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Stroke thrombolysis looks safe 31+ days after prior stroke
HONOLULU – , based on a review of more than 40,000 U.S. stroke patients.
Current U.S. stroke management guidelines say that thrombolytic therapy with tissue plasminogen activator (tPA; alteplase; Activase) is contraindicated for index stroke patients who had a prior stroke within the previous 3 months (Stroke. 2018 Mar;49[3]:e46-99). But analysis of 293 U.S. patients who received thrombolytic treatment for an index acute ischemic stroke despite having had a recent, prior stroke showed no increased risk for adverse outcomes when the prior stroke occurred more than 30 days before, Shreyansh Shah, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The risk of symptomatic intracranial hemorrhage [ICH] after thrombolysis was highest among those with a history of prior ischemic stroke within the past 14 days,” said Dr. Shah, a neurologist at Duke University in Durham, N.C.
“Even after many adjustments we still saw a high risk of symptomatic ICH within the first 2 weeks, suggesting that these patients are at especially high risk” from treatment with tissue plasminogen activator for the index stroke. These findings “are very important because I don’t see a randomized trial happening to test the hypothesis,” Dr. Shah said in an interview.
He also suggested that prior treatment with tPA was not an important factor, just the occurrence of a recent, prior ischemic stoke that left blood vessels in the affected brain region “friable and at high risk for hemorrhage,” he said.
His study used data from 40,396 patients with an acute ischemic stroke who presented at and received treatment with tPA at any of 1,522 hospitals that participated in the Get With the Guidelines-Stroke program during 2009-2015. The analysis focused on 30,655 of these patients with no prior stroke history who served as the controls, and 293 who had a prior ischemic stroke within the preceding 90 days. These 293 patients further broke into 43 who received thrombolysis within 14 days of their prior stroke, 47 who had the treatment 15-30 days after their prior stroke, and 203 who underwent thrombolysis 31-90 days after their prior stroke. Patients ages’ in both the no-stroke history and recent-stroke subgroups each averaged 80 years.
A comparison between all 293 patients who had a prior stroke within 90 days and the controls showed no statistically significant difference in the rate of symptomatic ICH: 5% among those with no stroke history and 8% in those with a recent stroke. There was also no significant difference in the rate of in-hospital mortality, occurring in 9% of those without a prior stroke, compared with 13% of those with a recent prior stroke. But the patients with no stroke history fared better by other measures, with a significantly lower rate of in-hospital death or discharge to a hospice, and also a significantly higher rate of 0-1 scores on the modified Rankin Scale, compared with patients with a history of prior stroke.
A more granular analysis of the timing of the prior stroke showed that most of risk from thrombolysis clustered in patients with a very recent prior stroke. The 43 patients with a prior stroke within the preceding 14 days had a symptomatic ICH rate of 16% after thrombolysis, 3.7-fold higher than the control patients in an adjusted analysis. Once the patients with a prior stroke within the past 14 days were pulled out, the remaining patients with prior strokes 15-30 days before as well as those with a prior stroke 31-90 days previously had symptomatic ICH rates that were not significantly different from the controls, Dr. Shah reported.
The results also showed an increased rate of in-hospital mortality or discharge to a hospice clustered in patients treated either within 14 days or during 15-30 days after a prior stroke. In both subgroups, the rate of this outcome was about triple the control rate. In the subgroup treated with thrombolysis 31-90 days after a prior stroke, the rate of in-hospital mortality or discharge to a hospice was about the same as the controls.
“It appears that some patients could benefit from tPA; there is a potential safety signal. It allows for some discretion when using thrombolytic treatment” in patients with a recent, prior stroke, Dr. Shah suggested. “This is by far the largest analysis ever reported” for thrombolytic treatment of patients following a recent, prior stroke, noted Ying Xian, MD, PhD, a Duke neurologist and study coauthor.
But Gregg C. Fonarow, MD, another coauthor, cautioned against immediately applying this finding to practice. “The findings of Dr. Shah’s study suggest that selected patients with prior stroke within a 14- to 90-day window may be considered for tPA treatment. However, further study is warranted given the relatively small number of patients,” said Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Shah and Dr. Xian had no disclosures. Dr. Fonarow had no relevant disclosures.
SOURCE: Shah S et al. Stroke. 2019 Feb;50(Suppl_1): Abstract 35.
HONOLULU – , based on a review of more than 40,000 U.S. stroke patients.
Current U.S. stroke management guidelines say that thrombolytic therapy with tissue plasminogen activator (tPA; alteplase; Activase) is contraindicated for index stroke patients who had a prior stroke within the previous 3 months (Stroke. 2018 Mar;49[3]:e46-99). But analysis of 293 U.S. patients who received thrombolytic treatment for an index acute ischemic stroke despite having had a recent, prior stroke showed no increased risk for adverse outcomes when the prior stroke occurred more than 30 days before, Shreyansh Shah, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The risk of symptomatic intracranial hemorrhage [ICH] after thrombolysis was highest among those with a history of prior ischemic stroke within the past 14 days,” said Dr. Shah, a neurologist at Duke University in Durham, N.C.
“Even after many adjustments we still saw a high risk of symptomatic ICH within the first 2 weeks, suggesting that these patients are at especially high risk” from treatment with tissue plasminogen activator for the index stroke. These findings “are very important because I don’t see a randomized trial happening to test the hypothesis,” Dr. Shah said in an interview.
He also suggested that prior treatment with tPA was not an important factor, just the occurrence of a recent, prior ischemic stoke that left blood vessels in the affected brain region “friable and at high risk for hemorrhage,” he said.
His study used data from 40,396 patients with an acute ischemic stroke who presented at and received treatment with tPA at any of 1,522 hospitals that participated in the Get With the Guidelines-Stroke program during 2009-2015. The analysis focused on 30,655 of these patients with no prior stroke history who served as the controls, and 293 who had a prior ischemic stroke within the preceding 90 days. These 293 patients further broke into 43 who received thrombolysis within 14 days of their prior stroke, 47 who had the treatment 15-30 days after their prior stroke, and 203 who underwent thrombolysis 31-90 days after their prior stroke. Patients ages’ in both the no-stroke history and recent-stroke subgroups each averaged 80 years.
A comparison between all 293 patients who had a prior stroke within 90 days and the controls showed no statistically significant difference in the rate of symptomatic ICH: 5% among those with no stroke history and 8% in those with a recent stroke. There was also no significant difference in the rate of in-hospital mortality, occurring in 9% of those without a prior stroke, compared with 13% of those with a recent prior stroke. But the patients with no stroke history fared better by other measures, with a significantly lower rate of in-hospital death or discharge to a hospice, and also a significantly higher rate of 0-1 scores on the modified Rankin Scale, compared with patients with a history of prior stroke.
A more granular analysis of the timing of the prior stroke showed that most of risk from thrombolysis clustered in patients with a very recent prior stroke. The 43 patients with a prior stroke within the preceding 14 days had a symptomatic ICH rate of 16% after thrombolysis, 3.7-fold higher than the control patients in an adjusted analysis. Once the patients with a prior stroke within the past 14 days were pulled out, the remaining patients with prior strokes 15-30 days before as well as those with a prior stroke 31-90 days previously had symptomatic ICH rates that were not significantly different from the controls, Dr. Shah reported.
The results also showed an increased rate of in-hospital mortality or discharge to a hospice clustered in patients treated either within 14 days or during 15-30 days after a prior stroke. In both subgroups, the rate of this outcome was about triple the control rate. In the subgroup treated with thrombolysis 31-90 days after a prior stroke, the rate of in-hospital mortality or discharge to a hospice was about the same as the controls.
“It appears that some patients could benefit from tPA; there is a potential safety signal. It allows for some discretion when using thrombolytic treatment” in patients with a recent, prior stroke, Dr. Shah suggested. “This is by far the largest analysis ever reported” for thrombolytic treatment of patients following a recent, prior stroke, noted Ying Xian, MD, PhD, a Duke neurologist and study coauthor.
But Gregg C. Fonarow, MD, another coauthor, cautioned against immediately applying this finding to practice. “The findings of Dr. Shah’s study suggest that selected patients with prior stroke within a 14- to 90-day window may be considered for tPA treatment. However, further study is warranted given the relatively small number of patients,” said Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Shah and Dr. Xian had no disclosures. Dr. Fonarow had no relevant disclosures.
SOURCE: Shah S et al. Stroke. 2019 Feb;50(Suppl_1): Abstract 35.
HONOLULU – , based on a review of more than 40,000 U.S. stroke patients.
Current U.S. stroke management guidelines say that thrombolytic therapy with tissue plasminogen activator (tPA; alteplase; Activase) is contraindicated for index stroke patients who had a prior stroke within the previous 3 months (Stroke. 2018 Mar;49[3]:e46-99). But analysis of 293 U.S. patients who received thrombolytic treatment for an index acute ischemic stroke despite having had a recent, prior stroke showed no increased risk for adverse outcomes when the prior stroke occurred more than 30 days before, Shreyansh Shah, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“The risk of symptomatic intracranial hemorrhage [ICH] after thrombolysis was highest among those with a history of prior ischemic stroke within the past 14 days,” said Dr. Shah, a neurologist at Duke University in Durham, N.C.
“Even after many adjustments we still saw a high risk of symptomatic ICH within the first 2 weeks, suggesting that these patients are at especially high risk” from treatment with tissue plasminogen activator for the index stroke. These findings “are very important because I don’t see a randomized trial happening to test the hypothesis,” Dr. Shah said in an interview.
He also suggested that prior treatment with tPA was not an important factor, just the occurrence of a recent, prior ischemic stoke that left blood vessels in the affected brain region “friable and at high risk for hemorrhage,” he said.
His study used data from 40,396 patients with an acute ischemic stroke who presented at and received treatment with tPA at any of 1,522 hospitals that participated in the Get With the Guidelines-Stroke program during 2009-2015. The analysis focused on 30,655 of these patients with no prior stroke history who served as the controls, and 293 who had a prior ischemic stroke within the preceding 90 days. These 293 patients further broke into 43 who received thrombolysis within 14 days of their prior stroke, 47 who had the treatment 15-30 days after their prior stroke, and 203 who underwent thrombolysis 31-90 days after their prior stroke. Patients ages’ in both the no-stroke history and recent-stroke subgroups each averaged 80 years.
A comparison between all 293 patients who had a prior stroke within 90 days and the controls showed no statistically significant difference in the rate of symptomatic ICH: 5% among those with no stroke history and 8% in those with a recent stroke. There was also no significant difference in the rate of in-hospital mortality, occurring in 9% of those without a prior stroke, compared with 13% of those with a recent prior stroke. But the patients with no stroke history fared better by other measures, with a significantly lower rate of in-hospital death or discharge to a hospice, and also a significantly higher rate of 0-1 scores on the modified Rankin Scale, compared with patients with a history of prior stroke.
A more granular analysis of the timing of the prior stroke showed that most of risk from thrombolysis clustered in patients with a very recent prior stroke. The 43 patients with a prior stroke within the preceding 14 days had a symptomatic ICH rate of 16% after thrombolysis, 3.7-fold higher than the control patients in an adjusted analysis. Once the patients with a prior stroke within the past 14 days were pulled out, the remaining patients with prior strokes 15-30 days before as well as those with a prior stroke 31-90 days previously had symptomatic ICH rates that were not significantly different from the controls, Dr. Shah reported.
The results also showed an increased rate of in-hospital mortality or discharge to a hospice clustered in patients treated either within 14 days or during 15-30 days after a prior stroke. In both subgroups, the rate of this outcome was about triple the control rate. In the subgroup treated with thrombolysis 31-90 days after a prior stroke, the rate of in-hospital mortality or discharge to a hospice was about the same as the controls.
“It appears that some patients could benefit from tPA; there is a potential safety signal. It allows for some discretion when using thrombolytic treatment” in patients with a recent, prior stroke, Dr. Shah suggested. “This is by far the largest analysis ever reported” for thrombolytic treatment of patients following a recent, prior stroke, noted Ying Xian, MD, PhD, a Duke neurologist and study coauthor.
But Gregg C. Fonarow, MD, another coauthor, cautioned against immediately applying this finding to practice. “The findings of Dr. Shah’s study suggest that selected patients with prior stroke within a 14- to 90-day window may be considered for tPA treatment. However, further study is warranted given the relatively small number of patients,” said Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Shah and Dr. Xian had no disclosures. Dr. Fonarow had no relevant disclosures.
SOURCE: Shah S et al. Stroke. 2019 Feb;50(Suppl_1): Abstract 35.
REPORTING FROM ISC 2019
Stroke endovascular therapy: The more you do, the better you do
HONOLULU – The well-documented link between higher procedure volumes and better procedure efficacy also applies to endovascular thrombectomy for acute ischemic stroke.
in analysis of data from two different U.S. sources: the National Inpatient Sample (NIS) and the state of Florida, Sunil A. Sheth, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The finding raises questions about how to best triage patients with an acute ischemic stroke, suggesting that, in at least some situations, patients might be better served being taken to a higher-volume center even if it’s not the closest, noted Dr. Sheth, The results also suggest that the findings in the trials proving the value of EST run primarily at large, tertiary care, referral centers might not be generalizable to all centers that start an endovascular program.
The study looked at data collected during 2006-2016 in Florida and during 2012-2016 in the NIS, and found that in both databases the rate of EST procedures performed showed steadily increasing use over time, with a sharp increase in the number of centers performing EST in 2015. Each of the two data sets also showed that better discharge outcomes occurred in patients treated at centers with the highest procedural volumes.
In the nationwide NIS data, for every 10 additional patients a center treated with EST annually, the incidence of a “good” hospital-discharge outcome (defined as either discharge home or to an acute rehabilitation hospital) rose by 30%, compared with lower-volume centers in a multivariate regression analysis, a statistically significant relationship, said Dr. Sheth, a neurologist at the University of Texas, Houston. This volume-outcome relationship held fairly constant through volumes up to about 50 EST cases annually. “The more the better,” he observed.
“The data suggest that EST outcomes are not always the same,” but right now most emergency medical service systems do not take EST case volume into account when deciding where to take an acute stroke patient, Dr. Sheth said in an interview. But he cautioned against an oversimplified focus on just EST case volume.
A link between volume and better outcomes “is easy to understand and not surprising. We see this relationship for a variety of procedures. The data suggest we need to consider procedure volumes. But volume is only part of makes for good outcomes; it’s not the only factor,” he stressed.
Dr. Sheth and his associates used data collected by the Florida Agency for Health Care Administration on 3,890 acute ischemic stroke patients treated with EST at 56 Florida hospitals and on 42,505 such patients in the NIS database treated at 2,260 U.S. hospitals. During the 11-year period for Florida data collection, the number of centers performing EST in the state rose steadily at an average rate of about four new centers per year. Although the number of EST procedures done also rose sharply, in general over time a higher percentage of patients underwent treatment at lower-volume centers. Similar patterns existed in the national data. The Florida data showed a statistically significant 10% improvement in good discharge outcomes for every 10 additional EST patients a center treated a year, consistent with the NIS data.
Concurrently with Dr. Sheth’s report, the results also appeared in an article published online (Stroke. 2019 Feb 6. doi: 10.1161/STROKEAHA.118.023967).
Dr. Sheth reported no disclosures.
SOURCE: Sheth SA et al. ISC 2019, Abstract 002.
The idea that when centers perform more of a procedure, such as endovascular thrombectomy for acute ischemic stroke, they more often do it better is intuitively plausible, which helps makes these findings believable. It’s also a relationship we’ve already seen for other types of endovascular therapies. What this study did not address were other factors beyond case volume also might also make important contributions to outcome, such as the speed of treatment delivery.
Volume thresholds for endovascular stroke programs will come eventually, but for the time being our focus should be on insuring wide access to endovascular treatment.
Bruce Ovbiagele, MD, a neurologist and chief of staff for the San Francisco Veteran Affairs Health Care System, made these comments in an interview. He reported no disclosures.
The idea that when centers perform more of a procedure, such as endovascular thrombectomy for acute ischemic stroke, they more often do it better is intuitively plausible, which helps makes these findings believable. It’s also a relationship we’ve already seen for other types of endovascular therapies. What this study did not address were other factors beyond case volume also might also make important contributions to outcome, such as the speed of treatment delivery.
Volume thresholds for endovascular stroke programs will come eventually, but for the time being our focus should be on insuring wide access to endovascular treatment.
Bruce Ovbiagele, MD, a neurologist and chief of staff for the San Francisco Veteran Affairs Health Care System, made these comments in an interview. He reported no disclosures.
The idea that when centers perform more of a procedure, such as endovascular thrombectomy for acute ischemic stroke, they more often do it better is intuitively plausible, which helps makes these findings believable. It’s also a relationship we’ve already seen for other types of endovascular therapies. What this study did not address were other factors beyond case volume also might also make important contributions to outcome, such as the speed of treatment delivery.
Volume thresholds for endovascular stroke programs will come eventually, but for the time being our focus should be on insuring wide access to endovascular treatment.
Bruce Ovbiagele, MD, a neurologist and chief of staff for the San Francisco Veteran Affairs Health Care System, made these comments in an interview. He reported no disclosures.
HONOLULU – The well-documented link between higher procedure volumes and better procedure efficacy also applies to endovascular thrombectomy for acute ischemic stroke.
in analysis of data from two different U.S. sources: the National Inpatient Sample (NIS) and the state of Florida, Sunil A. Sheth, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The finding raises questions about how to best triage patients with an acute ischemic stroke, suggesting that, in at least some situations, patients might be better served being taken to a higher-volume center even if it’s not the closest, noted Dr. Sheth, The results also suggest that the findings in the trials proving the value of EST run primarily at large, tertiary care, referral centers might not be generalizable to all centers that start an endovascular program.
The study looked at data collected during 2006-2016 in Florida and during 2012-2016 in the NIS, and found that in both databases the rate of EST procedures performed showed steadily increasing use over time, with a sharp increase in the number of centers performing EST in 2015. Each of the two data sets also showed that better discharge outcomes occurred in patients treated at centers with the highest procedural volumes.
In the nationwide NIS data, for every 10 additional patients a center treated with EST annually, the incidence of a “good” hospital-discharge outcome (defined as either discharge home or to an acute rehabilitation hospital) rose by 30%, compared with lower-volume centers in a multivariate regression analysis, a statistically significant relationship, said Dr. Sheth, a neurologist at the University of Texas, Houston. This volume-outcome relationship held fairly constant through volumes up to about 50 EST cases annually. “The more the better,” he observed.
“The data suggest that EST outcomes are not always the same,” but right now most emergency medical service systems do not take EST case volume into account when deciding where to take an acute stroke patient, Dr. Sheth said in an interview. But he cautioned against an oversimplified focus on just EST case volume.
A link between volume and better outcomes “is easy to understand and not surprising. We see this relationship for a variety of procedures. The data suggest we need to consider procedure volumes. But volume is only part of makes for good outcomes; it’s not the only factor,” he stressed.
Dr. Sheth and his associates used data collected by the Florida Agency for Health Care Administration on 3,890 acute ischemic stroke patients treated with EST at 56 Florida hospitals and on 42,505 such patients in the NIS database treated at 2,260 U.S. hospitals. During the 11-year period for Florida data collection, the number of centers performing EST in the state rose steadily at an average rate of about four new centers per year. Although the number of EST procedures done also rose sharply, in general over time a higher percentage of patients underwent treatment at lower-volume centers. Similar patterns existed in the national data. The Florida data showed a statistically significant 10% improvement in good discharge outcomes for every 10 additional EST patients a center treated a year, consistent with the NIS data.
Concurrently with Dr. Sheth’s report, the results also appeared in an article published online (Stroke. 2019 Feb 6. doi: 10.1161/STROKEAHA.118.023967).
Dr. Sheth reported no disclosures.
SOURCE: Sheth SA et al. ISC 2019, Abstract 002.
HONOLULU – The well-documented link between higher procedure volumes and better procedure efficacy also applies to endovascular thrombectomy for acute ischemic stroke.
in analysis of data from two different U.S. sources: the National Inpatient Sample (NIS) and the state of Florida, Sunil A. Sheth, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The finding raises questions about how to best triage patients with an acute ischemic stroke, suggesting that, in at least some situations, patients might be better served being taken to a higher-volume center even if it’s not the closest, noted Dr. Sheth, The results also suggest that the findings in the trials proving the value of EST run primarily at large, tertiary care, referral centers might not be generalizable to all centers that start an endovascular program.
The study looked at data collected during 2006-2016 in Florida and during 2012-2016 in the NIS, and found that in both databases the rate of EST procedures performed showed steadily increasing use over time, with a sharp increase in the number of centers performing EST in 2015. Each of the two data sets also showed that better discharge outcomes occurred in patients treated at centers with the highest procedural volumes.
In the nationwide NIS data, for every 10 additional patients a center treated with EST annually, the incidence of a “good” hospital-discharge outcome (defined as either discharge home or to an acute rehabilitation hospital) rose by 30%, compared with lower-volume centers in a multivariate regression analysis, a statistically significant relationship, said Dr. Sheth, a neurologist at the University of Texas, Houston. This volume-outcome relationship held fairly constant through volumes up to about 50 EST cases annually. “The more the better,” he observed.
“The data suggest that EST outcomes are not always the same,” but right now most emergency medical service systems do not take EST case volume into account when deciding where to take an acute stroke patient, Dr. Sheth said in an interview. But he cautioned against an oversimplified focus on just EST case volume.
A link between volume and better outcomes “is easy to understand and not surprising. We see this relationship for a variety of procedures. The data suggest we need to consider procedure volumes. But volume is only part of makes for good outcomes; it’s not the only factor,” he stressed.
Dr. Sheth and his associates used data collected by the Florida Agency for Health Care Administration on 3,890 acute ischemic stroke patients treated with EST at 56 Florida hospitals and on 42,505 such patients in the NIS database treated at 2,260 U.S. hospitals. During the 11-year period for Florida data collection, the number of centers performing EST in the state rose steadily at an average rate of about four new centers per year. Although the number of EST procedures done also rose sharply, in general over time a higher percentage of patients underwent treatment at lower-volume centers. Similar patterns existed in the national data. The Florida data showed a statistically significant 10% improvement in good discharge outcomes for every 10 additional EST patients a center treated a year, consistent with the NIS data.
Concurrently with Dr. Sheth’s report, the results also appeared in an article published online (Stroke. 2019 Feb 6. doi: 10.1161/STROKEAHA.118.023967).
Dr. Sheth reported no disclosures.
SOURCE: Sheth SA et al. ISC 2019, Abstract 002.
REPORTING FROM ISC 2019
Noncardiac surgery has 7% covert stroke rate in elderly
HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.
By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.
Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).
Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.
The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.
The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.
SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.
HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.
By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.
Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).
Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.
The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.
The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.
SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.
HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.
By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.
Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).
Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.
The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.
The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.
SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.
REPORTING FROM ISC 2019
Key clinical point:
Major finding: Elderly patients who underwent noncardiac surgery had a 7% incidence of covert stroke.
Study details: NeuroVISION, a prospective, multicenter, observational study with 1,114 patients.
Disclosures: NeuroVISION did not receive commercial funding. Dr. Mrkobrada had no disclosures.
Source: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.
Minimally invasive ICH lysis safely helps when clot adequately shrinks
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
REPORTING FROM ISC 2019
Key clinical point: Minimally-invasive intracerebral clot lysis was safe and often effective when the residual clot shrank to 15 mL or less.
Major finding: One year after entry, 45% of MISTIE-treated patients and 41% of controls had a modified Rankin Scale score of 0-3.
Study details: MISTIE III, a multicenter, international, randomized trial of 499 patients.
Disclosures: MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
Source: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
Deferoxamine does not improve 90-day outcomes after ICH
HONOLULU – (ICH), according to trial results described at the International Stroke Conference sponsored by the American Heart Association. However, the drug is safe and well tolerated and data suggest that it may improve outcomes at 180 days.
Animal studies indicate that iron, which is released from hemolyzed red blood cells, accumulates in the brain after ICH and is associated with secondary neuronal injury and death. Researchers have found that deferoxamine, an iron chelator, provides neuroprotection and improves recovery after experimental ICH. The drug also has anti-inflammatory, antiapoptotic, and BP-lowering effects. Deferoxamine has been approved since the 1960s.
Magdy H. Selim, MD, PhD, a neurologist at Beth Israel Deaconess Medical Center in Boston, and colleagues hypothesized that treatment with deferoxamine could improve outcomes in patients with ICH. The researchers conducted a phase 2 clinical trial to evaluate whether deferoxamine should be studied in a phase 3 efficacy trial. In their multicenter, double-blind study, Dr. Selim and his colleagues randomized patients with spontaneous supratentorial ICH in equal groups to 32 mg/kg per day of deferoxamine or saline placebo. Treatments were administered as intravenous infusions for 3 consecutive days, and therapy was initiated within 24 hours after ICH onset. The follow-up period was 6 months.
Eligible participants had an National Institutes of Health Stroke Scale score of 6 or higher, a Glasgow Coma Scale score greater than 6, and had been functionally independent before the hemorrhage. The researchers excluded patients with a secondary cause for ICH or coagulopathy.
The primary endpoint in the futility analysis was the proportion of participants with a good clinical outcome – defined as a modified Rankin Scale (mRS) score of 0-2 – at 90 days and 180 days. The secondary endpoint was good outcome, defined as an mRS score of 0-3, at 90 days. Safety endpoints included all deferoxamine-related adverse events until day 7 or discharge (whichever was earlier) and serious adverse events through day 90.
Dr. Selim and his colleagues enrolled 294 participants in their trial, 3 of whom did not receive treatment. Of these included participants, 147 (50.5%) were randomized to placebo and 144 (49.5%) were randomized to deferoxamine. Participants’ mean age was 60.3 years, and 38.5% of the population was female.
Overall, the two study arms did not differ significantly according to demographic and clinical characteristics, however, there were more nonwhite patients in the deferoxamine arm than in the placebo arm, however. In addition, thalamic hemorrhage and intraventricular hemorrhage were more common in the placebo-treated group and hemorrhages in the putamen and basal ganglia were more common in the deferoxamine-treated group.
The rates of adverse events were comparable between the two study arms. Dr. Selim and his colleagues found no unexpected safety issues. Mortality was low, and the 90-day and 180-day mortality rates were comparable between the two treatment arms.
Approximately 34% of deferoxamine-treated patients and 33% of placebo-treated patients had an mRS score of 0-2 at 90 days. The adjusted absolute risk difference between arms was 0.6%; this result did not surpass the predefined futility threshold. The risk difference between groups for mRS score of 0-2 at 180 days was 8.6% in favor of deferoxamine, which did surpass the futility threshold.
The risk difference for meeting the secondary endpoint was 6.2% in favor of deferoxamine; this result did not surpass the futility threshold. Patients in both treatment groups improved between day 90 and day 180. The likelihood of good outcome was approximately 10% higher in the deferoxamine group at day 90 and 26% higher in the deferoxamine group at day 180.
“It is futile to conduct a phase 3 trial with the anticipation that treatment with deferoxamine would improve outcome, defined as mRS score of 0-2 at 90 days,” said Dr. Selim. “These data, together with the data from MISTIE and CLEAR, suggest that ICH trials need to have a longer follow-up period to capture the full extent of recovery after ICH. Several of our secondary analyses tended to favor deferoxamine over the placebo arm and leave open the possibility that deferoxamine might lead to improved outcome at 180 days.”
The researchers received support from the NIH and the National Institute of Neurological Disorders and Stroke.
SOURCE: Selim MH et al. ISC 2019, Abstract LB22.
HONOLULU – (ICH), according to trial results described at the International Stroke Conference sponsored by the American Heart Association. However, the drug is safe and well tolerated and data suggest that it may improve outcomes at 180 days.
Animal studies indicate that iron, which is released from hemolyzed red blood cells, accumulates in the brain after ICH and is associated with secondary neuronal injury and death. Researchers have found that deferoxamine, an iron chelator, provides neuroprotection and improves recovery after experimental ICH. The drug also has anti-inflammatory, antiapoptotic, and BP-lowering effects. Deferoxamine has been approved since the 1960s.
Magdy H. Selim, MD, PhD, a neurologist at Beth Israel Deaconess Medical Center in Boston, and colleagues hypothesized that treatment with deferoxamine could improve outcomes in patients with ICH. The researchers conducted a phase 2 clinical trial to evaluate whether deferoxamine should be studied in a phase 3 efficacy trial. In their multicenter, double-blind study, Dr. Selim and his colleagues randomized patients with spontaneous supratentorial ICH in equal groups to 32 mg/kg per day of deferoxamine or saline placebo. Treatments were administered as intravenous infusions for 3 consecutive days, and therapy was initiated within 24 hours after ICH onset. The follow-up period was 6 months.
Eligible participants had an National Institutes of Health Stroke Scale score of 6 or higher, a Glasgow Coma Scale score greater than 6, and had been functionally independent before the hemorrhage. The researchers excluded patients with a secondary cause for ICH or coagulopathy.
The primary endpoint in the futility analysis was the proportion of participants with a good clinical outcome – defined as a modified Rankin Scale (mRS) score of 0-2 – at 90 days and 180 days. The secondary endpoint was good outcome, defined as an mRS score of 0-3, at 90 days. Safety endpoints included all deferoxamine-related adverse events until day 7 or discharge (whichever was earlier) and serious adverse events through day 90.
Dr. Selim and his colleagues enrolled 294 participants in their trial, 3 of whom did not receive treatment. Of these included participants, 147 (50.5%) were randomized to placebo and 144 (49.5%) were randomized to deferoxamine. Participants’ mean age was 60.3 years, and 38.5% of the population was female.
Overall, the two study arms did not differ significantly according to demographic and clinical characteristics, however, there were more nonwhite patients in the deferoxamine arm than in the placebo arm, however. In addition, thalamic hemorrhage and intraventricular hemorrhage were more common in the placebo-treated group and hemorrhages in the putamen and basal ganglia were more common in the deferoxamine-treated group.
The rates of adverse events were comparable between the two study arms. Dr. Selim and his colleagues found no unexpected safety issues. Mortality was low, and the 90-day and 180-day mortality rates were comparable between the two treatment arms.
Approximately 34% of deferoxamine-treated patients and 33% of placebo-treated patients had an mRS score of 0-2 at 90 days. The adjusted absolute risk difference between arms was 0.6%; this result did not surpass the predefined futility threshold. The risk difference between groups for mRS score of 0-2 at 180 days was 8.6% in favor of deferoxamine, which did surpass the futility threshold.
The risk difference for meeting the secondary endpoint was 6.2% in favor of deferoxamine; this result did not surpass the futility threshold. Patients in both treatment groups improved between day 90 and day 180. The likelihood of good outcome was approximately 10% higher in the deferoxamine group at day 90 and 26% higher in the deferoxamine group at day 180.
“It is futile to conduct a phase 3 trial with the anticipation that treatment with deferoxamine would improve outcome, defined as mRS score of 0-2 at 90 days,” said Dr. Selim. “These data, together with the data from MISTIE and CLEAR, suggest that ICH trials need to have a longer follow-up period to capture the full extent of recovery after ICH. Several of our secondary analyses tended to favor deferoxamine over the placebo arm and leave open the possibility that deferoxamine might lead to improved outcome at 180 days.”
The researchers received support from the NIH and the National Institute of Neurological Disorders and Stroke.
SOURCE: Selim MH et al. ISC 2019, Abstract LB22.
HONOLULU – (ICH), according to trial results described at the International Stroke Conference sponsored by the American Heart Association. However, the drug is safe and well tolerated and data suggest that it may improve outcomes at 180 days.
Animal studies indicate that iron, which is released from hemolyzed red blood cells, accumulates in the brain after ICH and is associated with secondary neuronal injury and death. Researchers have found that deferoxamine, an iron chelator, provides neuroprotection and improves recovery after experimental ICH. The drug also has anti-inflammatory, antiapoptotic, and BP-lowering effects. Deferoxamine has been approved since the 1960s.
Magdy H. Selim, MD, PhD, a neurologist at Beth Israel Deaconess Medical Center in Boston, and colleagues hypothesized that treatment with deferoxamine could improve outcomes in patients with ICH. The researchers conducted a phase 2 clinical trial to evaluate whether deferoxamine should be studied in a phase 3 efficacy trial. In their multicenter, double-blind study, Dr. Selim and his colleagues randomized patients with spontaneous supratentorial ICH in equal groups to 32 mg/kg per day of deferoxamine or saline placebo. Treatments were administered as intravenous infusions for 3 consecutive days, and therapy was initiated within 24 hours after ICH onset. The follow-up period was 6 months.
Eligible participants had an National Institutes of Health Stroke Scale score of 6 or higher, a Glasgow Coma Scale score greater than 6, and had been functionally independent before the hemorrhage. The researchers excluded patients with a secondary cause for ICH or coagulopathy.
The primary endpoint in the futility analysis was the proportion of participants with a good clinical outcome – defined as a modified Rankin Scale (mRS) score of 0-2 – at 90 days and 180 days. The secondary endpoint was good outcome, defined as an mRS score of 0-3, at 90 days. Safety endpoints included all deferoxamine-related adverse events until day 7 or discharge (whichever was earlier) and serious adverse events through day 90.
Dr. Selim and his colleagues enrolled 294 participants in their trial, 3 of whom did not receive treatment. Of these included participants, 147 (50.5%) were randomized to placebo and 144 (49.5%) were randomized to deferoxamine. Participants’ mean age was 60.3 years, and 38.5% of the population was female.
Overall, the two study arms did not differ significantly according to demographic and clinical characteristics, however, there were more nonwhite patients in the deferoxamine arm than in the placebo arm, however. In addition, thalamic hemorrhage and intraventricular hemorrhage were more common in the placebo-treated group and hemorrhages in the putamen and basal ganglia were more common in the deferoxamine-treated group.
The rates of adverse events were comparable between the two study arms. Dr. Selim and his colleagues found no unexpected safety issues. Mortality was low, and the 90-day and 180-day mortality rates were comparable between the two treatment arms.
Approximately 34% of deferoxamine-treated patients and 33% of placebo-treated patients had an mRS score of 0-2 at 90 days. The adjusted absolute risk difference between arms was 0.6%; this result did not surpass the predefined futility threshold. The risk difference between groups for mRS score of 0-2 at 180 days was 8.6% in favor of deferoxamine, which did surpass the futility threshold.
The risk difference for meeting the secondary endpoint was 6.2% in favor of deferoxamine; this result did not surpass the futility threshold. Patients in both treatment groups improved between day 90 and day 180. The likelihood of good outcome was approximately 10% higher in the deferoxamine group at day 90 and 26% higher in the deferoxamine group at day 180.
“It is futile to conduct a phase 3 trial with the anticipation that treatment with deferoxamine would improve outcome, defined as mRS score of 0-2 at 90 days,” said Dr. Selim. “These data, together with the data from MISTIE and CLEAR, suggest that ICH trials need to have a longer follow-up period to capture the full extent of recovery after ICH. Several of our secondary analyses tended to favor deferoxamine over the placebo arm and leave open the possibility that deferoxamine might lead to improved outcome at 180 days.”
The researchers received support from the NIH and the National Institute of Neurological Disorders and Stroke.
SOURCE: Selim MH et al. ISC 2019, Abstract LB22.
REPORTING FROM ISC 2019
Key clinical point: Deferoxamine does not improve disability at 90 days after intracranial hemorrhage.
Major finding: Approximately one-third of patients in both treatment groups had a good outcome.
Study details: A multicenter, randomized, double-blind study of 294 participants with intracranial hemorrhage.
Disclosures: The National Institutes of Health and National Institute of Neurological Disorders and Stroke supported this study.
Source: Selim MH et al. ISC 2019, Abstract LB22.
Vaccination and antiviral treatment do not affect stroke risk following shingles
HONOLULU – according to findings from a retrospective study of Medicare beneficiaries with shingles and ischemic stroke.
The findings suggest that primary prevention of shingles through vaccination might be the most effective approach to prevent shingles-associated acute ischemic stroke, said the researchers, who presented the study at the International Stroke Conference sponsored by the American Heart Association.
Almost one in three people in the United States will develop shingles, also known as herpes zoster, in their lifetime, according to the Centers for Disease Control and Prevention. Previous research has not simultaneously examined the effect of shingles vaccination and antiviral treatment following shingles onset on the risk of acute ischemic stroke.
Quanhe Yang, PhD, a senior scientist at the CDC, and his colleagues examined data for 35,186 Medicare fee-for-service beneficiaries who were 66 years or older, diagnosed with shingles during 2008-2014, and diagnosed with acute ischemic stroke within a year of shingles diagnosis. Using a self-controlled case series design, the investigators analyzed the association between shingles and stroke. Dr. Yang and his colleagues estimated the incident rate ratio (IRR) by comparing the incidence of stroke during risk periods (i.e., periods following shingles), compared with control periods. To minimize confounding by age, they restricted their analyses to approximately 365 days from the shingles index date.
To investigate how vaccination against shingles with Zostavax and antiviral treatment following shingles affected stroke risk, the researchers classified beneficiaries into the following four groups: Group 1 had no vaccination and no antiviral treatment (49% of beneficiaries), Group 2 had vaccination only (9%), Group 3 had antiviral treatment only (34%), and Group 4 had vaccination and antiviral treatment (8%). The researchers tested for interaction to examine the changes in IRRs across the four groups.
IRRs for stroke progressively declined as time passed from the index shingles date, from 1.61 at 0-14 days following shingles to 1.35 at 15-30 days, 1.16 at 31-90 days, and 1.05 at 91-180 days. The researchers found no evidence that shingles vaccination and antiviral treatment modified the risk of acute ischemic stroke. The association between shingles and risk for acute ischemic stroke was consistent across age groups (i.e., 66-74 years, 75-84 years, and 85 years or older), sex, and race (i.e., non-Hispanic white, non-Hispanic black, and Hispanic, other).
One of the study’s strengths was that its sample was a large national cohort of Medicare fee-for-service beneficiaries, Dr. Yang said. In addition, the study design eliminated all fixed confounding effects. Potential weaknesses, however, included the fact that herpes zoster diagnosis was based on administrative data and that the vaccine’s efficacy declines over time.
The findings suggest that the importance of following the recommended shingles vaccination protocol in the prevention of shingles, Dr. Yang said. Shingrix, a vaccine that the Food and Drug Administration approved in 2017, prevents shingles with an efficacy greater than 90%, he added.
The investigators reported no funding source or disclosures for this study.
SOURCE: Yang Q et al. Circulation. 2019;50(Suppl_1): Abstract 39
HONOLULU – according to findings from a retrospective study of Medicare beneficiaries with shingles and ischemic stroke.
The findings suggest that primary prevention of shingles through vaccination might be the most effective approach to prevent shingles-associated acute ischemic stroke, said the researchers, who presented the study at the International Stroke Conference sponsored by the American Heart Association.
Almost one in three people in the United States will develop shingles, also known as herpes zoster, in their lifetime, according to the Centers for Disease Control and Prevention. Previous research has not simultaneously examined the effect of shingles vaccination and antiviral treatment following shingles onset on the risk of acute ischemic stroke.
Quanhe Yang, PhD, a senior scientist at the CDC, and his colleagues examined data for 35,186 Medicare fee-for-service beneficiaries who were 66 years or older, diagnosed with shingles during 2008-2014, and diagnosed with acute ischemic stroke within a year of shingles diagnosis. Using a self-controlled case series design, the investigators analyzed the association between shingles and stroke. Dr. Yang and his colleagues estimated the incident rate ratio (IRR) by comparing the incidence of stroke during risk periods (i.e., periods following shingles), compared with control periods. To minimize confounding by age, they restricted their analyses to approximately 365 days from the shingles index date.
To investigate how vaccination against shingles with Zostavax and antiviral treatment following shingles affected stroke risk, the researchers classified beneficiaries into the following four groups: Group 1 had no vaccination and no antiviral treatment (49% of beneficiaries), Group 2 had vaccination only (9%), Group 3 had antiviral treatment only (34%), and Group 4 had vaccination and antiviral treatment (8%). The researchers tested for interaction to examine the changes in IRRs across the four groups.
IRRs for stroke progressively declined as time passed from the index shingles date, from 1.61 at 0-14 days following shingles to 1.35 at 15-30 days, 1.16 at 31-90 days, and 1.05 at 91-180 days. The researchers found no evidence that shingles vaccination and antiviral treatment modified the risk of acute ischemic stroke. The association between shingles and risk for acute ischemic stroke was consistent across age groups (i.e., 66-74 years, 75-84 years, and 85 years or older), sex, and race (i.e., non-Hispanic white, non-Hispanic black, and Hispanic, other).
One of the study’s strengths was that its sample was a large national cohort of Medicare fee-for-service beneficiaries, Dr. Yang said. In addition, the study design eliminated all fixed confounding effects. Potential weaknesses, however, included the fact that herpes zoster diagnosis was based on administrative data and that the vaccine’s efficacy declines over time.
The findings suggest that the importance of following the recommended shingles vaccination protocol in the prevention of shingles, Dr. Yang said. Shingrix, a vaccine that the Food and Drug Administration approved in 2017, prevents shingles with an efficacy greater than 90%, he added.
The investigators reported no funding source or disclosures for this study.
SOURCE: Yang Q et al. Circulation. 2019;50(Suppl_1): Abstract 39
HONOLULU – according to findings from a retrospective study of Medicare beneficiaries with shingles and ischemic stroke.
The findings suggest that primary prevention of shingles through vaccination might be the most effective approach to prevent shingles-associated acute ischemic stroke, said the researchers, who presented the study at the International Stroke Conference sponsored by the American Heart Association.
Almost one in three people in the United States will develop shingles, also known as herpes zoster, in their lifetime, according to the Centers for Disease Control and Prevention. Previous research has not simultaneously examined the effect of shingles vaccination and antiviral treatment following shingles onset on the risk of acute ischemic stroke.
Quanhe Yang, PhD, a senior scientist at the CDC, and his colleagues examined data for 35,186 Medicare fee-for-service beneficiaries who were 66 years or older, diagnosed with shingles during 2008-2014, and diagnosed with acute ischemic stroke within a year of shingles diagnosis. Using a self-controlled case series design, the investigators analyzed the association between shingles and stroke. Dr. Yang and his colleagues estimated the incident rate ratio (IRR) by comparing the incidence of stroke during risk periods (i.e., periods following shingles), compared with control periods. To minimize confounding by age, they restricted their analyses to approximately 365 days from the shingles index date.
To investigate how vaccination against shingles with Zostavax and antiviral treatment following shingles affected stroke risk, the researchers classified beneficiaries into the following four groups: Group 1 had no vaccination and no antiviral treatment (49% of beneficiaries), Group 2 had vaccination only (9%), Group 3 had antiviral treatment only (34%), and Group 4 had vaccination and antiviral treatment (8%). The researchers tested for interaction to examine the changes in IRRs across the four groups.
IRRs for stroke progressively declined as time passed from the index shingles date, from 1.61 at 0-14 days following shingles to 1.35 at 15-30 days, 1.16 at 31-90 days, and 1.05 at 91-180 days. The researchers found no evidence that shingles vaccination and antiviral treatment modified the risk of acute ischemic stroke. The association between shingles and risk for acute ischemic stroke was consistent across age groups (i.e., 66-74 years, 75-84 years, and 85 years or older), sex, and race (i.e., non-Hispanic white, non-Hispanic black, and Hispanic, other).
One of the study’s strengths was that its sample was a large national cohort of Medicare fee-for-service beneficiaries, Dr. Yang said. In addition, the study design eliminated all fixed confounding effects. Potential weaknesses, however, included the fact that herpes zoster diagnosis was based on administrative data and that the vaccine’s efficacy declines over time.
The findings suggest that the importance of following the recommended shingles vaccination protocol in the prevention of shingles, Dr. Yang said. Shingrix, a vaccine that the Food and Drug Administration approved in 2017, prevents shingles with an efficacy greater than 90%, he added.
The investigators reported no funding source or disclosures for this study.
SOURCE: Yang Q et al. Circulation. 2019;50(Suppl_1): Abstract 39
REPORTING FROM ISC 2019
Key clinical point: After a patient develops shingles, prior vaccination or treatment with antiviral medication does not change the risk of acute ischemic stroke.
Major finding: Stroke incidence increased by 61% within 14 days after shingles onset.
Study details: A self-controlled case series of 35,186 Medicare beneficiaries with shingles and acute ischemic stroke.
Disclosures: The authors reported no funding source or disclosures for this study.
Source: Yang Q et al. Circulation. 2019;50(Suppl_1), Abstract 39
Most U.S. tPA-eligible stroke patients now get treated within an hour
HONOLULU – The speed at which eligible U.S. patients with acute ischemic stroke receive thrombolytic therapy has surged in recent years, and .
By the second half of last year, 75% of acute ischemic stroke patients treated at any of the 913 U.S. hospitals in the Get With The Guidelines-Stroke program received intravenous tissue plasminogen activator (tPA; Alteplase) within 60 minutes of their hospital arrival (their door-to-needle time (DTN), and 52% received tPA with a DTN time of 45 minutes or less. These levels met the treatment-speed goals set by the second phase of the Target: Stroke program, which called for delivering tPA to 75% of appropriate stroke patients within a DTN time of 60 minutes, and within 45 minutes in at least 50% of patients, Gregg C. Fonarow, MD, and his associates reported at the International Stroke Conference, sponsored by the American Heart Association.
The analyses they reported also documented how these most recent gains in thrombolytic speed played out in improved patient outcomes. During phase 2 of Target: Stroke, which ran from January 2014 to September 2018, 85,078 U.S. patients received tPA at one of the participating hospitals. During those 4 years, the rate of in-hospital mortality was 6.0%, half the patients were discharged home, 53% could ambulate independently, and the rate of intracerebral hemorrhage (ICH) was 3.5%. The researchers compared these clinical event rates with the rates from 24,603 tPA-treated patients during 2003-2009, before the Target: Stroke campaign began. After adjustment for many potential confounders, the more recently treated cohort had a 31% relative risk reduction in in-hospital mortality, a 43% relative increase in being discharged home, a 40% relative increase in independent ambulation, and a 32% relative risk reduction in the rate of symptomatic ICH. All these between-group differences were statistically significant.
“We were hoping that, by improving DTN times we could achieve improved outcomes, but often in quality-improvement research – even when the process of care improves – the gains in outcomes don’t necessarily match expectations. Fortunately, with Target: Stroke, the remarkable improvements in timely treatment translated to remarkable improvements in clinical outcomes,” Dr. Fonarow said in an interview. “These are substantial, clinically relevant improvements in clinical outcomes for patients with acute ischemic stroke. As a result of the program, more than 100,000 acute ischemic stroke patients received much more timely acute ischemic stroke care and achieved far better clinical outcomes.”
During the 2003-2018 period reviewed, the percentage of presenting acute ischemic stroke patients who received tPA treatment at the 913 Get With The Guidelines hospitals that participated in the Target: Stroke program (and so had reviewable data) throughout all three periods rose from 6% during 2003-2009 (prestudy) to 8% during 2010-2013 (phase 1), and to 12% during 2014-2018 (phase 2). The percentages of these patients who received the drug within 60 minutes were 27% during 2003-2009, 43% during 2010-2013, and 68% during the entire 2014-2018 period, culminating in the 75% rate during July-September 2018, reported Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Fonarow attributed the drop in the rate of ICH – from 5.7% during 2003-2009, to 4.4% during 2010-2013, and down to 3.5% during 2014-2018 – to the faster delivery of tPA. “With faster treatment, there is less ischemic brain and vascular damage and thus a lower likelihood of ICH as a complication of tPA,” he explained.
The Target: Stroke program achieved these gains in speedier thrombolytic treatment (and better recognition of eligible patients) through educational and promotional activities including dissemination of best practices. Notable best practices have included EMS prenotification of hospitals before they arrive with a stroke patient, direct transport of patients to a brain imaging scanner, premix of tPA, initiation of tPA in the brain imaging suite, and prompt data feedback, Dr. Fonarow said.
The Get With The Guidelines-Stroke and Target: Stroke programs now involve more than 2,100 U.S. hospitals, and they are able to deliver emergency care to roughly 70% of U.S. acute ischemic stroke patients, he noted.
With achievement of Target: Stroke’s phase 2 goals, the program announced its launch of a third phase, with new treatment goals: Initiation of thrombolytic treatment to 85% of eligible patients within 60 minutes, to 75% within 45 minutes, and to 50% within 30 minutes. The phase 3 Target: Stroke program also for the first time includes treatment goals for delivery of endovascular thrombectomy treatment.
SOURCE: Fonarow GC et al. ISC 2019, Abstract LBP9.
The Target: Stroke and Get With The Guidelines-Stroke programs should be commended for the very impressive achievements they have made in improved delivery of thrombolytic therapy to acute ischemic stroke patients. What’s happened over the past decade in the speed of delivery of tissue plasminogen activator for treating U.S. stroke patients has been a real success story.
Programs like Get With The Guidelines and Target: Stroke have proven their value, but a significant barrier remains to bringing this program to all U.S. stroke patients and to all U.S. hospitals that treat stroke patients. That barrier is resources. Participating hospitals need to meet certain data-collection standards, but some U.S. hospitals do not have the resources to do this.
Bruce Ovbiagele, MD , is a neurologist and chief of staff for the San Francisco Veterans Affairs Health Care System. He had no disclosures. He made these comments in an interview.
The Target: Stroke and Get With The Guidelines-Stroke programs should be commended for the very impressive achievements they have made in improved delivery of thrombolytic therapy to acute ischemic stroke patients. What’s happened over the past decade in the speed of delivery of tissue plasminogen activator for treating U.S. stroke patients has been a real success story.
Programs like Get With The Guidelines and Target: Stroke have proven their value, but a significant barrier remains to bringing this program to all U.S. stroke patients and to all U.S. hospitals that treat stroke patients. That barrier is resources. Participating hospitals need to meet certain data-collection standards, but some U.S. hospitals do not have the resources to do this.
Bruce Ovbiagele, MD , is a neurologist and chief of staff for the San Francisco Veterans Affairs Health Care System. He had no disclosures. He made these comments in an interview.
The Target: Stroke and Get With The Guidelines-Stroke programs should be commended for the very impressive achievements they have made in improved delivery of thrombolytic therapy to acute ischemic stroke patients. What’s happened over the past decade in the speed of delivery of tissue plasminogen activator for treating U.S. stroke patients has been a real success story.
Programs like Get With The Guidelines and Target: Stroke have proven their value, but a significant barrier remains to bringing this program to all U.S. stroke patients and to all U.S. hospitals that treat stroke patients. That barrier is resources. Participating hospitals need to meet certain data-collection standards, but some U.S. hospitals do not have the resources to do this.
Bruce Ovbiagele, MD , is a neurologist and chief of staff for the San Francisco Veterans Affairs Health Care System. He had no disclosures. He made these comments in an interview.
HONOLULU – The speed at which eligible U.S. patients with acute ischemic stroke receive thrombolytic therapy has surged in recent years, and .
By the second half of last year, 75% of acute ischemic stroke patients treated at any of the 913 U.S. hospitals in the Get With The Guidelines-Stroke program received intravenous tissue plasminogen activator (tPA; Alteplase) within 60 minutes of their hospital arrival (their door-to-needle time (DTN), and 52% received tPA with a DTN time of 45 minutes or less. These levels met the treatment-speed goals set by the second phase of the Target: Stroke program, which called for delivering tPA to 75% of appropriate stroke patients within a DTN time of 60 minutes, and within 45 minutes in at least 50% of patients, Gregg C. Fonarow, MD, and his associates reported at the International Stroke Conference, sponsored by the American Heart Association.
The analyses they reported also documented how these most recent gains in thrombolytic speed played out in improved patient outcomes. During phase 2 of Target: Stroke, which ran from January 2014 to September 2018, 85,078 U.S. patients received tPA at one of the participating hospitals. During those 4 years, the rate of in-hospital mortality was 6.0%, half the patients were discharged home, 53% could ambulate independently, and the rate of intracerebral hemorrhage (ICH) was 3.5%. The researchers compared these clinical event rates with the rates from 24,603 tPA-treated patients during 2003-2009, before the Target: Stroke campaign began. After adjustment for many potential confounders, the more recently treated cohort had a 31% relative risk reduction in in-hospital mortality, a 43% relative increase in being discharged home, a 40% relative increase in independent ambulation, and a 32% relative risk reduction in the rate of symptomatic ICH. All these between-group differences were statistically significant.
“We were hoping that, by improving DTN times we could achieve improved outcomes, but often in quality-improvement research – even when the process of care improves – the gains in outcomes don’t necessarily match expectations. Fortunately, with Target: Stroke, the remarkable improvements in timely treatment translated to remarkable improvements in clinical outcomes,” Dr. Fonarow said in an interview. “These are substantial, clinically relevant improvements in clinical outcomes for patients with acute ischemic stroke. As a result of the program, more than 100,000 acute ischemic stroke patients received much more timely acute ischemic stroke care and achieved far better clinical outcomes.”
During the 2003-2018 period reviewed, the percentage of presenting acute ischemic stroke patients who received tPA treatment at the 913 Get With The Guidelines hospitals that participated in the Target: Stroke program (and so had reviewable data) throughout all three periods rose from 6% during 2003-2009 (prestudy) to 8% during 2010-2013 (phase 1), and to 12% during 2014-2018 (phase 2). The percentages of these patients who received the drug within 60 minutes were 27% during 2003-2009, 43% during 2010-2013, and 68% during the entire 2014-2018 period, culminating in the 75% rate during July-September 2018, reported Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Fonarow attributed the drop in the rate of ICH – from 5.7% during 2003-2009, to 4.4% during 2010-2013, and down to 3.5% during 2014-2018 – to the faster delivery of tPA. “With faster treatment, there is less ischemic brain and vascular damage and thus a lower likelihood of ICH as a complication of tPA,” he explained.
The Target: Stroke program achieved these gains in speedier thrombolytic treatment (and better recognition of eligible patients) through educational and promotional activities including dissemination of best practices. Notable best practices have included EMS prenotification of hospitals before they arrive with a stroke patient, direct transport of patients to a brain imaging scanner, premix of tPA, initiation of tPA in the brain imaging suite, and prompt data feedback, Dr. Fonarow said.
The Get With The Guidelines-Stroke and Target: Stroke programs now involve more than 2,100 U.S. hospitals, and they are able to deliver emergency care to roughly 70% of U.S. acute ischemic stroke patients, he noted.
With achievement of Target: Stroke’s phase 2 goals, the program announced its launch of a third phase, with new treatment goals: Initiation of thrombolytic treatment to 85% of eligible patients within 60 minutes, to 75% within 45 minutes, and to 50% within 30 minutes. The phase 3 Target: Stroke program also for the first time includes treatment goals for delivery of endovascular thrombectomy treatment.
SOURCE: Fonarow GC et al. ISC 2019, Abstract LBP9.
HONOLULU – The speed at which eligible U.S. patients with acute ischemic stroke receive thrombolytic therapy has surged in recent years, and .
By the second half of last year, 75% of acute ischemic stroke patients treated at any of the 913 U.S. hospitals in the Get With The Guidelines-Stroke program received intravenous tissue plasminogen activator (tPA; Alteplase) within 60 minutes of their hospital arrival (their door-to-needle time (DTN), and 52% received tPA with a DTN time of 45 minutes or less. These levels met the treatment-speed goals set by the second phase of the Target: Stroke program, which called for delivering tPA to 75% of appropriate stroke patients within a DTN time of 60 minutes, and within 45 minutes in at least 50% of patients, Gregg C. Fonarow, MD, and his associates reported at the International Stroke Conference, sponsored by the American Heart Association.
The analyses they reported also documented how these most recent gains in thrombolytic speed played out in improved patient outcomes. During phase 2 of Target: Stroke, which ran from January 2014 to September 2018, 85,078 U.S. patients received tPA at one of the participating hospitals. During those 4 years, the rate of in-hospital mortality was 6.0%, half the patients were discharged home, 53% could ambulate independently, and the rate of intracerebral hemorrhage (ICH) was 3.5%. The researchers compared these clinical event rates with the rates from 24,603 tPA-treated patients during 2003-2009, before the Target: Stroke campaign began. After adjustment for many potential confounders, the more recently treated cohort had a 31% relative risk reduction in in-hospital mortality, a 43% relative increase in being discharged home, a 40% relative increase in independent ambulation, and a 32% relative risk reduction in the rate of symptomatic ICH. All these between-group differences were statistically significant.
“We were hoping that, by improving DTN times we could achieve improved outcomes, but often in quality-improvement research – even when the process of care improves – the gains in outcomes don’t necessarily match expectations. Fortunately, with Target: Stroke, the remarkable improvements in timely treatment translated to remarkable improvements in clinical outcomes,” Dr. Fonarow said in an interview. “These are substantial, clinically relevant improvements in clinical outcomes for patients with acute ischemic stroke. As a result of the program, more than 100,000 acute ischemic stroke patients received much more timely acute ischemic stroke care and achieved far better clinical outcomes.”
During the 2003-2018 period reviewed, the percentage of presenting acute ischemic stroke patients who received tPA treatment at the 913 Get With The Guidelines hospitals that participated in the Target: Stroke program (and so had reviewable data) throughout all three periods rose from 6% during 2003-2009 (prestudy) to 8% during 2010-2013 (phase 1), and to 12% during 2014-2018 (phase 2). The percentages of these patients who received the drug within 60 minutes were 27% during 2003-2009, 43% during 2010-2013, and 68% during the entire 2014-2018 period, culminating in the 75% rate during July-September 2018, reported Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Fonarow attributed the drop in the rate of ICH – from 5.7% during 2003-2009, to 4.4% during 2010-2013, and down to 3.5% during 2014-2018 – to the faster delivery of tPA. “With faster treatment, there is less ischemic brain and vascular damage and thus a lower likelihood of ICH as a complication of tPA,” he explained.
The Target: Stroke program achieved these gains in speedier thrombolytic treatment (and better recognition of eligible patients) through educational and promotional activities including dissemination of best practices. Notable best practices have included EMS prenotification of hospitals before they arrive with a stroke patient, direct transport of patients to a brain imaging scanner, premix of tPA, initiation of tPA in the brain imaging suite, and prompt data feedback, Dr. Fonarow said.
The Get With The Guidelines-Stroke and Target: Stroke programs now involve more than 2,100 U.S. hospitals, and they are able to deliver emergency care to roughly 70% of U.S. acute ischemic stroke patients, he noted.
With achievement of Target: Stroke’s phase 2 goals, the program announced its launch of a third phase, with new treatment goals: Initiation of thrombolytic treatment to 85% of eligible patients within 60 minutes, to 75% within 45 minutes, and to 50% within 30 minutes. The phase 3 Target: Stroke program also for the first time includes treatment goals for delivery of endovascular thrombectomy treatment.
SOURCE: Fonarow GC et al. ISC 2019, Abstract LBP9.
REPORTING FROM ISC 2019
Key clinical point: In late 2018, the Target: Stroke program met its phase 2 goal for timely delivery of thrombolytic therapy to acute ischemic stroke patients.
Major finding: In September 2018, 75% of eligible stroke patients underwent thrombolysis within 60 minutes of hospital arrival, and 52% within 45 minutes.
Study details: Review of data collected from 154,221 U.S. stroke patients treated with thrombolysis during 2003-2018.
Disclosures: Target: Stroke has received funding from Boehringer Ingelheim, Janssen, Bristol-Myers Squibb/Sanofi, and Merck. Dr. Fonarow had no relevant disclosures.
Source: Fonarow GC et al. ISC 2019, Abstract LBP9.
Cilostazol plus aspirin or clopidogrel reduces the risk of recurrent stroke
HONOLULU – The combination also entails a similar risk of major bleeding, compared with aspirin and clopidogrel alone, according to results from the Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com).
Dual-antiplatelet therapy with aspirin and clopidogrel reduced the rate of recurrent stroke in previous studies. The benefit of this drug combination is relatively short-lived, however, and long-term concomitant use of aspirin and clopidogrel entails a risk of major bleeding. Other data have indicated that cilostazol, which is approved by the Food and Drug Administration to alleviate intermittent claudication in patients with peripheral vascular disease, prevents stroke recurrence without increasing the incidence of serious bleeding, compared with aspirin, said Kazunori Toyoda, MD, PhD, who presented the results of the CSPS.com trial at the International Stroke Conference sponsored by the American Heart Association.
Dr. Toyoda of the National Cerebral and Cardiovascular Center in Osaka, Japan, and his colleagues randomized 1,879 high-risk patients at 8-180 days after the onset of noncardioembolic ischemic stroke identified on MRI to receive 81 or 100 mg aspirin or 50 or 75 mg clopidogrel alone, or a combination of cilostazol 100 mg twice daily with aspirin or clopidogrel. They conducted their open-label, parallel-group trial at 292 sites in Japan from December 2013 through March 2017.
To be considered at high risk, participants had to meet one or more of the following criteria: 50% or greater stenosis of a major intracranial artery, 50% or greater stenosis of an extracranial artery, and two or more vascular risk factors. The trial’s primary efficacy outcome was the first recurrence of ischemic stroke. Safety outcomes included severe or life-threatening bleeding.
The investigators ended the trial early because of a delay in recruiting patients. They enrolled 1,884 and randomized 1,879 of an anticipated 4,000 patients. At randomization, 41% in the dual-therapy group received aspirin and 59% clopidogrel, and in the monotherapy group, 40% received aspirin and 60% clopidogrel. Baseline characteristics were similar between the treatment groups. The population’s mean age was 70. Approximately 30% of patients were women.
During a median follow-up period of 17 months, ischemic stroke recurred in 29 of 932 patients receiving dual therapy including cilostazol for an annual rate of 2.2% and in 64 of 947 patients receiving monotherapy for an annual rate of 4.5% (hazard ratio, 0.49; 95% confidence interval, 0.31-0.76; P = .001). Severe or life-threatening bleeding occurred in 8 patients (0.6% per year) receiving dual therapy and 13 patients (0.9% per year) receiving monotherapy (HR, 0.66; 95% CI, 0.27-1.60; P = .354).
The study was funded by Otsuka Pharmaceutical, which manufactures cilostazol. Dr. Toyoda reported receiving support from Bayer Yakuhin, Daiichi Sankyo, Bristol-Myers Squibb, and Nippon Boehringer Ingelheim.
SOURCE: Toyoda K et al. ISC 2019, Abstract LB3.
HONOLULU – The combination also entails a similar risk of major bleeding, compared with aspirin and clopidogrel alone, according to results from the Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com).
Dual-antiplatelet therapy with aspirin and clopidogrel reduced the rate of recurrent stroke in previous studies. The benefit of this drug combination is relatively short-lived, however, and long-term concomitant use of aspirin and clopidogrel entails a risk of major bleeding. Other data have indicated that cilostazol, which is approved by the Food and Drug Administration to alleviate intermittent claudication in patients with peripheral vascular disease, prevents stroke recurrence without increasing the incidence of serious bleeding, compared with aspirin, said Kazunori Toyoda, MD, PhD, who presented the results of the CSPS.com trial at the International Stroke Conference sponsored by the American Heart Association.
Dr. Toyoda of the National Cerebral and Cardiovascular Center in Osaka, Japan, and his colleagues randomized 1,879 high-risk patients at 8-180 days after the onset of noncardioembolic ischemic stroke identified on MRI to receive 81 or 100 mg aspirin or 50 or 75 mg clopidogrel alone, or a combination of cilostazol 100 mg twice daily with aspirin or clopidogrel. They conducted their open-label, parallel-group trial at 292 sites in Japan from December 2013 through March 2017.
To be considered at high risk, participants had to meet one or more of the following criteria: 50% or greater stenosis of a major intracranial artery, 50% or greater stenosis of an extracranial artery, and two or more vascular risk factors. The trial’s primary efficacy outcome was the first recurrence of ischemic stroke. Safety outcomes included severe or life-threatening bleeding.
The investigators ended the trial early because of a delay in recruiting patients. They enrolled 1,884 and randomized 1,879 of an anticipated 4,000 patients. At randomization, 41% in the dual-therapy group received aspirin and 59% clopidogrel, and in the monotherapy group, 40% received aspirin and 60% clopidogrel. Baseline characteristics were similar between the treatment groups. The population’s mean age was 70. Approximately 30% of patients were women.
During a median follow-up period of 17 months, ischemic stroke recurred in 29 of 932 patients receiving dual therapy including cilostazol for an annual rate of 2.2% and in 64 of 947 patients receiving monotherapy for an annual rate of 4.5% (hazard ratio, 0.49; 95% confidence interval, 0.31-0.76; P = .001). Severe or life-threatening bleeding occurred in 8 patients (0.6% per year) receiving dual therapy and 13 patients (0.9% per year) receiving monotherapy (HR, 0.66; 95% CI, 0.27-1.60; P = .354).
The study was funded by Otsuka Pharmaceutical, which manufactures cilostazol. Dr. Toyoda reported receiving support from Bayer Yakuhin, Daiichi Sankyo, Bristol-Myers Squibb, and Nippon Boehringer Ingelheim.
SOURCE: Toyoda K et al. ISC 2019, Abstract LB3.
HONOLULU – The combination also entails a similar risk of major bleeding, compared with aspirin and clopidogrel alone, according to results from the Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com).
Dual-antiplatelet therapy with aspirin and clopidogrel reduced the rate of recurrent stroke in previous studies. The benefit of this drug combination is relatively short-lived, however, and long-term concomitant use of aspirin and clopidogrel entails a risk of major bleeding. Other data have indicated that cilostazol, which is approved by the Food and Drug Administration to alleviate intermittent claudication in patients with peripheral vascular disease, prevents stroke recurrence without increasing the incidence of serious bleeding, compared with aspirin, said Kazunori Toyoda, MD, PhD, who presented the results of the CSPS.com trial at the International Stroke Conference sponsored by the American Heart Association.
Dr. Toyoda of the National Cerebral and Cardiovascular Center in Osaka, Japan, and his colleagues randomized 1,879 high-risk patients at 8-180 days after the onset of noncardioembolic ischemic stroke identified on MRI to receive 81 or 100 mg aspirin or 50 or 75 mg clopidogrel alone, or a combination of cilostazol 100 mg twice daily with aspirin or clopidogrel. They conducted their open-label, parallel-group trial at 292 sites in Japan from December 2013 through March 2017.
To be considered at high risk, participants had to meet one or more of the following criteria: 50% or greater stenosis of a major intracranial artery, 50% or greater stenosis of an extracranial artery, and two or more vascular risk factors. The trial’s primary efficacy outcome was the first recurrence of ischemic stroke. Safety outcomes included severe or life-threatening bleeding.
The investigators ended the trial early because of a delay in recruiting patients. They enrolled 1,884 and randomized 1,879 of an anticipated 4,000 patients. At randomization, 41% in the dual-therapy group received aspirin and 59% clopidogrel, and in the monotherapy group, 40% received aspirin and 60% clopidogrel. Baseline characteristics were similar between the treatment groups. The population’s mean age was 70. Approximately 30% of patients were women.
During a median follow-up period of 17 months, ischemic stroke recurred in 29 of 932 patients receiving dual therapy including cilostazol for an annual rate of 2.2% and in 64 of 947 patients receiving monotherapy for an annual rate of 4.5% (hazard ratio, 0.49; 95% confidence interval, 0.31-0.76; P = .001). Severe or life-threatening bleeding occurred in 8 patients (0.6% per year) receiving dual therapy and 13 patients (0.9% per year) receiving monotherapy (HR, 0.66; 95% CI, 0.27-1.60; P = .354).
The study was funded by Otsuka Pharmaceutical, which manufactures cilostazol. Dr. Toyoda reported receiving support from Bayer Yakuhin, Daiichi Sankyo, Bristol-Myers Squibb, and Nippon Boehringer Ingelheim.
SOURCE: Toyoda K et al. ISC 2019, Abstract LB3.
REPORTING FROM ISC
Key clinical point: Treating patients at high risk of recurrent stroke with cilostazol and aspirin or clopidogrel reduced the risk of recurrent stroke more than either aspirin or clopidogrel alone and was just as safe.
Major finding: Dual therapy with cilostazol and aspirin or clopidogrel reduced the risk of recurrent stroke by approximately half, compared with aspirin or clopidogrel alone.
Study details: A multicenter, randomized, open-label, parallel-group trial including 1,879 patients at high risk of recurrent stroke.
Disclosures: Otsuka Pharmaceutical funded the study. The presenter reported receiving support from Bayer Yakuhin, Daiichi Sankyo, Bristol-Myers Squibb, and Nippon Boehringer Ingelheim.
Source: Toyoda K et al. ISC 2019, Abstract LB3.
Intensive insulin added no benefit for hyperglycemia after ischemic stroke
HONOLULU – In patients who were hyperglycemic following an acute ischemic stroke, intensive insulin control using a continuous insulin drip and an aggressive blood glucose target of 80-130 mg/dL provided no incremental benefit in clinical outcome, compared with a more standard approach of serial, subcutaneous insulin injections and a moderate blood glucose target in a multicenter, U.S. trial with more than 1,100 patients.
The results also highlighted the potential downside to aggressive insulin treatment, with an associated 2.6% incidence of severe hypoglycemia, defined as blood glucose falling below 40 mg/dL, Karen C. Johnston, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“Our data suggest that subcutaneously administered insulin with a target blood glucose level of less than 180 mg/dL is the preferred treatment” because it produces similar efficacy without causing any episodes of severe hypoglycemia, concluded Dr. Johnston, professor and chair of neurology at the University of Virginia in Charlottesville. “There should be no further debate” over the potential superiority of a glucose target substantially below 180 mg/dL, she added in an interview.
Continuing to use a glucose target of less than 180 mg/dL and treating patients with subcutaneous insulin injections every 6 hours to achieve this will mean substantially less resource use and precludes the need for keeping patients in intensive care beds as is needed with an insulin drip, Dr. Johnston noted. A treatment target of less than 180 mg/dL is also consistent with the most recent American Heart Association stroke treatment guidelines, which listed a blood glucose target of 140-180 mg/dL as a class IIa recommendation (Stroke. 2018 March;49[3]:e66-99).
The SHINE (Stroke Hyperglycemia Insulin Network Effort) trial enrolled 1,151 adults diagnosed with an acute ischemic stroke at 63 U.S. centers during 2012-2018, excluding patients with type 1 diabetes. Patients had to enter the study within 12 hours of their last known well time, and with an elevated blood glucose level, above 110 mg/dL in patients with type 2 diabetes or at or above 150 mg/dL in other patients. The median glucose level of enrolled patients was about 188 mg/dL. Enrolled patients averaged 66 years old, and about 80% had type 2 diabetes. The median time from last known well to randomization was just over 7 hours. Almost two-thirds of the patients received thrombolytic treatment, and about 13% underwent thrombectomy.
During up to 72 hours of treatment following enrollment the patients in the standard-treatment arm showed a fairly steady average blood glucose level of 179 mg/dL; patients in the intensive arm showed a steady average of 118 mg/dL.
The study’s primary end point was the percentage of patients with a favorable outcome 90 days after enrollment based on their modified Rankin scale score at that time, with the scores that qualified for this end point varying depending on stroke severity at baseline. The percentage of patients achieving this was 20.5% among the intensive patients and 21.6% among those who received standard insulin treatment, a difference that was not statistically significant.
The findings left open the question of how to better manage acute ischemic stroke patients who present with hyperglycemia.
“Hyperglycemic stroke patients have worse outcomes than stroke patients without hyperglycemia. More aggressively treating the hyperglycemia did not help these patients, We need to figure out what will help them,” Dr. Johnson said.
SOURCE: Johnston KC et al. ISC 2019, Abstract LB1.
SHINE was a well-designed trial that was run with a high degree of rigor, and its results advance the field. The results left no doubt that the result was neutral, that , while resulting in an excess of severe hypoglycemia episodes.
Using a less intensive insulin regimen that does not require a continuous drip is easier. The question of how aggressive treatment needs to be when managing glucose in acute ischemic stroke patients is something that U.S. clinicians who care for stroke patients argue about virtually daily. At my center, Cedars-Sinai in Los Angeles, we have recently used an approach that blended standard insulin treatment with more aggressive treatment. The SHINE results may not be practice changing, but they will be argument changing. The new results will make a difference. We will now stop arguing. We now know what we need to do.
Patrick D. Lyden, MD , is professor and chair of neurology at Cedars-Sinai Medical Center in Los Angeles. He had no relevant disclosures. He made these comments in an interview.
SHINE was a well-designed trial that was run with a high degree of rigor, and its results advance the field. The results left no doubt that the result was neutral, that , while resulting in an excess of severe hypoglycemia episodes.
Using a less intensive insulin regimen that does not require a continuous drip is easier. The question of how aggressive treatment needs to be when managing glucose in acute ischemic stroke patients is something that U.S. clinicians who care for stroke patients argue about virtually daily. At my center, Cedars-Sinai in Los Angeles, we have recently used an approach that blended standard insulin treatment with more aggressive treatment. The SHINE results may not be practice changing, but they will be argument changing. The new results will make a difference. We will now stop arguing. We now know what we need to do.
Patrick D. Lyden, MD , is professor and chair of neurology at Cedars-Sinai Medical Center in Los Angeles. He had no relevant disclosures. He made these comments in an interview.
SHINE was a well-designed trial that was run with a high degree of rigor, and its results advance the field. The results left no doubt that the result was neutral, that , while resulting in an excess of severe hypoglycemia episodes.
Using a less intensive insulin regimen that does not require a continuous drip is easier. The question of how aggressive treatment needs to be when managing glucose in acute ischemic stroke patients is something that U.S. clinicians who care for stroke patients argue about virtually daily. At my center, Cedars-Sinai in Los Angeles, we have recently used an approach that blended standard insulin treatment with more aggressive treatment. The SHINE results may not be practice changing, but they will be argument changing. The new results will make a difference. We will now stop arguing. We now know what we need to do.
Patrick D. Lyden, MD , is professor and chair of neurology at Cedars-Sinai Medical Center in Los Angeles. He had no relevant disclosures. He made these comments in an interview.
HONOLULU – In patients who were hyperglycemic following an acute ischemic stroke, intensive insulin control using a continuous insulin drip and an aggressive blood glucose target of 80-130 mg/dL provided no incremental benefit in clinical outcome, compared with a more standard approach of serial, subcutaneous insulin injections and a moderate blood glucose target in a multicenter, U.S. trial with more than 1,100 patients.
The results also highlighted the potential downside to aggressive insulin treatment, with an associated 2.6% incidence of severe hypoglycemia, defined as blood glucose falling below 40 mg/dL, Karen C. Johnston, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“Our data suggest that subcutaneously administered insulin with a target blood glucose level of less than 180 mg/dL is the preferred treatment” because it produces similar efficacy without causing any episodes of severe hypoglycemia, concluded Dr. Johnston, professor and chair of neurology at the University of Virginia in Charlottesville. “There should be no further debate” over the potential superiority of a glucose target substantially below 180 mg/dL, she added in an interview.
Continuing to use a glucose target of less than 180 mg/dL and treating patients with subcutaneous insulin injections every 6 hours to achieve this will mean substantially less resource use and precludes the need for keeping patients in intensive care beds as is needed with an insulin drip, Dr. Johnston noted. A treatment target of less than 180 mg/dL is also consistent with the most recent American Heart Association stroke treatment guidelines, which listed a blood glucose target of 140-180 mg/dL as a class IIa recommendation (Stroke. 2018 March;49[3]:e66-99).
The SHINE (Stroke Hyperglycemia Insulin Network Effort) trial enrolled 1,151 adults diagnosed with an acute ischemic stroke at 63 U.S. centers during 2012-2018, excluding patients with type 1 diabetes. Patients had to enter the study within 12 hours of their last known well time, and with an elevated blood glucose level, above 110 mg/dL in patients with type 2 diabetes or at or above 150 mg/dL in other patients. The median glucose level of enrolled patients was about 188 mg/dL. Enrolled patients averaged 66 years old, and about 80% had type 2 diabetes. The median time from last known well to randomization was just over 7 hours. Almost two-thirds of the patients received thrombolytic treatment, and about 13% underwent thrombectomy.
During up to 72 hours of treatment following enrollment the patients in the standard-treatment arm showed a fairly steady average blood glucose level of 179 mg/dL; patients in the intensive arm showed a steady average of 118 mg/dL.
The study’s primary end point was the percentage of patients with a favorable outcome 90 days after enrollment based on their modified Rankin scale score at that time, with the scores that qualified for this end point varying depending on stroke severity at baseline. The percentage of patients achieving this was 20.5% among the intensive patients and 21.6% among those who received standard insulin treatment, a difference that was not statistically significant.
The findings left open the question of how to better manage acute ischemic stroke patients who present with hyperglycemia.
“Hyperglycemic stroke patients have worse outcomes than stroke patients without hyperglycemia. More aggressively treating the hyperglycemia did not help these patients, We need to figure out what will help them,” Dr. Johnson said.
SOURCE: Johnston KC et al. ISC 2019, Abstract LB1.
HONOLULU – In patients who were hyperglycemic following an acute ischemic stroke, intensive insulin control using a continuous insulin drip and an aggressive blood glucose target of 80-130 mg/dL provided no incremental benefit in clinical outcome, compared with a more standard approach of serial, subcutaneous insulin injections and a moderate blood glucose target in a multicenter, U.S. trial with more than 1,100 patients.
The results also highlighted the potential downside to aggressive insulin treatment, with an associated 2.6% incidence of severe hypoglycemia, defined as blood glucose falling below 40 mg/dL, Karen C. Johnston, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“Our data suggest that subcutaneously administered insulin with a target blood glucose level of less than 180 mg/dL is the preferred treatment” because it produces similar efficacy without causing any episodes of severe hypoglycemia, concluded Dr. Johnston, professor and chair of neurology at the University of Virginia in Charlottesville. “There should be no further debate” over the potential superiority of a glucose target substantially below 180 mg/dL, she added in an interview.
Continuing to use a glucose target of less than 180 mg/dL and treating patients with subcutaneous insulin injections every 6 hours to achieve this will mean substantially less resource use and precludes the need for keeping patients in intensive care beds as is needed with an insulin drip, Dr. Johnston noted. A treatment target of less than 180 mg/dL is also consistent with the most recent American Heart Association stroke treatment guidelines, which listed a blood glucose target of 140-180 mg/dL as a class IIa recommendation (Stroke. 2018 March;49[3]:e66-99).
The SHINE (Stroke Hyperglycemia Insulin Network Effort) trial enrolled 1,151 adults diagnosed with an acute ischemic stroke at 63 U.S. centers during 2012-2018, excluding patients with type 1 diabetes. Patients had to enter the study within 12 hours of their last known well time, and with an elevated blood glucose level, above 110 mg/dL in patients with type 2 diabetes or at or above 150 mg/dL in other patients. The median glucose level of enrolled patients was about 188 mg/dL. Enrolled patients averaged 66 years old, and about 80% had type 2 diabetes. The median time from last known well to randomization was just over 7 hours. Almost two-thirds of the patients received thrombolytic treatment, and about 13% underwent thrombectomy.
During up to 72 hours of treatment following enrollment the patients in the standard-treatment arm showed a fairly steady average blood glucose level of 179 mg/dL; patients in the intensive arm showed a steady average of 118 mg/dL.
The study’s primary end point was the percentage of patients with a favorable outcome 90 days after enrollment based on their modified Rankin scale score at that time, with the scores that qualified for this end point varying depending on stroke severity at baseline. The percentage of patients achieving this was 20.5% among the intensive patients and 21.6% among those who received standard insulin treatment, a difference that was not statistically significant.
The findings left open the question of how to better manage acute ischemic stroke patients who present with hyperglycemia.
“Hyperglycemic stroke patients have worse outcomes than stroke patients without hyperglycemia. More aggressively treating the hyperglycemia did not help these patients, We need to figure out what will help them,” Dr. Johnson said.
SOURCE: Johnston KC et al. ISC 2019, Abstract LB1.
REPORTING FROM ISC 2019
Key clinical point: Aggressive insulin management of hyperglycemia following an ischemic stroke gave no clinical benefit, compared with a standard approach.
Major finding: After 90 days, favorable outcomes occurred in 21% of patients on aggressive insulin treatment and 22% on standard treatment.
Study details: SHINE, a multicenter, randomized trial with 1,151 acute ischemic stroke patients.
Disclosures: SHINE received no commercial funding. Dr. Johnston had no disclosures.
Source: Johnston KC et al. ISC 2019, Abstract LB1.