VIDEO: Ischemic-stroke thrombectomy use widens and refines

LOS ANGELES – The use of endovascular thrombectomy in the United States to treat appropriate patients with acute ischemic stroke mushroomed during the past year, following several early-2015 reports that collectively documented the dramatic clinical benefit of the treatment.

As endovascular thrombectomy use grows, stroke centers are also refining and reshaping delivery of the treatment in concert with administration of intravenous tissue plasminogen activator (TPA; alteplase; Activase), which remains a key partner in producing best outcomes for acute ischemic-stroke patients with a proximal occlusion of a large cerebral artery. Collapsing delivery of the two treatments into a more seamless and streamlined process shaves critical minutes to treatment delivery, an approach called parallel processing. Recent findings have also emboldened stroke specialists to seriously consider simplifying the brain imaging that stroke patients receive prior to these treatments, a step that could further cut time to intervention while also making thrombectomy even more widely available.

Use of thrombectomy surges

The biggest endovascular thrombectomy news of the past year is how it has taken off for treating selected patients with acute ischemic stroke. “The rollout over the past year has been explosive. Everything pretty much shut down after the negative trial results in 2013, but now more hospitals are offering thrombectomy,” said Dr. Thomas A. Kent, professor of neurology and director of stroke research and education at Baylor College of Medicine in Houston, in an interview at the International Stroke Conference sponsored by the American Heart Association.

The best documentation of this surge came in a poster presented at the conference by researchers at the University of California, San Francisco. They analyzed data on treatment of 357,973 patients with acute ischemic stroke who were hospitalized at any one of 161 U.S. academic medical centers during October 2009-July 2015 and included in the University Healthsystem Consortium database. They tracked the percentage of patients treated endovascularly during each calendar quarter of the study period.

During 2009-2013, use of endovascular treatment rose steadily but gradually, from 1.5% of stroke patients in 2009 to 3.1% during the fourth quarter of 2012. Then, following three reports of no benefit from endovascular treatment presented at the International Stroke Conference in February 2013 – the IMS III, MR RESCUE, and SYNTHESIS trials – the endovascular rate dropped immediately and quickly bottomed out at a level of 2.6% that remained steady through the third quarter of 2014. But when the positive endovascular results from the MR CLEAN study became public in the final week of 2014, endovascular use began to quickly rise again, and then began to skyrocket during the first quarter of 2015 with three additional positive trial results reported during the Stroke Conference in February 2015. By the end of the second quarter of 2015, usage stood at 4.7%, representing a projected year-over-year increase of about 150% for all of 2015, compared with 2014, reported Dr. Anthony S. Kim, a vascular neurologist and medical director of the Stroke Center at the University of California, San Francisco, and his associates.

To put these percentages in perspective, experts estimate that roughly 10%-15% of all stroke patients qualify for thrombectomy intervention.

Their data also showed that the percentage of hospitals included in the database that performed endovascular therapies for stroke rose steadily from about 40% of centers in 2009 to nearly 60% by mid-2015.

“Endovascular therapy with newer-generation devices is increasingly part of standard treatment for acute ischemic stroke,” they said in their poster. In addition, they cited a “new urgency to evaluate regional access to embolectomy [another name for thrombectomy] nationally and to identify system-based solutions to improve access in underserved areas.”

Several stroke experts interviewed at the conference added their own anecdotal view of thrombectomy’s rapidly expanding use for appropriate acute ischemic stroke patients during 2015, and the need for continued effort to broaden its U.S. availability.

“The number of thrombectomies fell off after the negative 2013 trials and stayed flat until a year ago, but then jumped up. It has been very dramatic,” said Dr. Wade S. Smith, professor of neurology and director of the neurovascular service at the University of California, San Francisco.

“Thrombectomy use tremendously increased since February 2015,” said Dr. Mark J. Alberts, professor of neurology and medical director of the neurology service at the University of Texas Southwestern Medical Center in Dallas, in a video interview during the conference. But despite this growth, “the major challenge [today] is geography;” that is, reaching patients in suburban and rural areas who are not as close to the primarily urban medical centers that currently offer the procedure.

“We now have about 100 certified comprehensive stroke centers in the U.S.,” and by definition comprehensive stroke centers have the capability of treating patients with endovascular thrombectomy, noted Dr. Jeffrey Saver, professor of neurology and director of the stroke unit at the University of California, Los Angeles.

“Certification of these centers did not begin until about 2-3 years ago. But we probably need 300-400 of these centers” to provide thrombectomy to most U.S. stroke patients, he said. “A lot of additional hospitals are close to certification. I anticipate that over the next 1-2 years we will be in the neighborhood of having the number of centers we need,” Dr. Saver said in an interview.

Making thrombectomy better

In addition to expanding availability, the specifics of how endovascular thrombectomy gets delivered is evolving. A major trend is movement toward a “parallel processing” model, in which patients with an acute clinical presentation of a stroke amenable for endovascular treatment simultaneously undergo CT angiography to confirm and localize the large-artery clot causing their stroke, receive intravenous TPA, and undergo preparation for the endovascular access needed to remove the clot.

A pooled analysis of the recent, positive endovascular thrombectomy trials that was presented at the conference showed how quick you need to be to obtain a benefit from the procedures. “This gives us a starting point to further improve the target metrics for imaging and puncture times,” Dr. Saver said. “We want to shorten door-to-needle times for TPA and door-to-puncture times for thrombectomy, and the processes that need to be addressed for rapid delivery of both of these are very similar. We need for patients to only make a pit stop in the ED; we need to have the catheterization team ready to go in the thrombectomy suite within 30 minutes; and we need to emphasize speed in access to the target clot rather than time-consuming diagnostic angiography.”

“We now face the issue of how to best integrate TPA treatment and clot removal.” Dr. Kent said. “People are still trying to work that out. With parallel processing there is some overuse of resources: Some patients recover with TPA alone and don’t need thrombectomy. We are getting closer to the cardiology model of MI treatment. It’s now clear that there needs to be a simple, safe, effective way to do both TPA treatment and thrombectomy. We need to model ourselves on the cardiology experience.”

“If you can deal with the TPA decision in the same room without moving patients from room to room, from a scanner to a catheterization suite, you can really shorten the time to treatment,” Dr. Smith explained. “This is identical to the model that cardiologists have developed. We should now consider taking stroke patients directly to the angiography room in addition to administering TPA. We still need cross-sectional imaging, but the quality of the image from an angiography suite is probably sufficient to make a TPA decision. So you can start TPA while you are getting arterial access. The idea is simultaneous approaches to the patient instead of serial.”

“The whole system moves at the same time to eliminate wasted time,” Dr. Alberts summed up.

One of the big questions that has come up in this effort to speed up treatment and carve the quickest route to endovascular thrombectomy is whether TPA remains necessary. The skeptics’ position is, why waste time administering TPA if you’re also going to take out the offending clot?

The answer, at least for now, is that all signs indicate that giving TPA helps and is worth delivering.

“The 2015 thrombectomy trials had big differences among them in the dosage of TPA administered, and in the percentage of patients who received TPA. When 100% of patients received TPA they had the best outcomes,” Dr. Kent said. “There was a clear synergistic relationship between thrombectomy and TPA. There has been a trend to think about sending patients straight to thrombectomy and skipping TPA, but my colleagues and I think that we need to hold off on doing that. For now, if a patient is eligible to receive TPA they should get it and then quickly move to endovascular therapy. We are not yet ready to know it’s okay to go straight to endovascular treatment. In SWIFT-PRIME, it was pretty clear that the good outcomes were attributable to both [thrombectomy plus TPA]. Treating patients with TPA helps soften the clot to make it easier to remove, and improves flow through collateral arteries.”

“Our data in Memphis show that patients do better with thrombectomy plus intravenous TPA than on TPA alone,” agreed Dr. Lucas Elijovich, a neurologist at the University of Tennessee Health Science Center in Memphis, in an interview.

Simpler imaging also saves time

Although it’s not yet proven, another new wrinkle in working up acute ischemic-stroke patients for TPA and thrombectomy treatment is the idea that simpler and more widely available CT imaging, especially CT angiography of cerebral arteries, may suffice for confirming and localizing the culprit clot.

This concept received a significant boost at the International Stroke Conference in data reported from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial, yet another study that compared treatment with TPA alone with TPA plus endovascular thrombectomy, this time in 65 randomized patients treated at any of 11 U.K. centers. PISTE had a low enrollment level because the trial stopped prematurely, in July 2015, following the news that several fully completed trials had collectively established the superiority of endovascular thrombectomy plus TPA, thereby making it unethical to continue yet another randomized study.

This premature stoppage prevented PISTE from itself producing a statistically significant difference for its primary efficacy endpoint in favor of the combined treatment, although the results did show a nominal advantage to using thrombectomy plus TPA over TPA alone that was fully consistent with the other studies, Dr. Keith W. Muir reported at the conference.

But what made the PISTE results especially notable was that the trial achieved this consistent outcome with a “simpler” imaging protocol for patients during their workup that used only CT angiography, avoiding the cerebral CT perfusion imaging or MRI used in several of the other TPA-plus-thrombectomy versus TPA-only trials, noted Dr. Muir, professor of neuroscience and head of the stroke imaging group at the University of Glasgow.

“PISTE raises the question of how much imaging is necessary,” Dr. Kent commented.

“The PISTE results are exciting. A lot of us believe that all we need to know is that there is a blockage in a target vessel,” Dr. Smith said. “If we have that information, then we can identify a population of patients who will benefit from [thrombectomy]. CT angiography is simple and can easily fit into work flows.”

“PISTE used a very simple imaging system that makes thrombectomy even more applicable and generalizable to less resourced health systems,” Dr. Saver said. “Although the results from PISTE were not internally statistically significant because the trial ended early, the results were consistent with the external studies of thrombectomy, so it provides further evidence for benefit from thrombectomy.” And because the consistent results were achieved with simpler imaging it suggests simpler imaging may be all that’s needed.

“That’s a major question to wrestle with,” Dr. Saver suggested. “We need addition trials with a head-to-head comparison of simpler and more sophisticated imaging so we can tailor treatment to patients who would benefit from simpler and faster imaging.”

Dr. Kent had no disclosures. Dr. Kim has received research funding from SanBio and Biogen. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker. Dr. Alberts has been a consultant to Genentech. Dr. Saver has been a consultant to Stryker, Neuravi, Cognition Medical, Boehringer Ingelheim, and Medtronic. Dr. Elijovich has been a consultant to Stryker and Codman and received research support from Siemens. Dr. Muir has received research support from ReNeuron and unrestricted grants from Codman and Covidien.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – The use of endovascular thrombectomy in the United States to treat appropriate patients with acute ischemic stroke mushroomed during the past year, following several early-2015 reports that collectively documented the dramatic clinical benefit of the treatment.

As endovascular thrombectomy use grows, stroke centers are also refining and reshaping delivery of the treatment in concert with administration of intravenous tissue plasminogen activator (TPA; alteplase; Activase), which remains a key partner in producing best outcomes for acute ischemic-stroke patients with a proximal occlusion of a large cerebral artery. Collapsing delivery of the two treatments into a more seamless and streamlined process shaves critical minutes to treatment delivery, an approach called parallel processing. Recent findings have also emboldened stroke specialists to seriously consider simplifying the brain imaging that stroke patients receive prior to these treatments, a step that could further cut time to intervention while also making thrombectomy even more widely available.

Use of thrombectomy surges

The biggest endovascular thrombectomy news of the past year is how it has taken off for treating selected patients with acute ischemic stroke. “The rollout over the past year has been explosive. Everything pretty much shut down after the negative trial results in 2013, but now more hospitals are offering thrombectomy,” said Dr. Thomas A. Kent, professor of neurology and director of stroke research and education at Baylor College of Medicine in Houston, in an interview at the International Stroke Conference sponsored by the American Heart Association.

The best documentation of this surge came in a poster presented at the conference by researchers at the University of California, San Francisco. They analyzed data on treatment of 357,973 patients with acute ischemic stroke who were hospitalized at any one of 161 U.S. academic medical centers during October 2009-July 2015 and included in the University Healthsystem Consortium database. They tracked the percentage of patients treated endovascularly during each calendar quarter of the study period.

During 2009-2013, use of endovascular treatment rose steadily but gradually, from 1.5% of stroke patients in 2009 to 3.1% during the fourth quarter of 2012. Then, following three reports of no benefit from endovascular treatment presented at the International Stroke Conference in February 2013 – the IMS III, MR RESCUE, and SYNTHESIS trials – the endovascular rate dropped immediately and quickly bottomed out at a level of 2.6% that remained steady through the third quarter of 2014. But when the positive endovascular results from the MR CLEAN study became public in the final week of 2014, endovascular use began to quickly rise again, and then began to skyrocket during the first quarter of 2015 with three additional positive trial results reported during the Stroke Conference in February 2015. By the end of the second quarter of 2015, usage stood at 4.7%, representing a projected year-over-year increase of about 150% for all of 2015, compared with 2014, reported Dr. Anthony S. Kim, a vascular neurologist and medical director of the Stroke Center at the University of California, San Francisco, and his associates.

To put these percentages in perspective, experts estimate that roughly 10%-15% of all stroke patients qualify for thrombectomy intervention.

Their data also showed that the percentage of hospitals included in the database that performed endovascular therapies for stroke rose steadily from about 40% of centers in 2009 to nearly 60% by mid-2015.

“Endovascular therapy with newer-generation devices is increasingly part of standard treatment for acute ischemic stroke,” they said in their poster. In addition, they cited a “new urgency to evaluate regional access to embolectomy [another name for thrombectomy] nationally and to identify system-based solutions to improve access in underserved areas.”

Several stroke experts interviewed at the conference added their own anecdotal view of thrombectomy’s rapidly expanding use for appropriate acute ischemic stroke patients during 2015, and the need for continued effort to broaden its U.S. availability.

“The number of thrombectomies fell off after the negative 2013 trials and stayed flat until a year ago, but then jumped up. It has been very dramatic,” said Dr. Wade S. Smith, professor of neurology and director of the neurovascular service at the University of California, San Francisco.

“Thrombectomy use tremendously increased since February 2015,” said Dr. Mark J. Alberts, professor of neurology and medical director of the neurology service at the University of Texas Southwestern Medical Center in Dallas, in a video interview during the conference. But despite this growth, “the major challenge [today] is geography;” that is, reaching patients in suburban and rural areas who are not as close to the primarily urban medical centers that currently offer the procedure.

“We now have about 100 certified comprehensive stroke centers in the U.S.,” and by definition comprehensive stroke centers have the capability of treating patients with endovascular thrombectomy, noted Dr. Jeffrey Saver, professor of neurology and director of the stroke unit at the University of California, Los Angeles.

“Certification of these centers did not begin until about 2-3 years ago. But we probably need 300-400 of these centers” to provide thrombectomy to most U.S. stroke patients, he said. “A lot of additional hospitals are close to certification. I anticipate that over the next 1-2 years we will be in the neighborhood of having the number of centers we need,” Dr. Saver said in an interview.

Making thrombectomy better

In addition to expanding availability, the specifics of how endovascular thrombectomy gets delivered is evolving. A major trend is movement toward a “parallel processing” model, in which patients with an acute clinical presentation of a stroke amenable for endovascular treatment simultaneously undergo CT angiography to confirm and localize the large-artery clot causing their stroke, receive intravenous TPA, and undergo preparation for the endovascular access needed to remove the clot.

A pooled analysis of the recent, positive endovascular thrombectomy trials that was presented at the conference showed how quick you need to be to obtain a benefit from the procedures. “This gives us a starting point to further improve the target metrics for imaging and puncture times,” Dr. Saver said. “We want to shorten door-to-needle times for TPA and door-to-puncture times for thrombectomy, and the processes that need to be addressed for rapid delivery of both of these are very similar. We need for patients to only make a pit stop in the ED; we need to have the catheterization team ready to go in the thrombectomy suite within 30 minutes; and we need to emphasize speed in access to the target clot rather than time-consuming diagnostic angiography.”

“We now face the issue of how to best integrate TPA treatment and clot removal.” Dr. Kent said. “People are still trying to work that out. With parallel processing there is some overuse of resources: Some patients recover with TPA alone and don’t need thrombectomy. We are getting closer to the cardiology model of MI treatment. It’s now clear that there needs to be a simple, safe, effective way to do both TPA treatment and thrombectomy. We need to model ourselves on the cardiology experience.”

“If you can deal with the TPA decision in the same room without moving patients from room to room, from a scanner to a catheterization suite, you can really shorten the time to treatment,” Dr. Smith explained. “This is identical to the model that cardiologists have developed. We should now consider taking stroke patients directly to the angiography room in addition to administering TPA. We still need cross-sectional imaging, but the quality of the image from an angiography suite is probably sufficient to make a TPA decision. So you can start TPA while you are getting arterial access. The idea is simultaneous approaches to the patient instead of serial.”

“The whole system moves at the same time to eliminate wasted time,” Dr. Alberts summed up.

One of the big questions that has come up in this effort to speed up treatment and carve the quickest route to endovascular thrombectomy is whether TPA remains necessary. The skeptics’ position is, why waste time administering TPA if you’re also going to take out the offending clot?

The answer, at least for now, is that all signs indicate that giving TPA helps and is worth delivering.

“The 2015 thrombectomy trials had big differences among them in the dosage of TPA administered, and in the percentage of patients who received TPA. When 100% of patients received TPA they had the best outcomes,” Dr. Kent said. “There was a clear synergistic relationship between thrombectomy and TPA. There has been a trend to think about sending patients straight to thrombectomy and skipping TPA, but my colleagues and I think that we need to hold off on doing that. For now, if a patient is eligible to receive TPA they should get it and then quickly move to endovascular therapy. We are not yet ready to know it’s okay to go straight to endovascular treatment. In SWIFT-PRIME, it was pretty clear that the good outcomes were attributable to both [thrombectomy plus TPA]. Treating patients with TPA helps soften the clot to make it easier to remove, and improves flow through collateral arteries.”

“Our data in Memphis show that patients do better with thrombectomy plus intravenous TPA than on TPA alone,” agreed Dr. Lucas Elijovich, a neurologist at the University of Tennessee Health Science Center in Memphis, in an interview.

Simpler imaging also saves time

Although it’s not yet proven, another new wrinkle in working up acute ischemic-stroke patients for TPA and thrombectomy treatment is the idea that simpler and more widely available CT imaging, especially CT angiography of cerebral arteries, may suffice for confirming and localizing the culprit clot.

This concept received a significant boost at the International Stroke Conference in data reported from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial, yet another study that compared treatment with TPA alone with TPA plus endovascular thrombectomy, this time in 65 randomized patients treated at any of 11 U.K. centers. PISTE had a low enrollment level because the trial stopped prematurely, in July 2015, following the news that several fully completed trials had collectively established the superiority of endovascular thrombectomy plus TPA, thereby making it unethical to continue yet another randomized study.

This premature stoppage prevented PISTE from itself producing a statistically significant difference for its primary efficacy endpoint in favor of the combined treatment, although the results did show a nominal advantage to using thrombectomy plus TPA over TPA alone that was fully consistent with the other studies, Dr. Keith W. Muir reported at the conference.

But what made the PISTE results especially notable was that the trial achieved this consistent outcome with a “simpler” imaging protocol for patients during their workup that used only CT angiography, avoiding the cerebral CT perfusion imaging or MRI used in several of the other TPA-plus-thrombectomy versus TPA-only trials, noted Dr. Muir, professor of neuroscience and head of the stroke imaging group at the University of Glasgow.

“PISTE raises the question of how much imaging is necessary,” Dr. Kent commented.

“The PISTE results are exciting. A lot of us believe that all we need to know is that there is a blockage in a target vessel,” Dr. Smith said. “If we have that information, then we can identify a population of patients who will benefit from [thrombectomy]. CT angiography is simple and can easily fit into work flows.”

“PISTE used a very simple imaging system that makes thrombectomy even more applicable and generalizable to less resourced health systems,” Dr. Saver said. “Although the results from PISTE were not internally statistically significant because the trial ended early, the results were consistent with the external studies of thrombectomy, so it provides further evidence for benefit from thrombectomy.” And because the consistent results were achieved with simpler imaging it suggests simpler imaging may be all that’s needed.

“That’s a major question to wrestle with,” Dr. Saver suggested. “We need addition trials with a head-to-head comparison of simpler and more sophisticated imaging so we can tailor treatment to patients who would benefit from simpler and faster imaging.”

Dr. Kent had no disclosures. Dr. Kim has received research funding from SanBio and Biogen. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker. Dr. Alberts has been a consultant to Genentech. Dr. Saver has been a consultant to Stryker, Neuravi, Cognition Medical, Boehringer Ingelheim, and Medtronic. Dr. Elijovich has been a consultant to Stryker and Codman and received research support from Siemens. Dr. Muir has received research support from ReNeuron and unrestricted grants from Codman and Covidien.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – The use of endovascular thrombectomy in the United States to treat appropriate patients with acute ischemic stroke mushroomed during the past year, following several early-2015 reports that collectively documented the dramatic clinical benefit of the treatment.

As endovascular thrombectomy use grows, stroke centers are also refining and reshaping delivery of the treatment in concert with administration of intravenous tissue plasminogen activator (TPA; alteplase; Activase), which remains a key partner in producing best outcomes for acute ischemic-stroke patients with a proximal occlusion of a large cerebral artery. Collapsing delivery of the two treatments into a more seamless and streamlined process shaves critical minutes to treatment delivery, an approach called parallel processing. Recent findings have also emboldened stroke specialists to seriously consider simplifying the brain imaging that stroke patients receive prior to these treatments, a step that could further cut time to intervention while also making thrombectomy even more widely available.

Use of thrombectomy surges

The biggest endovascular thrombectomy news of the past year is how it has taken off for treating selected patients with acute ischemic stroke. “The rollout over the past year has been explosive. Everything pretty much shut down after the negative trial results in 2013, but now more hospitals are offering thrombectomy,” said Dr. Thomas A. Kent, professor of neurology and director of stroke research and education at Baylor College of Medicine in Houston, in an interview at the International Stroke Conference sponsored by the American Heart Association.

The best documentation of this surge came in a poster presented at the conference by researchers at the University of California, San Francisco. They analyzed data on treatment of 357,973 patients with acute ischemic stroke who were hospitalized at any one of 161 U.S. academic medical centers during October 2009-July 2015 and included in the University Healthsystem Consortium database. They tracked the percentage of patients treated endovascularly during each calendar quarter of the study period.

During 2009-2013, use of endovascular treatment rose steadily but gradually, from 1.5% of stroke patients in 2009 to 3.1% during the fourth quarter of 2012. Then, following three reports of no benefit from endovascular treatment presented at the International Stroke Conference in February 2013 – the IMS III, MR RESCUE, and SYNTHESIS trials – the endovascular rate dropped immediately and quickly bottomed out at a level of 2.6% that remained steady through the third quarter of 2014. But when the positive endovascular results from the MR CLEAN study became public in the final week of 2014, endovascular use began to quickly rise again, and then began to skyrocket during the first quarter of 2015 with three additional positive trial results reported during the Stroke Conference in February 2015. By the end of the second quarter of 2015, usage stood at 4.7%, representing a projected year-over-year increase of about 150% for all of 2015, compared with 2014, reported Dr. Anthony S. Kim, a vascular neurologist and medical director of the Stroke Center at the University of California, San Francisco, and his associates.

To put these percentages in perspective, experts estimate that roughly 10%-15% of all stroke patients qualify for thrombectomy intervention.

Their data also showed that the percentage of hospitals included in the database that performed endovascular therapies for stroke rose steadily from about 40% of centers in 2009 to nearly 60% by mid-2015.

“Endovascular therapy with newer-generation devices is increasingly part of standard treatment for acute ischemic stroke,” they said in their poster. In addition, they cited a “new urgency to evaluate regional access to embolectomy [another name for thrombectomy] nationally and to identify system-based solutions to improve access in underserved areas.”

Several stroke experts interviewed at the conference added their own anecdotal view of thrombectomy’s rapidly expanding use for appropriate acute ischemic stroke patients during 2015, and the need for continued effort to broaden its U.S. availability.

“The number of thrombectomies fell off after the negative 2013 trials and stayed flat until a year ago, but then jumped up. It has been very dramatic,” said Dr. Wade S. Smith, professor of neurology and director of the neurovascular service at the University of California, San Francisco.

“Thrombectomy use tremendously increased since February 2015,” said Dr. Mark J. Alberts, professor of neurology and medical director of the neurology service at the University of Texas Southwestern Medical Center in Dallas, in a video interview during the conference. But despite this growth, “the major challenge [today] is geography;” that is, reaching patients in suburban and rural areas who are not as close to the primarily urban medical centers that currently offer the procedure.

“We now have about 100 certified comprehensive stroke centers in the U.S.,” and by definition comprehensive stroke centers have the capability of treating patients with endovascular thrombectomy, noted Dr. Jeffrey Saver, professor of neurology and director of the stroke unit at the University of California, Los Angeles.

“Certification of these centers did not begin until about 2-3 years ago. But we probably need 300-400 of these centers” to provide thrombectomy to most U.S. stroke patients, he said. “A lot of additional hospitals are close to certification. I anticipate that over the next 1-2 years we will be in the neighborhood of having the number of centers we need,” Dr. Saver said in an interview.

Making thrombectomy better

In addition to expanding availability, the specifics of how endovascular thrombectomy gets delivered is evolving. A major trend is movement toward a “parallel processing” model, in which patients with an acute clinical presentation of a stroke amenable for endovascular treatment simultaneously undergo CT angiography to confirm and localize the large-artery clot causing their stroke, receive intravenous TPA, and undergo preparation for the endovascular access needed to remove the clot.

A pooled analysis of the recent, positive endovascular thrombectomy trials that was presented at the conference showed how quick you need to be to obtain a benefit from the procedures. “This gives us a starting point to further improve the target metrics for imaging and puncture times,” Dr. Saver said. “We want to shorten door-to-needle times for TPA and door-to-puncture times for thrombectomy, and the processes that need to be addressed for rapid delivery of both of these are very similar. We need for patients to only make a pit stop in the ED; we need to have the catheterization team ready to go in the thrombectomy suite within 30 minutes; and we need to emphasize speed in access to the target clot rather than time-consuming diagnostic angiography.”

“We now face the issue of how to best integrate TPA treatment and clot removal.” Dr. Kent said. “People are still trying to work that out. With parallel processing there is some overuse of resources: Some patients recover with TPA alone and don’t need thrombectomy. We are getting closer to the cardiology model of MI treatment. It’s now clear that there needs to be a simple, safe, effective way to do both TPA treatment and thrombectomy. We need to model ourselves on the cardiology experience.”

“If you can deal with the TPA decision in the same room without moving patients from room to room, from a scanner to a catheterization suite, you can really shorten the time to treatment,” Dr. Smith explained. “This is identical to the model that cardiologists have developed. We should now consider taking stroke patients directly to the angiography room in addition to administering TPA. We still need cross-sectional imaging, but the quality of the image from an angiography suite is probably sufficient to make a TPA decision. So you can start TPA while you are getting arterial access. The idea is simultaneous approaches to the patient instead of serial.”

“The whole system moves at the same time to eliminate wasted time,” Dr. Alberts summed up.

One of the big questions that has come up in this effort to speed up treatment and carve the quickest route to endovascular thrombectomy is whether TPA remains necessary. The skeptics’ position is, why waste time administering TPA if you’re also going to take out the offending clot?

The answer, at least for now, is that all signs indicate that giving TPA helps and is worth delivering.

“The 2015 thrombectomy trials had big differences among them in the dosage of TPA administered, and in the percentage of patients who received TPA. When 100% of patients received TPA they had the best outcomes,” Dr. Kent said. “There was a clear synergistic relationship between thrombectomy and TPA. There has been a trend to think about sending patients straight to thrombectomy and skipping TPA, but my colleagues and I think that we need to hold off on doing that. For now, if a patient is eligible to receive TPA they should get it and then quickly move to endovascular therapy. We are not yet ready to know it’s okay to go straight to endovascular treatment. In SWIFT-PRIME, it was pretty clear that the good outcomes were attributable to both [thrombectomy plus TPA]. Treating patients with TPA helps soften the clot to make it easier to remove, and improves flow through collateral arteries.”

“Our data in Memphis show that patients do better with thrombectomy plus intravenous TPA than on TPA alone,” agreed Dr. Lucas Elijovich, a neurologist at the University of Tennessee Health Science Center in Memphis, in an interview.

Simpler imaging also saves time

Although it’s not yet proven, another new wrinkle in working up acute ischemic-stroke patients for TPA and thrombectomy treatment is the idea that simpler and more widely available CT imaging, especially CT angiography of cerebral arteries, may suffice for confirming and localizing the culprit clot.

This concept received a significant boost at the International Stroke Conference in data reported from the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) trial, yet another study that compared treatment with TPA alone with TPA plus endovascular thrombectomy, this time in 65 randomized patients treated at any of 11 U.K. centers. PISTE had a low enrollment level because the trial stopped prematurely, in July 2015, following the news that several fully completed trials had collectively established the superiority of endovascular thrombectomy plus TPA, thereby making it unethical to continue yet another randomized study.

This premature stoppage prevented PISTE from itself producing a statistically significant difference for its primary efficacy endpoint in favor of the combined treatment, although the results did show a nominal advantage to using thrombectomy plus TPA over TPA alone that was fully consistent with the other studies, Dr. Keith W. Muir reported at the conference.

But what made the PISTE results especially notable was that the trial achieved this consistent outcome with a “simpler” imaging protocol for patients during their workup that used only CT angiography, avoiding the cerebral CT perfusion imaging or MRI used in several of the other TPA-plus-thrombectomy versus TPA-only trials, noted Dr. Muir, professor of neuroscience and head of the stroke imaging group at the University of Glasgow.

“PISTE raises the question of how much imaging is necessary,” Dr. Kent commented.

“The PISTE results are exciting. A lot of us believe that all we need to know is that there is a blockage in a target vessel,” Dr. Smith said. “If we have that information, then we can identify a population of patients who will benefit from [thrombectomy]. CT angiography is simple and can easily fit into work flows.”

“PISTE used a very simple imaging system that makes thrombectomy even more applicable and generalizable to less resourced health systems,” Dr. Saver said. “Although the results from PISTE were not internally statistically significant because the trial ended early, the results were consistent with the external studies of thrombectomy, so it provides further evidence for benefit from thrombectomy.” And because the consistent results were achieved with simpler imaging it suggests simpler imaging may be all that’s needed.

“That’s a major question to wrestle with,” Dr. Saver suggested. “We need addition trials with a head-to-head comparison of simpler and more sophisticated imaging so we can tailor treatment to patients who would benefit from simpler and faster imaging.”

Dr. Kent had no disclosures. Dr. Kim has received research funding from SanBio and Biogen. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker. Dr. Alberts has been a consultant to Genentech. Dr. Saver has been a consultant to Stryker, Neuravi, Cognition Medical, Boehringer Ingelheim, and Medtronic. Dr. Elijovich has been a consultant to Stryker and Codman and received research support from Siemens. Dr. Muir has received research support from ReNeuron and unrestricted grants from Codman and Covidien.

mzoler@frontlinemedcom.com

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