ISC 2015

NASHVILLE, TENN. – Results from three randomized controlled trials presented at the International Stroke Conference, plus the outcomes from a fourth trial first reported last fall, immediately established embolectomy as standard-of-care treatment for selected patients with acute ischemic stroke.

Stroke experts interviewed during the conference, however, said that making embolectomy routinely available to most U.S. stroke patients who would be candidates for the intervention will take months, if not years.

They envision challenges involving the availability of trained interventionalists, triage of patients to the right centers, and reimbursement issues as some of the obstacles to be dealt with before endovascular embolectomy aimed at removing intracerebral-artery occlusions in acute ischemic stroke patients becomes uniformly available.

Yet another challenge will arise when stroke-treatment groups that did not participate in the trials strive to replicate the success their colleagues reported by implementing the highly streamlined systems that were used in the trials for identifying appropriate stroke patients and for delivering treatment. Those systems were cited as an important reason why those studies succeeded in producing positive outcomes when similar embolectomy trials without the same efficiencies reported just a year or two ago failed to show benefit.

“The evidence makes it standard of care, but the challenge is that our systems are not set up. This is the big thing we will all go home to work on,” said Dr. Pooja Khatri, professor of neurology and director of acute stroke at the University of Cincinnati.

“You talk to everyone at this meeting, and what they want to go home and figure out is how can we deliver this care. It’s really challenging, at a myriad of levels,” said Dr. Colin P. Derdeyn, professor of neurology and director of the Center for Stroke and Cerebrovascular Disease at Washington University in St. Louis.

Growing endovascular availability

Arguably the most critical issue in rolling out endovascular stroke interventions more broadly is scaling up the number of centers that have the staff and systems in place to perform them. Clearly, the scope of providers able to deliver this treatment currently falls substantially short of what will be needed. “It’s kind of daunting to think about the [workforce] needs,” Dr. Khatri said in a talk at the conference, which was sponsored by the American Heart Association.

“In the United States, we’ve been building out a two-tier system, with comprehensive stroke centers capable of delivering this [endovascular embolectomy] treatment” and primary stroke centers capable of administering intravenous treatment with tissue plasminogen activator (TPA), the first treatment that patients eligible for embolectomy should receive, said Dr. Jeffrey L. Saver, professor of neurology and director of the stroke center at the University of California, Los Angeles, and lead investigator for one of the new embolectomy studies.

“Work groups have suggested about 60,000 U.S. stroke patients could potentially be treated with endovascular therapy, and we’d need about 300 comprehensive stroke centers to do this.” Dr. Saver estimated the current total of U.S. comprehensive stroke centers to be 75, a number that several others at the meeting pegged as more like 80, and they also noted that some centers are endovascular ready but have not received official comprehensive stroke center certification from the Joint Commission.

The extent to which availability of U.S. embolectomy remained limited through most of 2013 was apparent in data reported at the conference by Dr. Opeolu M. Adeoye, an emergency medicine physician and medical director of the telestroke program of the University of Cincinnati. During fiscal year 2013 (Oct. 2012 to Sept. 2013), 386,144 Medicare patients either older than 65 years or totally disabled had a primary hospital discharge diagnosis of stroke; of those, 5.1% had received thrombolytic therapy with intravenous TPA and 0.8% had undergone embolectomy. In a second analysis, he looked at stroke discharges and reperfusion treatments used in the 214 U.S. acute-care hospitals currently enrolled in StrokeNet, a program begun in 2013 by the National Institute of Neurological Disorders and Stroke to organize U.S. centers interested in participating in stroke trials.

During the same period, the 214 StrokeNet hospitals discharged 44,282 Medicare eligible patients who met the same age or disability criteria, with a TPA-treatment rate of 7.9% and an endovascular treatment rate of 2.2%. Although the StrokeNet hospitals treated roughly 11% of U.S. stroke patients in the specified demographic, they administered about 20% of the reperfusion treatment, Dr. Adeoye reported. He also highlighted that the 7.9% rate of TPA treatment among the StrokeNet hospitals correlated well with prior estimates that 6%-11% of stroke patients fulfill existing criteria for TPA treatment

A wide disparity existed in the rate of reperfusion use among StrokeNet hospitals. Sixty-seven hospitals, 31% of the StrokeNet group, treated at least 20 stroke patients with TPA during the study period, while 100 (47%) of the StrokeNet hospitals treated fewer than 10 acute stroke patients. The rate of those doing embolectomies was substantially lower, with 10 hospitals (5%) doing at least 20 endovascular procedures while 90% did fewer than 10.

Although Dr. Adeoye expressed confidence that the number of U.S. centers doing embolectomy cases will “change rapidly” following the new reports documenting the efficacy of the approach, he also acknowledged the challenges of growing the number of high-volume endovascular centers.

Centers that have been equivocal about embolectomy will now start doing it in a more concerted way, he predicted, but if cases get spread out and some sites do only a few patients a year, the quality of the procedures may suffer. “The more cases a site does, the better,” he noted, adding that regions that funnel all their stroke patients to a single endovascular site “do really well.”

“Right now, many hospitals want to do everything to get [fully] reimbursed and not send their patients down the line. There is a financial incentive to build up the stroke service at every hospital,” Dr. Derdeyn noted.

Another aspect to sorting out which centers start offering endovascular treatment will be the need to locate them in a rational way, as happened with trauma centers. Until now, placement of comprehensive stroke centers often depended on hospitals developing the capability as a marketing tool, noted Dr. Larry B. Goldstein, professor of neurology and director of the stroke center at Duke University in Durham, N.C. A hospital might achieve comprehensive stroke center certification, so a second center a few blocks away then follows suit seemingly to keep pace in a public-relations battle for cachet. The result has been an irrational clustering of centers with endovascular capability. He cited the situation in Cleveland, where comprehensive centers run by the Cleveland Clinic and Case Western stand a few dozen feet apart.

Challenges for triage

An analysis published last year by Dr. Adeoye and his colleagues showed that 56% of the U.S. population lived within a 60-minute drive of a hospital able to administer endovascular stroke treatment; by air, 85% had that access (Stroke 2014;45:3019-24). For TPA, 81% of people lived within a 60-minute drive of a center able to administer intravenous lytic treatment and 97% could reach these hospitals within an hour by air. While those numbers sound promising, though, fulfilling that potential depends on getting the right patients to the right hospitals.

Patient triage is perhaps the most vexing issue created by embolectomy’s success. For at least the short term, a limited number of centers will have the staffing and capacity to deliver endovascular embolectomy on a 24/7 basis to acute ischemic stroke patients who have a proximal blockage in a large cerebral artery. The relatively small number of sites able to offer embolectomy, and the much larger number of sites able to administer thrombolytic therapy with TPA, set the stage for some possible tension, or at least confusion, within communities over where an ambulance should bring an acute ischemic stroke patient.

“In some places they have trained the EMS [emergency medical services] to recognize severe strokes that are likely to benefit [from embolectomy], and they take those patients to places with endovascular capability. But there are some states with laws against doing this. There are major issues when EMS bypasses hospitals,” Dr. Derdeyn noted. “That’s the million-dollar question: How do you identify the stroke patients [with severe strokes who would benefit from embolectomy] and get them to where they need to go.” Like Dr. Adeoye, Dr. Derdeyn believes that endovascular treatment for stroke needs to be centralized at a relatively small number of high-volume centers.

“You can imagine that the fastest way to get stroke patients treated is to have them all go to one place, but that is much easier said than done,” Dr. Khatri said.

“Stent retrievers get cerebral arteries open, but that is not the biggest challenge. For the short term, the key issue is to get the correct patients to the correct hospitals where they can be treated by the correct team,” said Dr. Mayank Goyal, professor of diagnostic imaging at the University of Calgary (Alta.) and lead investigator for two of the three trials presented at the conference.

“You need a neurologist capable of deciding whether it really is a stroke, and pretty high-level imaging to identify the large-vessel occlusions that will benefit. Acquiring a CT angiography (CTA) image of the brain is a push-button process, but figuring out what the CTA says is not push button, especially the more sophisticated perfusion CT imaging to assess collateral circulation. I don’t see this capability happening in every catheterization laboratory,” Dr. Derdeyn said in an interview.

Another issue is volume. “Telemedicine may allow broader use of [more sophisticated] imaging, but if a place is only doing 20 endovascular procedures a year, they won’t have the best outcomes. Most small hospitals that today give patients TPA see 20 cases or fewer a year, and perhaps 5 patients will have a large-vessel occlusion,” Dr. Derdeyn said.

Before the new reports documenting the safety and efficacy of endovascular treatment, “we did not have the justification to bypass primary stroke centers and take patients directly to comprehensive stroke centers,” Dr. Khatri said. Now, “there is clear evidence that patients with severe strokes should not go to the nearby primary stroke center” but instead head directly for the centers capable of performing embolectomy. But Dr. Khatri also acknowledged that a complex calculation is needed to balance the trade off: Is it better to take a stroke patient more quickly to a nearby hospital that can only start TPA and perhaps later forward the patient to an embolectomy-ready hospital, or to transport the patient somewhat further to a facility able to deliver both TPA and embolectomy?

Dr. Khatri said that, in the Cincinnati area, “we have scheduled a retreat for March to start to plan how this will happen.” Her region includes just one comprehensive stroke center that already performs endovascular treatments for stroke, at the University of Cincinnati, which sits amid 16 other hospitals that perform acute stroke care and can administer TPA. “Ambulance-based triage will be a big issue,” she predicted.

Other aspects of improved triage will be training ambulance personal to better identify the more severe stroke patients who will most likely need endovascular treatment and improving communication between ambulance crews and receiving hospitals to further speed up a process that depends on quick treatment to get the best outcomes.

The ideal is “having paramedics call and tell us what is happening [in their ambulance] and give us as much information as possible so we can start planning for the patient’s arrival. Most hospitals don’t do this now; relatively few have their system well organized,” Dr. Goyal said in an interview. A finely orchestrated emergency transport system and hospital-based stroke team was part of the program developed at the University of Calgary by Dr. Goyal and his associates and which they credited with contributing to the successful embolectomy trial they led, called ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times)(N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905]). Dr. Goyal said that he is now visiting hospitals around the world to assist them in setting up stroke-response systems that mimic what was successful in Calgary and the other centers that participated in ESCAPE.

Improving triage with better screening

A key to improved ambulance triage will be identifying a simple, evidence-based method for assessing stroke severity that ambulance personnel can use to determine what sort of care a patient needs and where the patient needs to go to. Although a couple of U.S. sites have begun pilot studies of field-based CT units that allow stroke patients to undergo imaging-based assessment in the field, clinical evaluation remains the main tool used in the ambulance.

One possible tool is the Los Angeles Motor Scale (LAMS), a stroke-assessment scoring system developed by Dr. Saver and his associates for ambulance use about a decade ago (Prehosp. Emerg. Care 2004;8:46-50). “A LAMS score of 4 or 5 [on a scale of 0-5] is a good starting point, and with time it might improve,” Dr. Goyal said.

The National Institutes of Health Stroke Scale (NIHSS) is a clinical assessment tool not designed for prehospital use, but a new analysis reported at the meeting showed value in using the NIHSS to identify stroke patients who are good candidates for endovascular treatment, further suggesting that a simple screening tool could potentially work in the ambulance to identify patients who probably need embolectomy.

The new analysis combined data from two randomized trials: The IMS (Interventional Management of Stroke) III trial, the results of which, published in early 2013, showed no incremental benefit of endovascular therapy plus TPA over TPA alone for patients with acute ischemic stroke (N. Engl. J. Med. 2013;368:893-903); and the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) trial, the results of which, published in January, showed a significant incremental benefit from endovascular treatment – it was the first of the four studies recently reported to show this benefit (N. Engl. J. Med. 2015;372:11-20).

The combined data included all patients from both studies with a NIHSS score of at least 20, indicating a very severe stroke. This produced a total of 342 patients, of whom 191 received intravenous TPA plus endovascular treatment and 152 received only TPA. After 90 days, 24% of the patients treated with endovascular treatment and 14% of those treated only with TPA had a modified Rankin Scale score of 0-2, indicating no or limited disability, Dr. Joseph P. Broderick reported at the conference. After adjustments for age and other potential confounders, treatment with endovascular therapy produced a statistically significant 85% improvement in patients achieving an acceptable modified Rankin Scale score at 90 days, said Dr. Broderick, professor of neurology and director of the neuroscience institute at the University of Cincinnati.

“The NIHSS score is a surrogate for clot size. It is an imperfect measure, especially at lower levels, but when the score is 20 or higher it means the patient has a big clot” that will likely not fully respond to TPA but potentially will respond to embolectomy, Dr. Broderick said in an interview. “A patient with a NIHSS score of 20 or higher has about a 95% risk of having an ongoing major artery occlusion despite TPA treatment.”

“The challenge is that we don’t have a fully validated [prehospital] scoring system. Several groups are trying to create one; in the meantime we may come up with certain clinical thresholds” that can reliably guide ambulance crews on the best place to take each stroke patient, Dr. Khatri said.

Dr. Khatri has received research support from Penumbra and Genentech. Dr. Derdeyn has received honoraria from Penumbra and holds equity in Pulse Therapeutics. Dr. Saver has been a consultant to and received research support from Covidien. Dr. Adeoye has been a speaker for Genentech. Dr. Goldstein had no disclosures. Dr. Goyal has been a consultant to and received research support from Covidien and holds a patent on using CT angiography to diagnose stroke. Dr. Broderick has received research support from Genentech.

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler

NASHVILLE, TENN. – Results from three randomized controlled trials presented at the International Stroke Conference, plus the outcomes from a fourth trial first reported last fall, immediately established embolectomy as standard-of-care treatment for selected patients with acute ischemic stroke.

Stroke experts interviewed during the conference, however, said that making embolectomy routinely available to most U.S. stroke patients who would be candidates for the intervention will take months, if not years.

They envision challenges involving the availability of trained interventionalists, triage of patients to the right centers, and reimbursement issues as some of the obstacles to be dealt with before endovascular embolectomy aimed at removing intracerebral-artery occlusions in acute ischemic stroke patients becomes uniformly available.

Yet another challenge will arise when stroke-treatment groups that did not participate in the trials strive to replicate the success their colleagues reported by implementing the highly streamlined systems that were used in the trials for identifying appropriate stroke patients and for delivering treatment. Those systems were cited as an important reason why those studies succeeded in producing positive outcomes when similar embolectomy trials without the same efficiencies reported just a year or two ago failed to show benefit.

“The evidence makes it standard of care, but the challenge is that our systems are not set up. This is the big thing we will all go home to work on,” said Dr. Pooja Khatri, professor of neurology and director of acute stroke at the University of Cincinnati.

“You talk to everyone at this meeting, and what they want to go home and figure out is how can we deliver this care. It’s really challenging, at a myriad of levels,” said Dr. Colin P. Derdeyn, professor of neurology and director of the Center for Stroke and Cerebrovascular Disease at Washington University in St. Louis.

Growing endovascular availability

Arguably the most critical issue in rolling out endovascular stroke interventions more broadly is scaling up the number of centers that have the staff and systems in place to perform them. Clearly, the scope of providers able to deliver this treatment currently falls substantially short of what will be needed. “It’s kind of daunting to think about the [workforce] needs,” Dr. Khatri said in a talk at the conference, which was sponsored by the American Heart Association.

“In the United States, we’ve been building out a two-tier system, with comprehensive stroke centers capable of delivering this [endovascular embolectomy] treatment” and primary stroke centers capable of administering intravenous treatment with tissue plasminogen activator (TPA), the first treatment that patients eligible for embolectomy should receive, said Dr. Jeffrey L. Saver, professor of neurology and director of the stroke center at the University of California, Los Angeles, and lead investigator for one of the new embolectomy studies.

“Work groups have suggested about 60,000 U.S. stroke patients could potentially be treated with endovascular therapy, and we’d need about 300 comprehensive stroke centers to do this.” Dr. Saver estimated the current total of U.S. comprehensive stroke centers to be 75, a number that several others at the meeting pegged as more like 80, and they also noted that some centers are endovascular ready but have not received official comprehensive stroke center certification from the Joint Commission.

The extent to which availability of U.S. embolectomy remained limited through most of 2013 was apparent in data reported at the conference by Dr. Opeolu M. Adeoye, an emergency medicine physician and medical director of the telestroke program of the University of Cincinnati. During fiscal year 2013 (Oct. 2012 to Sept. 2013), 386,144 Medicare patients either older than 65 years or totally disabled had a primary hospital discharge diagnosis of stroke; of those, 5.1% had received thrombolytic therapy with intravenous TPA and 0.8% had undergone embolectomy. In a second analysis, he looked at stroke discharges and reperfusion treatments used in the 214 U.S. acute-care hospitals currently enrolled in StrokeNet, a program begun in 2013 by the National Institute of Neurological Disorders and Stroke to organize U.S. centers interested in participating in stroke trials.

During the same period, the 214 StrokeNet hospitals discharged 44,282 Medicare eligible patients who met the same age or disability criteria, with a TPA-treatment rate of 7.9% and an endovascular treatment rate of 2.2%. Although the StrokeNet hospitals treated roughly 11% of U.S. stroke patients in the specified demographic, they administered about 20% of the reperfusion treatment, Dr. Adeoye reported. He also highlighted that the 7.9% rate of TPA treatment among the StrokeNet hospitals correlated well with prior estimates that 6%-11% of stroke patients fulfill existing criteria for TPA treatment

A wide disparity existed in the rate of reperfusion use among StrokeNet hospitals. Sixty-seven hospitals, 31% of the StrokeNet group, treated at least 20 stroke patients with TPA during the study period, while 100 (47%) of the StrokeNet hospitals treated fewer than 10 acute stroke patients. The rate of those doing embolectomies was substantially lower, with 10 hospitals (5%) doing at least 20 endovascular procedures while 90% did fewer than 10.

Although Dr. Adeoye expressed confidence that the number of U.S. centers doing embolectomy cases will “change rapidly” following the new reports documenting the efficacy of the approach, he also acknowledged the challenges of growing the number of high-volume endovascular centers.

Centers that have been equivocal about embolectomy will now start doing it in a more concerted way, he predicted, but if cases get spread out and some sites do only a few patients a year, the quality of the procedures may suffer. “The more cases a site does, the better,” he noted, adding that regions that funnel all their stroke patients to a single endovascular site “do really well.”

“Right now, many hospitals want to do everything to get [fully] reimbursed and not send their patients down the line. There is a financial incentive to build up the stroke service at every hospital,” Dr. Derdeyn noted.

Another aspect to sorting out which centers start offering endovascular treatment will be the need to locate them in a rational way, as happened with trauma centers. Until now, placement of comprehensive stroke centers often depended on hospitals developing the capability as a marketing tool, noted Dr. Larry B. Goldstein, professor of neurology and director of the stroke center at Duke University in Durham, N.C. A hospital might achieve comprehensive stroke center certification, so a second center a few blocks away then follows suit seemingly to keep pace in a public-relations battle for cachet. The result has been an irrational clustering of centers with endovascular capability. He cited the situation in Cleveland, where comprehensive centers run by the Cleveland Clinic and Case Western stand a few dozen feet apart.

Challenges for triage

An analysis published last year by Dr. Adeoye and his colleagues showed that 56% of the U.S. population lived within a 60-minute drive of a hospital able to administer endovascular stroke treatment; by air, 85% had that access (Stroke 2014;45:3019-24). For TPA, 81% of people lived within a 60-minute drive of a center able to administer intravenous lytic treatment and 97% could reach these hospitals within an hour by air. While those numbers sound promising, though, fulfilling that potential depends on getting the right patients to the right hospitals.

Patient triage is perhaps the most vexing issue created by embolectomy’s success. For at least the short term, a limited number of centers will have the staffing and capacity to deliver endovascular embolectomy on a 24/7 basis to acute ischemic stroke patients who have a proximal blockage in a large cerebral artery. The relatively small number of sites able to offer embolectomy, and the much larger number of sites able to administer thrombolytic therapy with TPA, set the stage for some possible tension, or at least confusion, within communities over where an ambulance should bring an acute ischemic stroke patient.

“In some places they have trained the EMS [emergency medical services] to recognize severe strokes that are likely to benefit [from embolectomy], and they take those patients to places with endovascular capability. But there are some states with laws against doing this. There are major issues when EMS bypasses hospitals,” Dr. Derdeyn noted. “That’s the million-dollar question: How do you identify the stroke patients [with severe strokes who would benefit from embolectomy] and get them to where they need to go.” Like Dr. Adeoye, Dr. Derdeyn believes that endovascular treatment for stroke needs to be centralized at a relatively small number of high-volume centers.

“You can imagine that the fastest way to get stroke patients treated is to have them all go to one place, but that is much easier said than done,” Dr. Khatri said.

“Stent retrievers get cerebral arteries open, but that is not the biggest challenge. For the short term, the key issue is to get the correct patients to the correct hospitals where they can be treated by the correct team,” said Dr. Mayank Goyal, professor of diagnostic imaging at the University of Calgary (Alta.) and lead investigator for two of the three trials presented at the conference.

“You need a neurologist capable of deciding whether it really is a stroke, and pretty high-level imaging to identify the large-vessel occlusions that will benefit. Acquiring a CT angiography (CTA) image of the brain is a push-button process, but figuring out what the CTA says is not push button, especially the more sophisticated perfusion CT imaging to assess collateral circulation. I don’t see this capability happening in every catheterization laboratory,” Dr. Derdeyn said in an interview.

Another issue is volume. “Telemedicine may allow broader use of [more sophisticated] imaging, but if a place is only doing 20 endovascular procedures a year, they won’t have the best outcomes. Most small hospitals that today give patients TPA see 20 cases or fewer a year, and perhaps 5 patients will have a large-vessel occlusion,” Dr. Derdeyn said.

Before the new reports documenting the safety and efficacy of endovascular treatment, “we did not have the justification to bypass primary stroke centers and take patients directly to comprehensive stroke centers,” Dr. Khatri said. Now, “there is clear evidence that patients with severe strokes should not go to the nearby primary stroke center” but instead head directly for the centers capable of performing embolectomy. But Dr. Khatri also acknowledged that a complex calculation is needed to balance the trade off: Is it better to take a stroke patient more quickly to a nearby hospital that can only start TPA and perhaps later forward the patient to an embolectomy-ready hospital, or to transport the patient somewhat further to a facility able to deliver both TPA and embolectomy?

Dr. Khatri said that, in the Cincinnati area, “we have scheduled a retreat for March to start to plan how this will happen.” Her region includes just one comprehensive stroke center that already performs endovascular treatments for stroke, at the University of Cincinnati, which sits amid 16 other hospitals that perform acute stroke care and can administer TPA. “Ambulance-based triage will be a big issue,” she predicted.

Other aspects of improved triage will be training ambulance personal to better identify the more severe stroke patients who will most likely need endovascular treatment and improving communication between ambulance crews and receiving hospitals to further speed up a process that depends on quick treatment to get the best outcomes.

The ideal is “having paramedics call and tell us what is happening [in their ambulance] and give us as much information as possible so we can start planning for the patient’s arrival. Most hospitals don’t do this now; relatively few have their system well organized,” Dr. Goyal said in an interview. A finely orchestrated emergency transport system and hospital-based stroke team was part of the program developed at the University of Calgary by Dr. Goyal and his associates and which they credited with contributing to the successful embolectomy trial they led, called ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times)(N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905]). Dr. Goyal said that he is now visiting hospitals around the world to assist them in setting up stroke-response systems that mimic what was successful in Calgary and the other centers that participated in ESCAPE.

Improving triage with better screening

A key to improved ambulance triage will be identifying a simple, evidence-based method for assessing stroke severity that ambulance personnel can use to determine what sort of care a patient needs and where the patient needs to go to. Although a couple of U.S. sites have begun pilot studies of field-based CT units that allow stroke patients to undergo imaging-based assessment in the field, clinical evaluation remains the main tool used in the ambulance.

One possible tool is the Los Angeles Motor Scale (LAMS), a stroke-assessment scoring system developed by Dr. Saver and his associates for ambulance use about a decade ago (Prehosp. Emerg. Care 2004;8:46-50). “A LAMS score of 4 or 5 [on a scale of 0-5] is a good starting point, and with time it might improve,” Dr. Goyal said.

The National Institutes of Health Stroke Scale (NIHSS) is a clinical assessment tool not designed for prehospital use, but a new analysis reported at the meeting showed value in using the NIHSS to identify stroke patients who are good candidates for endovascular treatment, further suggesting that a simple screening tool could potentially work in the ambulance to identify patients who probably need embolectomy.

The new analysis combined data from two randomized trials: The IMS (Interventional Management of Stroke) III trial, the results of which, published in early 2013, showed no incremental benefit of endovascular therapy plus TPA over TPA alone for patients with acute ischemic stroke (N. Engl. J. Med. 2013;368:893-903); and the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) trial, the results of which, published in January, showed a significant incremental benefit from endovascular treatment – it was the first of the four studies recently reported to show this benefit (N. Engl. J. Med. 2015;372:11-20).

The combined data included all patients from both studies with a NIHSS score of at least 20, indicating a very severe stroke. This produced a total of 342 patients, of whom 191 received intravenous TPA plus endovascular treatment and 152 received only TPA. After 90 days, 24% of the patients treated with endovascular treatment and 14% of those treated only with TPA had a modified Rankin Scale score of 0-2, indicating no or limited disability, Dr. Joseph P. Broderick reported at the conference. After adjustments for age and other potential confounders, treatment with endovascular therapy produced a statistically significant 85% improvement in patients achieving an acceptable modified Rankin Scale score at 90 days, said Dr. Broderick, professor of neurology and director of the neuroscience institute at the University of Cincinnati.

“The NIHSS score is a surrogate for clot size. It is an imperfect measure, especially at lower levels, but when the score is 20 or higher it means the patient has a big clot” that will likely not fully respond to TPA but potentially will respond to embolectomy, Dr. Broderick said in an interview. “A patient with a NIHSS score of 20 or higher has about a 95% risk of having an ongoing major artery occlusion despite TPA treatment.”

“The challenge is that we don’t have a fully validated [prehospital] scoring system. Several groups are trying to create one; in the meantime we may come up with certain clinical thresholds” that can reliably guide ambulance crews on the best place to take each stroke patient, Dr. Khatri said.

Dr. Khatri has received research support from Penumbra and Genentech. Dr. Derdeyn has received honoraria from Penumbra and holds equity in Pulse Therapeutics. Dr. Saver has been a consultant to and received research support from Covidien. Dr. Adeoye has been a speaker for Genentech. Dr. Goldstein had no disclosures. Dr. Goyal has been a consultant to and received research support from Covidien and holds a patent on using CT angiography to diagnose stroke. Dr. Broderick has received research support from Genentech.

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler

NASHVILLE, TENN. – Results from three randomized controlled trials presented at the International Stroke Conference, plus the outcomes from a fourth trial first reported last fall, immediately established embolectomy as standard-of-care treatment for selected patients with acute ischemic stroke.

Stroke experts interviewed during the conference, however, said that making embolectomy routinely available to most U.S. stroke patients who would be candidates for the intervention will take months, if not years.

They envision challenges involving the availability of trained interventionalists, triage of patients to the right centers, and reimbursement issues as some of the obstacles to be dealt with before endovascular embolectomy aimed at removing intracerebral-artery occlusions in acute ischemic stroke patients becomes uniformly available.

Yet another challenge will arise when stroke-treatment groups that did not participate in the trials strive to replicate the success their colleagues reported by implementing the highly streamlined systems that were used in the trials for identifying appropriate stroke patients and for delivering treatment. Those systems were cited as an important reason why those studies succeeded in producing positive outcomes when similar embolectomy trials without the same efficiencies reported just a year or two ago failed to show benefit.

“The evidence makes it standard of care, but the challenge is that our systems are not set up. This is the big thing we will all go home to work on,” said Dr. Pooja Khatri, professor of neurology and director of acute stroke at the University of Cincinnati.

“You talk to everyone at this meeting, and what they want to go home and figure out is how can we deliver this care. It’s really challenging, at a myriad of levels,” said Dr. Colin P. Derdeyn, professor of neurology and director of the Center for Stroke and Cerebrovascular Disease at Washington University in St. Louis.

Growing endovascular availability

Arguably the most critical issue in rolling out endovascular stroke interventions more broadly is scaling up the number of centers that have the staff and systems in place to perform them. Clearly, the scope of providers able to deliver this treatment currently falls substantially short of what will be needed. “It’s kind of daunting to think about the [workforce] needs,” Dr. Khatri said in a talk at the conference, which was sponsored by the American Heart Association.

“In the United States, we’ve been building out a two-tier system, with comprehensive stroke centers capable of delivering this [endovascular embolectomy] treatment” and primary stroke centers capable of administering intravenous treatment with tissue plasminogen activator (TPA), the first treatment that patients eligible for embolectomy should receive, said Dr. Jeffrey L. Saver, professor of neurology and director of the stroke center at the University of California, Los Angeles, and lead investigator for one of the new embolectomy studies.

“Work groups have suggested about 60,000 U.S. stroke patients could potentially be treated with endovascular therapy, and we’d need about 300 comprehensive stroke centers to do this.” Dr. Saver estimated the current total of U.S. comprehensive stroke centers to be 75, a number that several others at the meeting pegged as more like 80, and they also noted that some centers are endovascular ready but have not received official comprehensive stroke center certification from the Joint Commission.

The extent to which availability of U.S. embolectomy remained limited through most of 2013 was apparent in data reported at the conference by Dr. Opeolu M. Adeoye, an emergency medicine physician and medical director of the telestroke program of the University of Cincinnati. During fiscal year 2013 (Oct. 2012 to Sept. 2013), 386,144 Medicare patients either older than 65 years or totally disabled had a primary hospital discharge diagnosis of stroke; of those, 5.1% had received thrombolytic therapy with intravenous TPA and 0.8% had undergone embolectomy. In a second analysis, he looked at stroke discharges and reperfusion treatments used in the 214 U.S. acute-care hospitals currently enrolled in StrokeNet, a program begun in 2013 by the National Institute of Neurological Disorders and Stroke to organize U.S. centers interested in participating in stroke trials.

During the same period, the 214 StrokeNet hospitals discharged 44,282 Medicare eligible patients who met the same age or disability criteria, with a TPA-treatment rate of 7.9% and an endovascular treatment rate of 2.2%. Although the StrokeNet hospitals treated roughly 11% of U.S. stroke patients in the specified demographic, they administered about 20% of the reperfusion treatment, Dr. Adeoye reported. He also highlighted that the 7.9% rate of TPA treatment among the StrokeNet hospitals correlated well with prior estimates that 6%-11% of stroke patients fulfill existing criteria for TPA treatment

A wide disparity existed in the rate of reperfusion use among StrokeNet hospitals. Sixty-seven hospitals, 31% of the StrokeNet group, treated at least 20 stroke patients with TPA during the study period, while 100 (47%) of the StrokeNet hospitals treated fewer than 10 acute stroke patients. The rate of those doing embolectomies was substantially lower, with 10 hospitals (5%) doing at least 20 endovascular procedures while 90% did fewer than 10.

Although Dr. Adeoye expressed confidence that the number of U.S. centers doing embolectomy cases will “change rapidly” following the new reports documenting the efficacy of the approach, he also acknowledged the challenges of growing the number of high-volume endovascular centers.

Centers that have been equivocal about embolectomy will now start doing it in a more concerted way, he predicted, but if cases get spread out and some sites do only a few patients a year, the quality of the procedures may suffer. “The more cases a site does, the better,” he noted, adding that regions that funnel all their stroke patients to a single endovascular site “do really well.”

“Right now, many hospitals want to do everything to get [fully] reimbursed and not send their patients down the line. There is a financial incentive to build up the stroke service at every hospital,” Dr. Derdeyn noted.

Another aspect to sorting out which centers start offering endovascular treatment will be the need to locate them in a rational way, as happened with trauma centers. Until now, placement of comprehensive stroke centers often depended on hospitals developing the capability as a marketing tool, noted Dr. Larry B. Goldstein, professor of neurology and director of the stroke center at Duke University in Durham, N.C. A hospital might achieve comprehensive stroke center certification, so a second center a few blocks away then follows suit seemingly to keep pace in a public-relations battle for cachet. The result has been an irrational clustering of centers with endovascular capability. He cited the situation in Cleveland, where comprehensive centers run by the Cleveland Clinic and Case Western stand a few dozen feet apart.

Challenges for triage

An analysis published last year by Dr. Adeoye and his colleagues showed that 56% of the U.S. population lived within a 60-minute drive of a hospital able to administer endovascular stroke treatment; by air, 85% had that access (Stroke 2014;45:3019-24). For TPA, 81% of people lived within a 60-minute drive of a center able to administer intravenous lytic treatment and 97% could reach these hospitals within an hour by air. While those numbers sound promising, though, fulfilling that potential depends on getting the right patients to the right hospitals.

Patient triage is perhaps the most vexing issue created by embolectomy’s success. For at least the short term, a limited number of centers will have the staffing and capacity to deliver endovascular embolectomy on a 24/7 basis to acute ischemic stroke patients who have a proximal blockage in a large cerebral artery. The relatively small number of sites able to offer embolectomy, and the much larger number of sites able to administer thrombolytic therapy with TPA, set the stage for some possible tension, or at least confusion, within communities over where an ambulance should bring an acute ischemic stroke patient.

“In some places they have trained the EMS [emergency medical services] to recognize severe strokes that are likely to benefit [from embolectomy], and they take those patients to places with endovascular capability. But there are some states with laws against doing this. There are major issues when EMS bypasses hospitals,” Dr. Derdeyn noted. “That’s the million-dollar question: How do you identify the stroke patients [with severe strokes who would benefit from embolectomy] and get them to where they need to go.” Like Dr. Adeoye, Dr. Derdeyn believes that endovascular treatment for stroke needs to be centralized at a relatively small number of high-volume centers.

“You can imagine that the fastest way to get stroke patients treated is to have them all go to one place, but that is much easier said than done,” Dr. Khatri said.

“Stent retrievers get cerebral arteries open, but that is not the biggest challenge. For the short term, the key issue is to get the correct patients to the correct hospitals where they can be treated by the correct team,” said Dr. Mayank Goyal, professor of diagnostic imaging at the University of Calgary (Alta.) and lead investigator for two of the three trials presented at the conference.

“You need a neurologist capable of deciding whether it really is a stroke, and pretty high-level imaging to identify the large-vessel occlusions that will benefit. Acquiring a CT angiography (CTA) image of the brain is a push-button process, but figuring out what the CTA says is not push button, especially the more sophisticated perfusion CT imaging to assess collateral circulation. I don’t see this capability happening in every catheterization laboratory,” Dr. Derdeyn said in an interview.

Another issue is volume. “Telemedicine may allow broader use of [more sophisticated] imaging, but if a place is only doing 20 endovascular procedures a year, they won’t have the best outcomes. Most small hospitals that today give patients TPA see 20 cases or fewer a year, and perhaps 5 patients will have a large-vessel occlusion,” Dr. Derdeyn said.

Before the new reports documenting the safety and efficacy of endovascular treatment, “we did not have the justification to bypass primary stroke centers and take patients directly to comprehensive stroke centers,” Dr. Khatri said. Now, “there is clear evidence that patients with severe strokes should not go to the nearby primary stroke center” but instead head directly for the centers capable of performing embolectomy. But Dr. Khatri also acknowledged that a complex calculation is needed to balance the trade off: Is it better to take a stroke patient more quickly to a nearby hospital that can only start TPA and perhaps later forward the patient to an embolectomy-ready hospital, or to transport the patient somewhat further to a facility able to deliver both TPA and embolectomy?

Dr. Khatri said that, in the Cincinnati area, “we have scheduled a retreat for March to start to plan how this will happen.” Her region includes just one comprehensive stroke center that already performs endovascular treatments for stroke, at the University of Cincinnati, which sits amid 16 other hospitals that perform acute stroke care and can administer TPA. “Ambulance-based triage will be a big issue,” she predicted.

Other aspects of improved triage will be training ambulance personal to better identify the more severe stroke patients who will most likely need endovascular treatment and improving communication between ambulance crews and receiving hospitals to further speed up a process that depends on quick treatment to get the best outcomes.

The ideal is “having paramedics call and tell us what is happening [in their ambulance] and give us as much information as possible so we can start planning for the patient’s arrival. Most hospitals don’t do this now; relatively few have their system well organized,” Dr. Goyal said in an interview. A finely orchestrated emergency transport system and hospital-based stroke team was part of the program developed at the University of Calgary by Dr. Goyal and his associates and which they credited with contributing to the successful embolectomy trial they led, called ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times)(N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905]). Dr. Goyal said that he is now visiting hospitals around the world to assist them in setting up stroke-response systems that mimic what was successful in Calgary and the other centers that participated in ESCAPE.

Improving triage with better screening

A key to improved ambulance triage will be identifying a simple, evidence-based method for assessing stroke severity that ambulance personnel can use to determine what sort of care a patient needs and where the patient needs to go to. Although a couple of U.S. sites have begun pilot studies of field-based CT units that allow stroke patients to undergo imaging-based assessment in the field, clinical evaluation remains the main tool used in the ambulance.

One possible tool is the Los Angeles Motor Scale (LAMS), a stroke-assessment scoring system developed by Dr. Saver and his associates for ambulance use about a decade ago (Prehosp. Emerg. Care 2004;8:46-50). “A LAMS score of 4 or 5 [on a scale of 0-5] is a good starting point, and with time it might improve,” Dr. Goyal said.

The National Institutes of Health Stroke Scale (NIHSS) is a clinical assessment tool not designed for prehospital use, but a new analysis reported at the meeting showed value in using the NIHSS to identify stroke patients who are good candidates for endovascular treatment, further suggesting that a simple screening tool could potentially work in the ambulance to identify patients who probably need embolectomy.

The new analysis combined data from two randomized trials: The IMS (Interventional Management of Stroke) III trial, the results of which, published in early 2013, showed no incremental benefit of endovascular therapy plus TPA over TPA alone for patients with acute ischemic stroke (N. Engl. J. Med. 2013;368:893-903); and the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) trial, the results of which, published in January, showed a significant incremental benefit from endovascular treatment – it was the first of the four studies recently reported to show this benefit (N. Engl. J. Med. 2015;372:11-20).

The combined data included all patients from both studies with a NIHSS score of at least 20, indicating a very severe stroke. This produced a total of 342 patients, of whom 191 received intravenous TPA plus endovascular treatment and 152 received only TPA. After 90 days, 24% of the patients treated with endovascular treatment and 14% of those treated only with TPA had a modified Rankin Scale score of 0-2, indicating no or limited disability, Dr. Joseph P. Broderick reported at the conference. After adjustments for age and other potential confounders, treatment with endovascular therapy produced a statistically significant 85% improvement in patients achieving an acceptable modified Rankin Scale score at 90 days, said Dr. Broderick, professor of neurology and director of the neuroscience institute at the University of Cincinnati.

“The NIHSS score is a surrogate for clot size. It is an imperfect measure, especially at lower levels, but when the score is 20 or higher it means the patient has a big clot” that will likely not fully respond to TPA but potentially will respond to embolectomy, Dr. Broderick said in an interview. “A patient with a NIHSS score of 20 or higher has about a 95% risk of having an ongoing major artery occlusion despite TPA treatment.”

“The challenge is that we don’t have a fully validated [prehospital] scoring system. Several groups are trying to create one; in the meantime we may come up with certain clinical thresholds” that can reliably guide ambulance crews on the best place to take each stroke patient, Dr. Khatri said.

Dr. Khatri has received research support from Penumbra and Genentech. Dr. Derdeyn has received honoraria from Penumbra and holds equity in Pulse Therapeutics. Dr. Saver has been a consultant to and received research support from Covidien. Dr. Adeoye has been a speaker for Genentech. Dr. Goldstein had no disclosures. Dr. Goyal has been a consultant to and received research support from Covidien and holds a patent on using CT angiography to diagnose stroke. Dr. Broderick has received research support from Genentech.

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler

NASHVILLE, TENN. – U.S. stroke specialists now face the challenge of making endovascular embolectomy a routinely available option for selected patients with acute ischemic stroke, Dr. Pooja Khatri said in an interview at the International Stroke Conference.

During the conference, which was sponsored by the American Heart Association, new reports from three independent, randomized controlled trials, as well as data from a fourth study published in January, collectively established endovascular embolectomy as the new standard-of-care treatment for acute ischemic stroke patients with a proximal occlusion of a large, intracerebral artery. The stroke community, however, now faces the responsibility of figuring out how to make this a reality.

Among the hurdles they face are using CT imaging or other methods to identify in daily practice the specific patients who will get the biggest benefit from endovascular treatment and finding a consensus within each region on how to triage acute stroke patients to centers that can perform embolectomy, said Dr. Khatri, professor of neurology and director of acute stroke at the University of Cincinnati. In Cincinnati, Dr. Khatri and her colleagues are planning to soon hold a retreat with representatives from other area hospitals to try to work out the logistics.Dr. Khatri has received research support from Penumbra and Genentech.

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler

NASHVILLE, TENN. – U.S. stroke specialists now face the challenge of making endovascular embolectomy a routinely available option for selected patients with acute ischemic stroke, Dr. Pooja Khatri said in an interview at the International Stroke Conference.

During the conference, which was sponsored by the American Heart Association, new reports from three independent, randomized controlled trials, as well as data from a fourth study published in January, collectively established endovascular embolectomy as the new standard-of-care treatment for acute ischemic stroke patients with a proximal occlusion of a large, intracerebral artery. The stroke community, however, now faces the responsibility of figuring out how to make this a reality.

Among the hurdles they face are using CT imaging or other methods to identify in daily practice the specific patients who will get the biggest benefit from endovascular treatment and finding a consensus within each region on how to triage acute stroke patients to centers that can perform embolectomy, said Dr. Khatri, professor of neurology and director of acute stroke at the University of Cincinnati. In Cincinnati, Dr. Khatri and her colleagues are planning to soon hold a retreat with representatives from other area hospitals to try to work out the logistics.Dr. Khatri has received research support from Penumbra and Genentech.

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler

NASHVILLE, TENN. – U.S. stroke specialists now face the challenge of making endovascular embolectomy a routinely available option for selected patients with acute ischemic stroke, Dr. Pooja Khatri said in an interview at the International Stroke Conference.

During the conference, which was sponsored by the American Heart Association, new reports from three independent, randomized controlled trials, as well as data from a fourth study published in January, collectively established endovascular embolectomy as the new standard-of-care treatment for acute ischemic stroke patients with a proximal occlusion of a large, intracerebral artery. The stroke community, however, now faces the responsibility of figuring out how to make this a reality.

Among the hurdles they face are using CT imaging or other methods to identify in daily practice the specific patients who will get the biggest benefit from endovascular treatment and finding a consensus within each region on how to triage acute stroke patients to centers that can perform embolectomy, said Dr. Khatri, professor of neurology and director of acute stroke at the University of Cincinnati. In Cincinnati, Dr. Khatri and her colleagues are planning to soon hold a retreat with representatives from other area hospitals to try to work out the logistics.Dr. Khatri has received research support from Penumbra and Genentech.

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler

NASHVILLE, TENN. – The 10-year outcome for most giant intracranial aneurysms is rather dismal even if the lesions are initially successfully treated, according to findings from the International Study of Unruptured Intracranial Aneurysms.

Most patients lived through the first 2 years after diagnosis, but by 10 years, 37% of treated patients had died. Untreated patients had significantly higher mortality at 57%, Dr. James C. Torner said at the International Stroke Conference, which was sponsored by the American Heart Association.

“Compared to small aneurysms, the risk of all-cause mortality for these giant aneurysms is seven times greater in the first year, and the risk of hemorrhage or procedure-related death is 15 times higher. The risk does decrease over time, but it’s still elevated. It’s twice as high for death from hemorrhage and six times more likely from death due to rupture or a procedure by 10 years.”

Dr. Torner of the University of Iowa, Iowa City, presented 10-year outcomes from the International Study of Unruptured Intracranial Aneurysms (ISUIA), which followed 4,059 patients, of whom 187 had a giant unruptured intracranial aneurysm.

The mean lesion size was about 30 mm, but ranged from 25 to 63 mm. A third involved the internal carotid, and another third were cavernous. The remainder were either vestibular, posterior communicating, anterior cerebral, or middle cerebral.

Most were irregular; about 40% were a single sac. Daughter sacs were present in the rest. The volume ranged from 1,100 to 38,000 mm³, with about 10% having a volume of greater than 20,000 mm³.

Most of the patients were women (91%). Age was not related to occurrence; patients ranged from 25 to 82 years. There were some common risk factors, including smoking (in 70%), a family history of aneurysm (in 10%), a family history of coronary artery disease (in up to 45%, depending on patient age), hypertension (in up to 40%), and vascular headache. Patients aged 50 years or older were most likely to present with vascular headache (75%).

The baseline score on the modified Rankin Scale (mRS) was 1 in about 93% of the group. But 80% presented with some symptoms, including cranial nerve deficit (47%; commonly in cranial nerves III and IV), mass effect (16%), headache (44%), orbital pain (21%), and partial vision loss (25%).

Surgery was performed in 39% and endovascular treatment in 27%; the rest of the patients were initially untreated, although 3% later received endovascular treatment and 5% underwent surgical treatment during the follow-up period.

By 10 years, many of the lesions had ruptured. Posterior aneurysms were most likely to rupture (53%), while cavernous aneurysms were least likely to rupture (5%). About a third of the posterior communicating and 36% of the anterior lesions were unruptured.

The risk of rupture increased over the first 5 years, rising from almost 0% in year 1 to 20% by year 5. “Hemorrhage risk is huge over the first 5 years, even with the cavernous aneurysms – even they can rupture,” Dr. Torner said. “In those with smaller aneurysms, the risk of rupture may be high in the first 2 years, but then it subsides somewhat.”

Among the 59% of the overall group who survived, the mRS score remained excellent (1 or 2) by 10 years. Of the remainder who died, 23% died of a cranial or subarachnoid hemorrhage, and 11% of a cerebral infarct. Coronary disease, respiratory disease, and cancer were the other causes.

Treated patients generally fared better than untreated, although mortality varied significantly by lesion location. For anterior lesions, the death rate was 25% in untreated patients , 32% for surgical patients, and 19% in endovascular patients. Death rates for those with posterior communicating lesions were 90% for untreated and 50% for surgically treated patients; all of those with endovascular treatment died. For those with posterior lesions, death rates approached 100% for all groups.

Dr. Torner cautioned that because the study outcomes were collected during the 1990s, most treated patients underwent only coiling or clipping; better outcomes may be seen with more advanced therapies.

He said he had no relevant financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NASHVILLE, TENN. – The 10-year outcome for most giant intracranial aneurysms is rather dismal even if the lesions are initially successfully treated, according to findings from the International Study of Unruptured Intracranial Aneurysms.

Most patients lived through the first 2 years after diagnosis, but by 10 years, 37% of treated patients had died. Untreated patients had significantly higher mortality at 57%, Dr. James C. Torner said at the International Stroke Conference, which was sponsored by the American Heart Association.

“Compared to small aneurysms, the risk of all-cause mortality for these giant aneurysms is seven times greater in the first year, and the risk of hemorrhage or procedure-related death is 15 times higher. The risk does decrease over time, but it’s still elevated. It’s twice as high for death from hemorrhage and six times more likely from death due to rupture or a procedure by 10 years.”

Dr. Torner of the University of Iowa, Iowa City, presented 10-year outcomes from the International Study of Unruptured Intracranial Aneurysms (ISUIA), which followed 4,059 patients, of whom 187 had a giant unruptured intracranial aneurysm.

The mean lesion size was about 30 mm, but ranged from 25 to 63 mm. A third involved the internal carotid, and another third were cavernous. The remainder were either vestibular, posterior communicating, anterior cerebral, or middle cerebral.

Most were irregular; about 40% were a single sac. Daughter sacs were present in the rest. The volume ranged from 1,100 to 38,000 mm³, with about 10% having a volume of greater than 20,000 mm³.

Most of the patients were women (91%). Age was not related to occurrence; patients ranged from 25 to 82 years. There were some common risk factors, including smoking (in 70%), a family history of aneurysm (in 10%), a family history of coronary artery disease (in up to 45%, depending on patient age), hypertension (in up to 40%), and vascular headache. Patients aged 50 years or older were most likely to present with vascular headache (75%).

The baseline score on the modified Rankin Scale (mRS) was 1 in about 93% of the group. But 80% presented with some symptoms, including cranial nerve deficit (47%; commonly in cranial nerves III and IV), mass effect (16%), headache (44%), orbital pain (21%), and partial vision loss (25%).

Surgery was performed in 39% and endovascular treatment in 27%; the rest of the patients were initially untreated, although 3% later received endovascular treatment and 5% underwent surgical treatment during the follow-up period.

By 10 years, many of the lesions had ruptured. Posterior aneurysms were most likely to rupture (53%), while cavernous aneurysms were least likely to rupture (5%). About a third of the posterior communicating and 36% of the anterior lesions were unruptured.

The risk of rupture increased over the first 5 years, rising from almost 0% in year 1 to 20% by year 5. “Hemorrhage risk is huge over the first 5 years, even with the cavernous aneurysms – even they can rupture,” Dr. Torner said. “In those with smaller aneurysms, the risk of rupture may be high in the first 2 years, but then it subsides somewhat.”

Among the 59% of the overall group who survived, the mRS score remained excellent (1 or 2) by 10 years. Of the remainder who died, 23% died of a cranial or subarachnoid hemorrhage, and 11% of a cerebral infarct. Coronary disease, respiratory disease, and cancer were the other causes.

Treated patients generally fared better than untreated, although mortality varied significantly by lesion location. For anterior lesions, the death rate was 25% in untreated patients , 32% for surgical patients, and 19% in endovascular patients. Death rates for those with posterior communicating lesions were 90% for untreated and 50% for surgically treated patients; all of those with endovascular treatment died. For those with posterior lesions, death rates approached 100% for all groups.

Dr. Torner cautioned that because the study outcomes were collected during the 1990s, most treated patients underwent only coiling or clipping; better outcomes may be seen with more advanced therapies.

He said he had no relevant financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NASHVILLE, TENN. – The 10-year outcome for most giant intracranial aneurysms is rather dismal even if the lesions are initially successfully treated, according to findings from the International Study of Unruptured Intracranial Aneurysms.

Most patients lived through the first 2 years after diagnosis, but by 10 years, 37% of treated patients had died. Untreated patients had significantly higher mortality at 57%, Dr. James C. Torner said at the International Stroke Conference, which was sponsored by the American Heart Association.

“Compared to small aneurysms, the risk of all-cause mortality for these giant aneurysms is seven times greater in the first year, and the risk of hemorrhage or procedure-related death is 15 times higher. The risk does decrease over time, but it’s still elevated. It’s twice as high for death from hemorrhage and six times more likely from death due to rupture or a procedure by 10 years.”

Dr. Torner of the University of Iowa, Iowa City, presented 10-year outcomes from the International Study of Unruptured Intracranial Aneurysms (ISUIA), which followed 4,059 patients, of whom 187 had a giant unruptured intracranial aneurysm.

The mean lesion size was about 30 mm, but ranged from 25 to 63 mm. A third involved the internal carotid, and another third were cavernous. The remainder were either vestibular, posterior communicating, anterior cerebral, or middle cerebral.

Most were irregular; about 40% were a single sac. Daughter sacs were present in the rest. The volume ranged from 1,100 to 38,000 mm³, with about 10% having a volume of greater than 20,000 mm³.

Most of the patients were women (91%). Age was not related to occurrence; patients ranged from 25 to 82 years. There were some common risk factors, including smoking (in 70%), a family history of aneurysm (in 10%), a family history of coronary artery disease (in up to 45%, depending on patient age), hypertension (in up to 40%), and vascular headache. Patients aged 50 years or older were most likely to present with vascular headache (75%).

The baseline score on the modified Rankin Scale (mRS) was 1 in about 93% of the group. But 80% presented with some symptoms, including cranial nerve deficit (47%; commonly in cranial nerves III and IV), mass effect (16%), headache (44%), orbital pain (21%), and partial vision loss (25%).

Surgery was performed in 39% and endovascular treatment in 27%; the rest of the patients were initially untreated, although 3% later received endovascular treatment and 5% underwent surgical treatment during the follow-up period.

By 10 years, many of the lesions had ruptured. Posterior aneurysms were most likely to rupture (53%), while cavernous aneurysms were least likely to rupture (5%). About a third of the posterior communicating and 36% of the anterior lesions were unruptured.

The risk of rupture increased over the first 5 years, rising from almost 0% in year 1 to 20% by year 5. “Hemorrhage risk is huge over the first 5 years, even with the cavernous aneurysms – even they can rupture,” Dr. Torner said. “In those with smaller aneurysms, the risk of rupture may be high in the first 2 years, but then it subsides somewhat.”

Among the 59% of the overall group who survived, the mRS score remained excellent (1 or 2) by 10 years. Of the remainder who died, 23% died of a cranial or subarachnoid hemorrhage, and 11% of a cerebral infarct. Coronary disease, respiratory disease, and cancer were the other causes.

Treated patients generally fared better than untreated, although mortality varied significantly by lesion location. For anterior lesions, the death rate was 25% in untreated patients , 32% for surgical patients, and 19% in endovascular patients. Death rates for those with posterior communicating lesions were 90% for untreated and 50% for surgically treated patients; all of those with endovascular treatment died. For those with posterior lesions, death rates approached 100% for all groups.

Dr. Torner cautioned that because the study outcomes were collected during the 1990s, most treated patients underwent only coiling or clipping; better outcomes may be seen with more advanced therapies.

He said he had no relevant financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NASHVILLE, TENN. – The risk of a peripartum thrombotic event is rare, but significantly increased for women who have a cardioseptal defect. In a large national sample, the rate of thrombotic events was seven times higher among women with an atrial or ventral septal defect.

Advanced maternal age also was a significant independent predictor of this complication; among more than 7,000 women who developed a thrombotic complication, 81% were older than 45 years.

Dr. Ali Razmara of the University of Southern California, Los Angeles, mined the National Inpatient Sample for data linking peripartum thrombotic events to patient demographics and medical comorbidities. His cohort comprised 4.3 million normal vaginal and cesarean deliveries from 2000 to 2010. Events of interest included transient ischemic attack, ischemic stroke, hemorrhagic stroke, acute MI, and venous thromboembolism.

There were 7,242 peripartum thrombotic events (0.17%).The majority occurred in women who were older than 45 years (81%); white (58%); and admitted through the emergency department (67%). Women with thrombotic events were more likely to have hypertension (52% vs. 2%), dyslipidemia (26% vs. 0.52%), diabetes (20% vs. 2%), atrial fibrillation (10% vs. 0.23%), and heart failure (10% vs. 0.26%), he said at the International Stroke Conference.

A multivariate regression model controlled for patient demographics and comorbidities, including, among others, preeclampsia, hypercoagulable states, chorioamnionitis, renal and liver disease, hypertension, diabetes, and cardiovascular disorders including atrial fibrillation, heart failure, and atrial/ventral septal defects.

In a multivariate regression analysis, maternal age shook out as the most powerful independent risk factor; the rate of thrombosis was 91 times greater among women older than age 45 years.

Other significant independent predictors included emergency vs. routine admission (RR 3.3), cardiac septal defect (RR 7), preeclampsia (RR 3.3), and hypercoagulability (RR 3).

Dyslipidemia and hypertension doubled the rate of a thrombotic event. Hypertension, migraine, renal disease, heart disease, atrial fibrillation, and heart failure were also significant factors, increasing the rate of thrombosis by 40%-50%, Dr. Razmara said at the meeting, which was sponsored by the American Heart Association.

“Our goal is development of targeted interventions for screening, prevention, and treatment of thrombosis related to pregnancy.”

Dr. Razmara had no relevant financial disclosures.

msullivan@frontlinemedcom.com

NASHVILLE, TENN. – The risk of a peripartum thrombotic event is rare, but significantly increased for women who have a cardioseptal defect. In a large national sample, the rate of thrombotic events was seven times higher among women with an atrial or ventral septal defect.

Advanced maternal age also was a significant independent predictor of this complication; among more than 7,000 women who developed a thrombotic complication, 81% were older than 45 years.

Dr. Ali Razmara of the University of Southern California, Los Angeles, mined the National Inpatient Sample for data linking peripartum thrombotic events to patient demographics and medical comorbidities. His cohort comprised 4.3 million normal vaginal and cesarean deliveries from 2000 to 2010. Events of interest included transient ischemic attack, ischemic stroke, hemorrhagic stroke, acute MI, and venous thromboembolism.

There were 7,242 peripartum thrombotic events (0.17%).The majority occurred in women who were older than 45 years (81%); white (58%); and admitted through the emergency department (67%). Women with thrombotic events were more likely to have hypertension (52% vs. 2%), dyslipidemia (26% vs. 0.52%), diabetes (20% vs. 2%), atrial fibrillation (10% vs. 0.23%), and heart failure (10% vs. 0.26%), he said at the International Stroke Conference.

A multivariate regression model controlled for patient demographics and comorbidities, including, among others, preeclampsia, hypercoagulable states, chorioamnionitis, renal and liver disease, hypertension, diabetes, and cardiovascular disorders including atrial fibrillation, heart failure, and atrial/ventral septal defects.

In a multivariate regression analysis, maternal age shook out as the most powerful independent risk factor; the rate of thrombosis was 91 times greater among women older than age 45 years.

Other significant independent predictors included emergency vs. routine admission (RR 3.3), cardiac septal defect (RR 7), preeclampsia (RR 3.3), and hypercoagulability (RR 3).

Dyslipidemia and hypertension doubled the rate of a thrombotic event. Hypertension, migraine, renal disease, heart disease, atrial fibrillation, and heart failure were also significant factors, increasing the rate of thrombosis by 40%-50%, Dr. Razmara said at the meeting, which was sponsored by the American Heart Association.

“Our goal is development of targeted interventions for screening, prevention, and treatment of thrombosis related to pregnancy.”

Dr. Razmara had no relevant financial disclosures.

msullivan@frontlinemedcom.com

NASHVILLE, TENN. – The risk of a peripartum thrombotic event is rare, but significantly increased for women who have a cardioseptal defect. In a large national sample, the rate of thrombotic events was seven times higher among women with an atrial or ventral septal defect.

Advanced maternal age also was a significant independent predictor of this complication; among more than 7,000 women who developed a thrombotic complication, 81% were older than 45 years.

Dr. Ali Razmara of the University of Southern California, Los Angeles, mined the National Inpatient Sample for data linking peripartum thrombotic events to patient demographics and medical comorbidities. His cohort comprised 4.3 million normal vaginal and cesarean deliveries from 2000 to 2010. Events of interest included transient ischemic attack, ischemic stroke, hemorrhagic stroke, acute MI, and venous thromboembolism.

There were 7,242 peripartum thrombotic events (0.17%).The majority occurred in women who were older than 45 years (81%); white (58%); and admitted through the emergency department (67%). Women with thrombotic events were more likely to have hypertension (52% vs. 2%), dyslipidemia (26% vs. 0.52%), diabetes (20% vs. 2%), atrial fibrillation (10% vs. 0.23%), and heart failure (10% vs. 0.26%), he said at the International Stroke Conference.

A multivariate regression model controlled for patient demographics and comorbidities, including, among others, preeclampsia, hypercoagulable states, chorioamnionitis, renal and liver disease, hypertension, diabetes, and cardiovascular disorders including atrial fibrillation, heart failure, and atrial/ventral septal defects.

In a multivariate regression analysis, maternal age shook out as the most powerful independent risk factor; the rate of thrombosis was 91 times greater among women older than age 45 years.

Other significant independent predictors included emergency vs. routine admission (RR 3.3), cardiac septal defect (RR 7), preeclampsia (RR 3.3), and hypercoagulability (RR 3).

Dyslipidemia and hypertension doubled the rate of a thrombotic event. Hypertension, migraine, renal disease, heart disease, atrial fibrillation, and heart failure were also significant factors, increasing the rate of thrombosis by 40%-50%, Dr. Razmara said at the meeting, which was sponsored by the American Heart Association.

“Our goal is development of targeted interventions for screening, prevention, and treatment of thrombosis related to pregnancy.”

Dr. Razmara had no relevant financial disclosures.

msullivan@frontlinemedcom.com

NASHVILLE, TENN. – A 1 million–patient analysis of the Get With the Guidelines database found striking improvements in outcomes after ischemic stroke.

Despite the proven benefits of new-generation clot-retrieval devices, however, only about 2% of such stroke patients undergo endovascular therapy.

In a video interview at the International Stroke Conference, Dr. Bijoy Menon of the department of clinical neurosciences at the University of Calgary (Alta.), who presented the findings at the conference, discussed this apparent clinical paradox.

Dr. Menon’s study echoes findings of the landmark Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial, which found dramatically improved stroke outcomes after endovascular therapy.

But the benefits of such treatment should never outweigh the need for thoroughly screening patients and carefully considering their recovery prospects, Dr. Michael Hill, professor of neurology at the University of Calgary and primary investigator on the ESCAPE study, cautioned in another video interview at the meeting.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NASHVILLE, TENN. – A 1 million–patient analysis of the Get With the Guidelines database found striking improvements in outcomes after ischemic stroke.

Despite the proven benefits of new-generation clot-retrieval devices, however, only about 2% of such stroke patients undergo endovascular therapy.

In a video interview at the International Stroke Conference, Dr. Bijoy Menon of the department of clinical neurosciences at the University of Calgary (Alta.), who presented the findings at the conference, discussed this apparent clinical paradox.

Dr. Menon’s study echoes findings of the landmark Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial, which found dramatically improved stroke outcomes after endovascular therapy.

But the benefits of such treatment should never outweigh the need for thoroughly screening patients and carefully considering their recovery prospects, Dr. Michael Hill, professor of neurology at the University of Calgary and primary investigator on the ESCAPE study, cautioned in another video interview at the meeting.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NASHVILLE, TENN. – A 1 million–patient analysis of the Get With the Guidelines database found striking improvements in outcomes after ischemic stroke.

Despite the proven benefits of new-generation clot-retrieval devices, however, only about 2% of such stroke patients undergo endovascular therapy.

In a video interview at the International Stroke Conference, Dr. Bijoy Menon of the department of clinical neurosciences at the University of Calgary (Alta.), who presented the findings at the conference, discussed this apparent clinical paradox.

Dr. Menon’s study echoes findings of the landmark Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial, which found dramatically improved stroke outcomes after endovascular therapy.

But the benefits of such treatment should never outweigh the need for thoroughly screening patients and carefully considering their recovery prospects, Dr. Michael Hill, professor of neurology at the University of Calgary and primary investigator on the ESCAPE study, cautioned in another video interview at the meeting.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NASHVILLE, TENN. – Newly reported results from three trials showing “profound” benefit from endovascular embolectomy in selected patients with acute ischemic stroke “will have a major impact on how we treat stroke patients,” Dr. Lee H. Schwamm said during an interview at the International Stroke Conference.

“Many centers already provide this treatment, but this is the first time we have data on which patients to select” for catheter-based embolectomy, said Dr. Schwamm, professor of neurology at Harvard Medical School and director of acute stroke services at Massachusetts General Hospital in Boston. “Because we already have the capability in many centers, the first focus will be to extend the number of centers that can do this,” Dr. Schwamm noted.

An important part of that will be “changing the public health system to route patients to appropriate facilities” that can perform embolectomy, he said at the conference, sponsored by the American Heart Association.

Dr. Schwamm also noted that intravenous, thrombolytic treatment with tissue plasminogen activator (TPA) remains unchanged as the key first treatment for all patients with acute ischemic stroke. Following that, selected patients who do not fully respond to TPA should proceed to embolectomy. However, the new findings “do not suggest that you should avoid TPA and go directly to the catheter,” Dr. Schwamm cautioned.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NASHVILLE, TENN. – Newly reported results from three trials showing “profound” benefit from endovascular embolectomy in selected patients with acute ischemic stroke “will have a major impact on how we treat stroke patients,” Dr. Lee H. Schwamm said during an interview at the International Stroke Conference.

“Many centers already provide this treatment, but this is the first time we have data on which patients to select” for catheter-based embolectomy, said Dr. Schwamm, professor of neurology at Harvard Medical School and director of acute stroke services at Massachusetts General Hospital in Boston. “Because we already have the capability in many centers, the first focus will be to extend the number of centers that can do this,” Dr. Schwamm noted.

An important part of that will be “changing the public health system to route patients to appropriate facilities” that can perform embolectomy, he said at the conference, sponsored by the American Heart Association.

Dr. Schwamm also noted that intravenous, thrombolytic treatment with tissue plasminogen activator (TPA) remains unchanged as the key first treatment for all patients with acute ischemic stroke. Following that, selected patients who do not fully respond to TPA should proceed to embolectomy. However, the new findings “do not suggest that you should avoid TPA and go directly to the catheter,” Dr. Schwamm cautioned.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NASHVILLE, TENN. – Newly reported results from three trials showing “profound” benefit from endovascular embolectomy in selected patients with acute ischemic stroke “will have a major impact on how we treat stroke patients,” Dr. Lee H. Schwamm said during an interview at the International Stroke Conference.

“Many centers already provide this treatment, but this is the first time we have data on which patients to select” for catheter-based embolectomy, said Dr. Schwamm, professor of neurology at Harvard Medical School and director of acute stroke services at Massachusetts General Hospital in Boston. “Because we already have the capability in many centers, the first focus will be to extend the number of centers that can do this,” Dr. Schwamm noted.

An important part of that will be “changing the public health system to route patients to appropriate facilities” that can perform embolectomy, he said at the conference, sponsored by the American Heart Association.

Dr. Schwamm also noted that intravenous, thrombolytic treatment with tissue plasminogen activator (TPA) remains unchanged as the key first treatment for all patients with acute ischemic stroke. Following that, selected patients who do not fully respond to TPA should proceed to embolectomy. However, the new findings “do not suggest that you should avoid TPA and go directly to the catheter,” Dr. Schwamm cautioned.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NASHVILLE, TENN. – Last year, the Eighth Joint National Committee revised upward its classification of hypertension in healthy adults aged 60 years and older, recommending treatment when systolic pressure hits at least 150 mm Hg, or diastolic pressure reaches at least 90 mm Hg.

But raising the treatment cut point by 10 mm Hg from the earlier JNC 7 recommendations is a bad idea, Dr. Ralph L. Sacco warned at the International Stroke Conference – very bad, in fact.

And Dr. Sacco, the Olemberg Family Chair in Neurological Disorders at the University of Miami, said he has the data to prove it.

In a video interview at the meeting, Dr. Sacco outlined the findings from a new study exploring the stroke risks of patients who might find themselves now deemed normotensive under the JNC 8 hypertension guidelines.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NASHVILLE, TENN. – Last year, the Eighth Joint National Committee revised upward its classification of hypertension in healthy adults aged 60 years and older, recommending treatment when systolic pressure hits at least 150 mm Hg, or diastolic pressure reaches at least 90 mm Hg.

But raising the treatment cut point by 10 mm Hg from the earlier JNC 7 recommendations is a bad idea, Dr. Ralph L. Sacco warned at the International Stroke Conference – very bad, in fact.

And Dr. Sacco, the Olemberg Family Chair in Neurological Disorders at the University of Miami, said he has the data to prove it.

In a video interview at the meeting, Dr. Sacco outlined the findings from a new study exploring the stroke risks of patients who might find themselves now deemed normotensive under the JNC 8 hypertension guidelines.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NASHVILLE, TENN. – Last year, the Eighth Joint National Committee revised upward its classification of hypertension in healthy adults aged 60 years and older, recommending treatment when systolic pressure hits at least 150 mm Hg, or diastolic pressure reaches at least 90 mm Hg.

But raising the treatment cut point by 10 mm Hg from the earlier JNC 7 recommendations is a bad idea, Dr. Ralph L. Sacco warned at the International Stroke Conference – very bad, in fact.

And Dr. Sacco, the Olemberg Family Chair in Neurological Disorders at the University of Miami, said he has the data to prove it.

In a video interview at the meeting, Dr. Sacco outlined the findings from a new study exploring the stroke risks of patients who might find themselves now deemed normotensive under the JNC 8 hypertension guidelines.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NASHVILLE, TENN. – Treatment of selected patients with acute ischemic stroke underwent a dramatic, sudden shift with reports from three randomized, controlled trials that showed substantial added benefit and no incremental risk with the use of catheter-based embolic retrieval to open blocked intracerebral arteries when performed on top of standard thrombolytic therapy.

The three studies, each run independently and based in different countries, supported the results first reported last October and published online in December (N. Engl. J. Med. 2015;372:11-20) from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) study. These were the first contemporary trial results to show a jump in functional outcomes with use of a stent retriever catheter to pluck out the occluding embolus from an artery in the stroke patient’s brain to restore normal blood flow.

All three of the newly-reported studies stopped before reaching their prespecified enrollment levels because of overwhelming evidence for embolectomy’s incremental efficacy.

With four reports from prospective, randomized trials showing similar benefits and no added harm to patients, experts at the International Stroke Conference uniformly anointed catheter-based embolectomy the new standard of care for the small percentage of acute, ischemic-stroke patients who present with proximal, large-artery obstructions and also match the other strict clinical and imaging inclusion and exclusion criteria used in the studies.

Mitchel L. Zoler/Frontline Medical News

“Starting now, in patients with an acute ischemic stroke due to proximal vessel occlusion, rapid endovascular treatment using a retrieval stent is the standard of care,” Dr. Mayank Goyal declared from the plenary-session podium. He is a professor of diagnostic imaging at the University of Calgary (Canada) and an investigator in two of the three trials presented at the conference, which was sponsored by the American Heart Association.

“Today the world changed. We are now in a new era, the era of highly-effective intravascular recanalization therapy,” said Dr. Jeffrey L. Saver, professor of neurology and director of the Stroke Center at the University of California, Los Angeles, and lead investigator for one of the new studies.

In three of the four studies, the researchers did not report specific numbers on how selective they were in focusing in on the ischemic stroke patients most likely to benefit from this treatment, but the one study that did, EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial), run at nine Australian centers and one in New Zealand, showed the extensive winnowing that occurred. Of 7,796 patients with an acute ischemic stroke who initially presented, 1,044 (13%) were eligible to receive thrombolytic therapy (alteplase in this study). And from among these 1,044 patients, a mere 70 – less than 1% of the initial group – were deemed eligible for randomization into the embolectomy trial. The top three reasons for exclusion of patients who qualified for thrombolytic treatment from the trial was an absence of a major-vessel occlusion (45% of the excluded patients), presentation outside of the times when enrollment personnel were available (22%), and poor premorbid function (16%).

Mitchel L. Zoler/Frontline Medical News

But subgroup analyses in three of the four studies (EXTEND-IA with a total of 70 patients was too small for subgroup analyses) showed no subgroup of patients who failed to benefit from embolectomy, including elderly patients who in some cases were nonagenarians.

The unusual confluence of having four major trials showing remarkably consistent results meant that the stroke experts gathered at the meeting focused their attention not on whether stent retrievers should now be widely and routinely used in appropriate patients but instead on how this technology will roll out worldwide.

“From here on out we are obligated to treat patients with this technology at centers that can do this, and we are obligated to have more centers that can provide it,” said Dr. Kyra J. Becker, professor of neurology and neurological surgery and codirector of the Stroke Center at the University of Washington, Seattle. Dr. Becker had no involvement in any of the stent retriever trials. “I had been a doubter of this technology,” primarily because results reported at the International Stroke Conference a couple of years ago failed to prove the efficacy of clot retrieval in ischemic stroke patients, she noted. “Our ability to select appropriate patients and do it in a timely fashion hadn’t gotten to where it had to be until now,” Dr. Becker said in an interview.

“We only enrolled patients with blockages, we treated them quickly, and we used much better devices to open their arteries,” Dr. Saver added, explaining why the new studies succeeded when earlier studies had not.

The trial led by Dr. Saver, SWIFT-PRIME (SOLITAIRE™ FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), enrolled 195 patients at 39 sites in the United States and in Europe. At 90 days after treatment, 59 patients (60%) among those treated with thrombolysis plus embolectomy had a modified Rankin Scale score of 0-2, compared with 33 patients (36%) among those treated only with thrombolysis (in this trial intravenous treatment with tissue plasminogen activator), a highly significant difference for the study’s primary endpoint.

Mitchel L. Zoler/Frontline Medical News

“For every two and half patients treated, one more patient had a better disability outcome, and for every four patients treated, one more patient was independent at long-term follow-up,” Dr. Saver said. Safety measures were similar among patients in the study’s two arms.

The EXTEND-IA results showed a 90-day modified Rankin Scale score of 0-2 in 52% of the embolectomy patients, compared with 28% of those treated only with thrombolysis. The study’s co–primary endpoints were median level of reperfusion at 24 hours after treatment, 100% with embolectomy and 37% with thrombolysis only, and early neurologic recovery, defined as at least an 8-point drop from the baseline in the National Institutes of Health Stroke Scale score or a score of 0 or 1 when assessed 3 days after treatment. Patients met this second endpoint at an 80% rate with embolectomy and a 37% rate with thrombolysis only. Results of EXTEND-IA appeared in an article published online concurrently with the meeting report (N. Engl J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414792]).

The third, and largest, of the three studies presented at the conference, ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), enrolled 316 patients at 11 centers in Canada, 6 in the United States, 3 in South Korea, and 1 in Ireland. After 90 days, 53% of patients in the embolectomy arm had achieved a modified Rankin Scale score of 0-2, this study’s primary endpoint, compared with 29% of patients in the thrombolysis-only arm (treatment with alteplase). These results also appeared in an article published online concurrently with the conference report (N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905]).

SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NASHVILLE, TENN. – Treatment of selected patients with acute ischemic stroke underwent a dramatic, sudden shift with reports from three randomized, controlled trials that showed substantial added benefit and no incremental risk with the use of catheter-based embolic retrieval to open blocked intracerebral arteries when performed on top of standard thrombolytic therapy.

The three studies, each run independently and based in different countries, supported the results first reported last October and published online in December (N. Engl. J. Med. 2015;372:11-20) from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) study. These were the first contemporary trial results to show a jump in functional outcomes with use of a stent retriever catheter to pluck out the occluding embolus from an artery in the stroke patient’s brain to restore normal blood flow.

All three of the newly-reported studies stopped before reaching their prespecified enrollment levels because of overwhelming evidence for embolectomy’s incremental efficacy.

With four reports from prospective, randomized trials showing similar benefits and no added harm to patients, experts at the International Stroke Conference uniformly anointed catheter-based embolectomy the new standard of care for the small percentage of acute, ischemic-stroke patients who present with proximal, large-artery obstructions and also match the other strict clinical and imaging inclusion and exclusion criteria used in the studies.

Mitchel L. Zoler/Frontline Medical News

“Starting now, in patients with an acute ischemic stroke due to proximal vessel occlusion, rapid endovascular treatment using a retrieval stent is the standard of care,” Dr. Mayank Goyal declared from the plenary-session podium. He is a professor of diagnostic imaging at the University of Calgary (Canada) and an investigator in two of the three trials presented at the conference, which was sponsored by the American Heart Association.

“Today the world changed. We are now in a new era, the era of highly-effective intravascular recanalization therapy,” said Dr. Jeffrey L. Saver, professor of neurology and director of the Stroke Center at the University of California, Los Angeles, and lead investigator for one of the new studies.

In three of the four studies, the researchers did not report specific numbers on how selective they were in focusing in on the ischemic stroke patients most likely to benefit from this treatment, but the one study that did, EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial), run at nine Australian centers and one in New Zealand, showed the extensive winnowing that occurred. Of 7,796 patients with an acute ischemic stroke who initially presented, 1,044 (13%) were eligible to receive thrombolytic therapy (alteplase in this study). And from among these 1,044 patients, a mere 70 – less than 1% of the initial group – were deemed eligible for randomization into the embolectomy trial. The top three reasons for exclusion of patients who qualified for thrombolytic treatment from the trial was an absence of a major-vessel occlusion (45% of the excluded patients), presentation outside of the times when enrollment personnel were available (22%), and poor premorbid function (16%).

Mitchel L. Zoler/Frontline Medical News

But subgroup analyses in three of the four studies (EXTEND-IA with a total of 70 patients was too small for subgroup analyses) showed no subgroup of patients who failed to benefit from embolectomy, including elderly patients who in some cases were nonagenarians.

The unusual confluence of having four major trials showing remarkably consistent results meant that the stroke experts gathered at the meeting focused their attention not on whether stent retrievers should now be widely and routinely used in appropriate patients but instead on how this technology will roll out worldwide.

“From here on out we are obligated to treat patients with this technology at centers that can do this, and we are obligated to have more centers that can provide it,” said Dr. Kyra J. Becker, professor of neurology and neurological surgery and codirector of the Stroke Center at the University of Washington, Seattle. Dr. Becker had no involvement in any of the stent retriever trials. “I had been a doubter of this technology,” primarily because results reported at the International Stroke Conference a couple of years ago failed to prove the efficacy of clot retrieval in ischemic stroke patients, she noted. “Our ability to select appropriate patients and do it in a timely fashion hadn’t gotten to where it had to be until now,” Dr. Becker said in an interview.

“We only enrolled patients with blockages, we treated them quickly, and we used much better devices to open their arteries,” Dr. Saver added, explaining why the new studies succeeded when earlier studies had not.

The trial led by Dr. Saver, SWIFT-PRIME (SOLITAIRE™ FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), enrolled 195 patients at 39 sites in the United States and in Europe. At 90 days after treatment, 59 patients (60%) among those treated with thrombolysis plus embolectomy had a modified Rankin Scale score of 0-2, compared with 33 patients (36%) among those treated only with thrombolysis (in this trial intravenous treatment with tissue plasminogen activator), a highly significant difference for the study’s primary endpoint.

Mitchel L. Zoler/Frontline Medical News

“For every two and half patients treated, one more patient had a better disability outcome, and for every four patients treated, one more patient was independent at long-term follow-up,” Dr. Saver said. Safety measures were similar among patients in the study’s two arms.

The EXTEND-IA results showed a 90-day modified Rankin Scale score of 0-2 in 52% of the embolectomy patients, compared with 28% of those treated only with thrombolysis. The study’s co–primary endpoints were median level of reperfusion at 24 hours after treatment, 100% with embolectomy and 37% with thrombolysis only, and early neurologic recovery, defined as at least an 8-point drop from the baseline in the National Institutes of Health Stroke Scale score or a score of 0 or 1 when assessed 3 days after treatment. Patients met this second endpoint at an 80% rate with embolectomy and a 37% rate with thrombolysis only. Results of EXTEND-IA appeared in an article published online concurrently with the meeting report (N. Engl J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414792]).

The third, and largest, of the three studies presented at the conference, ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), enrolled 316 patients at 11 centers in Canada, 6 in the United States, 3 in South Korea, and 1 in Ireland. After 90 days, 53% of patients in the embolectomy arm had achieved a modified Rankin Scale score of 0-2, this study’s primary endpoint, compared with 29% of patients in the thrombolysis-only arm (treatment with alteplase). These results also appeared in an article published online concurrently with the conference report (N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905]).

SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NASHVILLE, TENN. – Treatment of selected patients with acute ischemic stroke underwent a dramatic, sudden shift with reports from three randomized, controlled trials that showed substantial added benefit and no incremental risk with the use of catheter-based embolic retrieval to open blocked intracerebral arteries when performed on top of standard thrombolytic therapy.

The three studies, each run independently and based in different countries, supported the results first reported last October and published online in December (N. Engl. J. Med. 2015;372:11-20) from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) study. These were the first contemporary trial results to show a jump in functional outcomes with use of a stent retriever catheter to pluck out the occluding embolus from an artery in the stroke patient’s brain to restore normal blood flow.

All three of the newly-reported studies stopped before reaching their prespecified enrollment levels because of overwhelming evidence for embolectomy’s incremental efficacy.

With four reports from prospective, randomized trials showing similar benefits and no added harm to patients, experts at the International Stroke Conference uniformly anointed catheter-based embolectomy the new standard of care for the small percentage of acute, ischemic-stroke patients who present with proximal, large-artery obstructions and also match the other strict clinical and imaging inclusion and exclusion criteria used in the studies.

Mitchel L. Zoler/Frontline Medical News

“Starting now, in patients with an acute ischemic stroke due to proximal vessel occlusion, rapid endovascular treatment using a retrieval stent is the standard of care,” Dr. Mayank Goyal declared from the plenary-session podium. He is a professor of diagnostic imaging at the University of Calgary (Canada) and an investigator in two of the three trials presented at the conference, which was sponsored by the American Heart Association.

“Today the world changed. We are now in a new era, the era of highly-effective intravascular recanalization therapy,” said Dr. Jeffrey L. Saver, professor of neurology and director of the Stroke Center at the University of California, Los Angeles, and lead investigator for one of the new studies.

In three of the four studies, the researchers did not report specific numbers on how selective they were in focusing in on the ischemic stroke patients most likely to benefit from this treatment, but the one study that did, EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial), run at nine Australian centers and one in New Zealand, showed the extensive winnowing that occurred. Of 7,796 patients with an acute ischemic stroke who initially presented, 1,044 (13%) were eligible to receive thrombolytic therapy (alteplase in this study). And from among these 1,044 patients, a mere 70 – less than 1% of the initial group – were deemed eligible for randomization into the embolectomy trial. The top three reasons for exclusion of patients who qualified for thrombolytic treatment from the trial was an absence of a major-vessel occlusion (45% of the excluded patients), presentation outside of the times when enrollment personnel were available (22%), and poor premorbid function (16%).

Mitchel L. Zoler/Frontline Medical News

But subgroup analyses in three of the four studies (EXTEND-IA with a total of 70 patients was too small for subgroup analyses) showed no subgroup of patients who failed to benefit from embolectomy, including elderly patients who in some cases were nonagenarians.

The unusual confluence of having four major trials showing remarkably consistent results meant that the stroke experts gathered at the meeting focused their attention not on whether stent retrievers should now be widely and routinely used in appropriate patients but instead on how this technology will roll out worldwide.

“From here on out we are obligated to treat patients with this technology at centers that can do this, and we are obligated to have more centers that can provide it,” said Dr. Kyra J. Becker, professor of neurology and neurological surgery and codirector of the Stroke Center at the University of Washington, Seattle. Dr. Becker had no involvement in any of the stent retriever trials. “I had been a doubter of this technology,” primarily because results reported at the International Stroke Conference a couple of years ago failed to prove the efficacy of clot retrieval in ischemic stroke patients, she noted. “Our ability to select appropriate patients and do it in a timely fashion hadn’t gotten to where it had to be until now,” Dr. Becker said in an interview.

“We only enrolled patients with blockages, we treated them quickly, and we used much better devices to open their arteries,” Dr. Saver added, explaining why the new studies succeeded when earlier studies had not.

The trial led by Dr. Saver, SWIFT-PRIME (SOLITAIRE™ FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), enrolled 195 patients at 39 sites in the United States and in Europe. At 90 days after treatment, 59 patients (60%) among those treated with thrombolysis plus embolectomy had a modified Rankin Scale score of 0-2, compared with 33 patients (36%) among those treated only with thrombolysis (in this trial intravenous treatment with tissue plasminogen activator), a highly significant difference for the study’s primary endpoint.

Mitchel L. Zoler/Frontline Medical News

“For every two and half patients treated, one more patient had a better disability outcome, and for every four patients treated, one more patient was independent at long-term follow-up,” Dr. Saver said. Safety measures were similar among patients in the study’s two arms.

The EXTEND-IA results showed a 90-day modified Rankin Scale score of 0-2 in 52% of the embolectomy patients, compared with 28% of those treated only with thrombolysis. The study’s co–primary endpoints were median level of reperfusion at 24 hours after treatment, 100% with embolectomy and 37% with thrombolysis only, and early neurologic recovery, defined as at least an 8-point drop from the baseline in the National Institutes of Health Stroke Scale score or a score of 0 or 1 when assessed 3 days after treatment. Patients met this second endpoint at an 80% rate with embolectomy and a 37% rate with thrombolysis only. Results of EXTEND-IA appeared in an article published online concurrently with the meeting report (N. Engl J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414792]).

The third, and largest, of the three studies presented at the conference, ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), enrolled 316 patients at 11 centers in Canada, 6 in the United States, 3 in South Korea, and 1 in Ireland. After 90 days, 53% of patients in the embolectomy arm had achieved a modified Rankin Scale score of 0-2, this study’s primary endpoint, compared with 29% of patients in the thrombolysis-only arm (treatment with alteplase). These results also appeared in an article published online concurrently with the conference report (N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905]).

SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler