 3 or less, which reflects an ability to walk independently. The difference was statistically significant (P < .001).
The absolute difference between groups was 22.7% (95% confidence interval, 17.1%-28.2%) with an adjusted odds ratio of 4.70 (95% CI, 2.53-8.75; P < .001) in favor of dual intervention.
The number needed to treat for one additional patient to be able to walk unassisted was 4.4.
Other outcomes, including differences in National Institutes of Health Stroke Scale scores from baseline to 5 to 7 days or discharge, as well as propensity score matching and subgroup analyses, likewise supported the superiority of using both interventions.
Safety Outcomes
Nogueira and colleagues also assessed safety. They found that symptomatic intracerebral hemorrhage (ICH) occurred in 45 patients, or 7.1% of the endovascular treatment group. In contrast, only one patient, or 0.5%, of the standard medical treatment alone cohort experienced an ICH. This difference was statistically significant (P < .001).
Mortality at 90 days was significantly lower in the endovascular therapy plus medical therapy group, 46.2%, compared with 71.4% in the standard medical treatment alone group (P < .001).
The absolute difference in mortality was 25.2% (95% CI, 17.6%-2.8%) favoring dual treatment, with an adjusted odds ratio of 2.93 (95% CI, 1.95-4.40; P < .001).
Rates of other serious adverse events during the 90-day follow-up period were similar in the two study groups, Nogueira said.
He acknowledged that the nonrandomized design was a limitation of the registry study, adding that “sometimes in life it’s important to acknowledge the best of what can be done. It’s very hard when you have access to thrombectomy to randomize people.”
However, other researchers have attempted or are enrolling people with BAO into trials that randomly assign them to endovascular therapy and standard medical treatment or medical treatment alone.
The BEST trial in China, for example, randomly assigned 131 patients to these groups but was stopped early in September 2017. “The BEST trial was terminated prematurely because of loss of equipoise that led to a high crossover rate and drop in valid recruitment,” the current researchers note.
“The other two trials…are facing the challenge of whether they will achieve their inclusion target,” they add, “because a growing number of stroke centers are unwilling to randomize patients to standard medical treatment alone after the many positive results of trials for endovascular treatment in patients with anterior-circulation stroke.”
The BAOCHE trial from China, for example, is ongoing with approximately 110 patients enrolled so far.
Investigators for the Basilar Artery International Cooperation Study (BASICS) in the Netherlands just completed enrollment of their 300th and final patient in December 2019.
“We are hopeful BASICS trial will shed additional light,” Nogueira said. The results are expected to be presented at the European Stroke Organization Conference in Vienna in May 2020.
More Guidance From MRI?
“With the advent of the stent retrievers and successful recanalization, we know there can be better outcomes for patients. And we know the morbidity and mortality of the basilar artery occlusions are so poor that we tend to want to be aggressive in these cases,” session comoderator Shlee S. Song, MD, director of the Comprehensive Stroke Center and associate professor of neurology at Cedars-Sinai Medical Center in Los Angeles, California, told Medscape Medical News when asked to comment on the study.
“I agree that we’ve lost equipoise in this cohort – that we really cannot do a randomized trial anymore. You know if you don’t do anything, 90% of the time there will be a poor outcome,” she added.
This is an important study for showing how BAO patients fare after endovascular treatment, Song said.
One unanswered question from the study is if any of the centers in China used magnetic resonance imaging to help determine the most appropriate candidates for endovascular treatment of these posterior circulation strokes, which is a common practice in the United States, she said.
The study was supported by the National Science Fund for Distinguished Young Scholars, Chongqing Major Disease Prevention and Control Technology Research Project, Army Medical University Clinical Medical Research Talent Training Program, and Major Clinical Innovation Technology Project of the Second Affiliated Hospital of the Army Military Medical University. Sing had no relevant disclosures. Nogueira’s financial disclosures include working as a consultant for Stryker Neurovascular; as a principal investigator on the Imperative trial and the PROST trial; as a steering committee member for Biogen for the CHARM trial; as an advisory board member for Cerenovus/Neuravi, Phenox, Anaconda, Genentech, Biogen, Prolong Pharmaceuticals and Brainomix; and as an advisory board member with stock options for Viz.ai, Corindus Vascular Robotics, Vesalio, Ceretrieve, Astrocyte Pharmaceuticals, and Cerebrotech.
This article first appeared on Medscape.com.
SOURCE: Nogueira RG et al. ISC 2020. Late-breaking abstract 17.
LOS ANGELES – Endovascular therapy significantly improved functional outcomes and reduced mortality at 90 days, compared with standard thrombolysis alone, new evidence from a large, prospective registry study suggests.
Participants who received both interventions were almost five times more likely to be able to walk independently at 90 days compared with those who received thrombolysis alone.
Despite multiple trials supporting the potential benefits of endovascular therapy for anterior stroke, little prospective research addresses outcomes associated with an ischemic stroke caused by a posterior basilar artery occlusion (BAO).
“Basilar artery occlusion is the ‘orphan’ of the large vessel occlusions,” Raul Gomes Nogueira, MD, PhD, said here at a late-breaking abstract session at the International Stroke Conference sponsored by the American Heart Association.
“They account for about 5% of the large vessel occlusions – but have the most dismal prognosis.” Severe disability and mortality rates associated with BAO, for example, reach an estimated 68% to 78%, he said.
The results, from the EVT for Acute Basilar Artery Occlusion Study (BASILAR), were also simultaneously published in JAMA Neurology.
Prior studies in this patient population are generally single-center, retrospective studies and “the numbers tend to be small,” said Nogueira, who is affiliated with the Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Emory University School of Medicine in Atlanta, Georgia.
Nogueira and colleagues studied 829 consecutive adults who presented with an acute, symptomatic BAO. They examined a nationwide prospective registry study of people with radiologically confirmed BAO in 47 comprehensive stroke centers across 15 provinces in China.
The median age was 65 years and 74% were men. A total 182 participants received thrombolysis therapy within 6 hours of estimated BAO onset. The 647 people in the dual intervention group also received endovascular therapy within 24 hours.
Standard medical treatment included intravenous rt-PA or urokinase, antiplatelet drugs and systematic anticoagulation alone or in combination. Endovascular therapy included mechanical thrombectomy with stent retrievers and/or thromboaspiration, balloon angioplasty, stenting, intra-arterial thrombolysis, or a combination of these interventions.
Interestingly, participants were not randomly assigned, in part because of the favorable outcomes associated with endovascular therapy. “The high number of patients who received [the dual intervention] may suggest the existence of a lack of equipoise among participating centers,” the researchers note.
Key Efficacy Endpoints
A significantly higher proportion of people in the dual treatment group achieved the primary outcome, functional improvement at 90 days, at 32%, compared with 9.3% in the thrombolysis-only group. This endpoint was defined as a modified Rankin Scale (mRS) score of 3 or less, which reflects an ability to walk independently. The difference was statistically significant (P < .001).
The absolute difference between groups was 22.7% (95% confidence interval, 17.1%-28.2%) with an adjusted odds ratio of 4.70 (95% CI, 2.53-8.75; P < .001) in favor of dual intervention.
The number needed to treat for one additional patient to be able to walk unassisted was 4.4.
Other outcomes, including differences in National Institutes of Health Stroke Scale scores from baseline to 5 to 7 days or discharge, as well as propensity score matching and subgroup analyses, likewise supported the superiority of using both interventions.
Safety Outcomes
Nogueira and colleagues also assessed safety. They found that symptomatic intracerebral hemorrhage (ICH) occurred in 45 patients, or 7.1% of the endovascular treatment group. In contrast, only one patient, or 0.5%, of the standard medical treatment alone cohort experienced an ICH. This difference was statistically significant (P < .001).
Mortality at 90 days was significantly lower in the endovascular therapy plus medical therapy group, 46.2%, compared with 71.4% in the standard medical treatment alone group (P < .001).
The absolute difference in mortality was 25.2% (95% CI, 17.6%-2.8%) favoring dual treatment, with an adjusted odds ratio of 2.93 (95% CI, 1.95-4.40; P < .001).
Rates of other serious adverse events during the 90-day follow-up period were similar in the two study groups, Nogueira said.
He acknowledged that the nonrandomized design was a limitation of the registry study, adding that “sometimes in life it’s important to acknowledge the best of what can be done. It’s very hard when you have access to thrombectomy to randomize people.”
However, other researchers have attempted or are enrolling people with BAO into trials that randomly assign them to endovascular therapy and standard medical treatment or medical treatment alone.
The BEST trial in China, for example, randomly assigned 131 patients to these groups but was stopped early in September 2017. “The BEST trial was terminated prematurely because of loss of equipoise that led to a high crossover rate and drop in valid recruitment,” the current researchers note.
“The other two trials…are facing the challenge of whether they will achieve their inclusion target,” they add, “because a growing number of stroke centers are unwilling to randomize patients to standard medical treatment alone after the many positive results of trials for endovascular treatment in patients with anterior-circulation stroke.”
The BAOCHE trial from China, for example, is ongoing with approximately 110 patients enrolled so far.
Investigators for the Basilar Artery International Cooperation Study (BASICS) in the Netherlands just completed enrollment of their 300th and final patient in December 2019.
“We are hopeful BASICS trial will shed additional light,” Nogueira said. The results are expected to be presented at the European Stroke Organization Conference in Vienna in May 2020.
More Guidance From MRI?
“With the advent of the stent retrievers and successful recanalization, we know there can be better outcomes for patients. And we know the morbidity and mortality of the basilar artery occlusions are so poor that we tend to want to be aggressive in these cases,” session comoderator Shlee S. Song, MD, director of the Comprehensive Stroke Center and associate professor of neurology at Cedars-Sinai Medical Center in Los Angeles, California, told Medscape Medical News when asked to comment on the study.
“I agree that we’ve lost equipoise in this cohort – that we really cannot do a randomized trial anymore. You know if you don’t do anything, 90% of the time there will be a poor outcome,” she added.
This is an important study for showing how BAO patients fare after endovascular treatment, Song said.
One unanswered question from the study is if any of the centers in China used magnetic resonance imaging to help determine the most appropriate candidates for endovascular treatment of these posterior circulation strokes, which is a common practice in the United States, she said.
The study was supported by the National Science Fund for Distinguished Young Scholars, Chongqing Major Disease Prevention and Control Technology Research Project, Army Medical University Clinical Medical Research Talent Training Program, and Major Clinical Innovation Technology Project of the Second Affiliated Hospital of the Army Military Medical University. Sing had no relevant disclosures. Nogueira’s financial disclosures include working as a consultant for Stryker Neurovascular; as a principal investigator on the Imperative trial and the PROST trial; as a steering committee member for Biogen for the CHARM trial; as an advisory board member for Cerenovus/Neuravi, Phenox, Anaconda, Genentech, Biogen, Prolong Pharmaceuticals and Brainomix; and as an advisory board member with stock options for Viz.ai, Corindus Vascular Robotics, Vesalio, Ceretrieve, Astrocyte Pharmaceuticals, and Cerebrotech.
This article first appeared on Medscape.com.
SOURCE: Nogueira RG et al. ISC 2020. Late-breaking abstract 17.
REPORTING FROM ISC 2020