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LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.
“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.
The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.
“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
MISTIE III showcases better ICH outcomes
Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.
However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.
The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.
When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.
“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.
She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
A message for acute-care clinicians
She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.
“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.
In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.
“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.
“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.
An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
More evidence needed to prove MISTIE’s hypothesis
According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.
Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.
Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.
But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.
“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.
Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.
LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.
“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.
The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.
“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
MISTIE III showcases better ICH outcomes
Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.
However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.
The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.
When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.
“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.
She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
A message for acute-care clinicians
She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.
“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.
In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.
“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.
“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.
An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
More evidence needed to prove MISTIE’s hypothesis
According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.
Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.
Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.
But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.
“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.
Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.
LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.
“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.
The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.
“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
MISTIE III showcases better ICH outcomes
Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.
However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.
The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.
When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.
“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.
She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
A message for acute-care clinicians
She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.
“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.
In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.
“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.
“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.
An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
More evidence needed to prove MISTIE’s hypothesis
According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.
Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.
Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.
But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.
“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.
Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.
REPORTING FROM ISC 2020