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LAS VEGAS—Recent changes in the labeling of t-PA, along with FDA approval of a clot retrieval device, are increasing the pressure for clinicians to consider aggressive treatment of acute stroke in a broader range of patients, according to an update at the American Academy of Neurology’s Fall 2016 Conference. These changes have been shifting the orientation so that t-PA is not just an option, but is now widely regarded as a benchmark for quality of care at centers where acute stroke is treated.
Offering patients with acute stroke this lytic agent “has also become an incredibly important legal benchmark, as there is reportedly more litigation ... in regard to missing opportunities to administer t-PA rather than as a result of complications of t-PA administration,” said Natalia S. Rost, MD, Director of Acute Stroke Services at Massachusetts General Hospital in Boston. Delivering the update on acute stroke, Dr. Rost said it is important that clinicians adjust to these label changes to increase the proportion of eligible patients who receive t-PA, which she characterized as “the only FDA-approved medication shown to improve stroke outcomes.” 
Reconsidering Contraindications
The major risk of t-PA is potentially life-threatening bleeding events, which is the basis for most contraindications and the source of hesitation for many clinicians concerned about an iatrogenic complication. However, more than a decade of experience has demonstrated that the benefit-to-risk ratio favors treatment in many patients originally listed as contraindicated. A reevaluation of the evidence by an American Heart Association/American Stroke Association (AHA/ASA) joint committee contributed to the 2015 decision to adjust the labeling.
“For example, the history of prior stroke as a contraindication has been removed entirely,” Dr. Rost said. Other examples singled out by Dr. Rost include patients who had a seizure at stroke onset, patients with mild stroke, patients with severe stroke, patients with early signs of infarction on CT scan, and patients with diabetes.
In other cases, absolute contraindications have been relisted as warnings. These include elderly age, history of gastrointestinal bleeding, and pregnancy. Severe and difficult-to-control hypertension and history of subarachnoid hemorrhage remain contraindications, but Dr. Rost noted that the specifics have been removed, permitting some discretion in how these terms are defined.
While loosening of the contraindications for t-PA is designed to increase the proportion of patients who receive this potentially life-saving therapy, the relisting of the indications may also bring more rigor to clinical practice. A review by Demaerschalk et al included a survey of clinicians that showed wide variability in practice. The survey showed that less than 40% of clinicians reported that they were willing to administer t-PA to patients who had had a myocardial infarction in the previous three months; less than 20% reported a willingness to administer t-PA to patients who had had major surgery in the previous 14 days.
Stroke specialists have long considered t-PA to be the standard of care for patients with stroke presenting within three hours of symptoms, but the AHA/ASA review of safety data has shifted the orientation. Dr. Rost said that clinicians should no longer consider t-PA among other options in patients presenting within three hours of symptom onset, but rather “assume t-PA treatment unless contraindicated.”
Intra-Arterial Thrombolysis
There have also been recent changes in regard to the indications of intra-arterial thrombolysis devices in conjunction with t-PA. Various mechanical devices for removing clots associated with stroke (ie, mechanical thrombectomy) have been available for more than 10 years, but were not initially supported by evidence that they improved functional outcomes. This situation has changed, according to Dr. Rost. She gave credit to stent retrievers, the most recent evolution in mechanical devices, which provide “almost an immediate path to reperfusion.” She called the technology instrumental to the clinical benefits now being seen.
Although the first multicenter trial to demonstrate an improvement in functional independence, MR CLEAN, was published in December 2014, there have been several subsequent trials, including ESCAPE, EXTEND-IA, and SWIFT-PRIME, all showing similar benefits of mechanical thrombectomy when conducted under standardized patient selection criteria.
More data are likely to be coming, according to Dr. Rost, but the AHA/ASA guidelines for intra-arterial thrombolysis have already been revised. According to the 2015 update published in Stroke, patients should be considered for endovascular therapy with a stent retriever if they have an occlusion in the internal carotid artery or proximal middle cerebral artery, age of at least 18, modified Rankin Scale score no higher than 1, NIH Stroke Scale (NIHSS) score of at least 6, and an Alberta Stroke Program Early CT Score (ASPECTS) of at least 6.
These guidelines further specify that groin puncture for this procedure must be initiated within six hours of symptom onset. The update highlights that all patients presenting within 4.5 hours of symptom onset should be considered for treatment with t-PA prior to consideration of mechanical thrombectomy.
On September 2, 2016, the “FDA for the first time approved a mechanical device for the indication of improvement in functional outcome,” said Dr. Rost. The approval included devices that were used strictly within six hours of symptom onset and only following treatment with t-PA in the first three hours of stroke. The new labeling is specific for the Trevo ProVue and Trevo XP ProVue clot retrieval devices, but Dr. Rost predicted that many of the other devices using similar technology will eventually receive the same approval.
Stroke Science Continues to Evolve
The adage that time is brain in acute stroke is well known, but it was recently reinforced in a meta-analysis of thrombectomy trials that demonstrated that most benefit from stroke treatments is achieved if reperfusion occurs within seven hours of symptom onset. Citing data from Saver et al, Dr. Rost reiterated the importance of adhering to recommendations for early administration of the most effective therapies to improve functional outcomes.
Although clinicians should know and adhere to guidelines to deliver acute stroke treatments to patients “proven to benefit from these therapies,” Dr. Rost expects the guidelines to continue to evolve with new studies and more experience, particularly with mechanical endovascular devices. “Just as we have recently seen with t-PA, we may in time be able to relax the parameters of who is treated [with these devices],” Dr. Rost said.
Dr. Rost reported financial relationships with BioTelemetry, Daiichi Sankyo, Genzyme, and Omniox.
—Theodore Bosworth
Suggested Reading
Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11-20.
Demaerschalk BM, Kleindorfer Do, Adeoye OM, et al. Scientific rationale for the inclusion and exlusion criteria for intravenous alteplase in acute ischemeic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581-641.
Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(10):3020-3035.
Saver JL, Goyal M, van der Lugt A, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA. 2016;316(12):1279-1288.
LAS VEGAS—Recent changes in the labeling of t-PA, along with FDA approval of a clot retrieval device, are increasing the pressure for clinicians to consider aggressive treatment of acute stroke in a broader range of patients, according to an update at the American Academy of Neurology’s Fall 2016 Conference. These changes have been shifting the orientation so that t-PA is not just an option, but is now widely regarded as a benchmark for quality of care at centers where acute stroke is treated.
Offering patients with acute stroke this lytic agent “has also become an incredibly important legal benchmark, as there is reportedly more litigation ... in regard to missing opportunities to administer t-PA rather than as a result of complications of t-PA administration,” said Natalia S. Rost, MD, Director of Acute Stroke Services at Massachusetts General Hospital in Boston. Delivering the update on acute stroke, Dr. Rost said it is important that clinicians adjust to these label changes to increase the proportion of eligible patients who receive t-PA, which she characterized as “the only FDA-approved medication shown to improve stroke outcomes.”
Reconsidering Contraindications
The major risk of t-PA is potentially life-threatening bleeding events, which is the basis for most contraindications and the source of hesitation for many clinicians concerned about an iatrogenic complication. However, more than a decade of experience has demonstrated that the benefit-to-risk ratio favors treatment in many patients originally listed as contraindicated. A reevaluation of the evidence by an American Heart Association/American Stroke Association (AHA/ASA) joint committee contributed to the 2015 decision to adjust the labeling.
“For example, the history of prior stroke as a contraindication has been removed entirely,” Dr. Rost said. Other examples singled out by Dr. Rost include patients who had a seizure at stroke onset, patients with mild stroke, patients with severe stroke, patients with early signs of infarction on CT scan, and patients with diabetes.
In other cases, absolute contraindications have been relisted as warnings. These include elderly age, history of gastrointestinal bleeding, and pregnancy. Severe and difficult-to-control hypertension and history of subarachnoid hemorrhage remain contraindications, but Dr. Rost noted that the specifics have been removed, permitting some discretion in how these terms are defined.
While loosening of the contraindications for t-PA is designed to increase the proportion of patients who receive this potentially life-saving therapy, the relisting of the indications may also bring more rigor to clinical practice. A review by Demaerschalk et al included a survey of clinicians that showed wide variability in practice. The survey showed that less than 40% of clinicians reported that they were willing to administer t-PA to patients who had had a myocardial infarction in the previous three months; less than 20% reported a willingness to administer t-PA to patients who had had major surgery in the previous 14 days.
Stroke specialists have long considered t-PA to be the standard of care for patients with stroke presenting within three hours of symptoms, but the AHA/ASA review of safety data has shifted the orientation. Dr. Rost said that clinicians should no longer consider t-PA among other options in patients presenting within three hours of symptom onset, but rather “assume t-PA treatment unless contraindicated.”
Intra-Arterial Thrombolysis
There have also been recent changes in regard to the indications of intra-arterial thrombolysis devices in conjunction with t-PA. Various mechanical devices for removing clots associated with stroke (ie, mechanical thrombectomy) have been available for more than 10 years, but were not initially supported by evidence that they improved functional outcomes. This situation has changed, according to Dr. Rost. She gave credit to stent retrievers, the most recent evolution in mechanical devices, which provide “almost an immediate path to reperfusion.” She called the technology instrumental to the clinical benefits now being seen.
Although the first multicenter trial to demonstrate an improvement in functional independence, MR CLEAN, was published in December 2014, there have been several subsequent trials, including ESCAPE, EXTEND-IA, and SWIFT-PRIME, all showing similar benefits of mechanical thrombectomy when conducted under standardized patient selection criteria.
More data are likely to be coming, according to Dr. Rost, but the AHA/ASA guidelines for intra-arterial thrombolysis have already been revised. According to the 2015 update published in Stroke, patients should be considered for endovascular therapy with a stent retriever if they have an occlusion in the internal carotid artery or proximal middle cerebral artery, age of at least 18, modified Rankin Scale score no higher than 1, NIH Stroke Scale (NIHSS) score of at least 6, and an Alberta Stroke Program Early CT Score (ASPECTS) of at least 6.
These guidelines further specify that groin puncture for this procedure must be initiated within six hours of symptom onset. The update highlights that all patients presenting within 4.5 hours of symptom onset should be considered for treatment with t-PA prior to consideration of mechanical thrombectomy.
On September 2, 2016, the “FDA for the first time approved a mechanical device for the indication of improvement in functional outcome,” said Dr. Rost. The approval included devices that were used strictly within six hours of symptom onset and only following treatment with t-PA in the first three hours of stroke. The new labeling is specific for the Trevo ProVue and Trevo XP ProVue clot retrieval devices, but Dr. Rost predicted that many of the other devices using similar technology will eventually receive the same approval.
Stroke Science Continues to Evolve
The adage that time is brain in acute stroke is well known, but it was recently reinforced in a meta-analysis of thrombectomy trials that demonstrated that most benefit from stroke treatments is achieved if reperfusion occurs within seven hours of symptom onset. Citing data from Saver et al, Dr. Rost reiterated the importance of adhering to recommendations for early administration of the most effective therapies to improve functional outcomes.
Although clinicians should know and adhere to guidelines to deliver acute stroke treatments to patients “proven to benefit from these therapies,” Dr. Rost expects the guidelines to continue to evolve with new studies and more experience, particularly with mechanical endovascular devices. “Just as we have recently seen with t-PA, we may in time be able to relax the parameters of who is treated [with these devices],” Dr. Rost said.
Dr. Rost reported financial relationships with BioTelemetry, Daiichi Sankyo, Genzyme, and Omniox.
—Theodore Bosworth
Suggested Reading
Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11-20.
Demaerschalk BM, Kleindorfer Do, Adeoye OM, et al. Scientific rationale for the inclusion and exlusion criteria for intravenous alteplase in acute ischemeic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581-641.
Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(10):3020-3035.
Saver JL, Goyal M, van der Lugt A, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA. 2016;316(12):1279-1288.
LAS VEGAS—Recent changes in the labeling of t-PA, along with FDA approval of a clot retrieval device, are increasing the pressure for clinicians to consider aggressive treatment of acute stroke in a broader range of patients, according to an update at the American Academy of Neurology’s Fall 2016 Conference. These changes have been shifting the orientation so that t-PA is not just an option, but is now widely regarded as a benchmark for quality of care at centers where acute stroke is treated.
Offering patients with acute stroke this lytic agent “has also become an incredibly important legal benchmark, as there is reportedly more litigation ... in regard to missing opportunities to administer t-PA rather than as a result of complications of t-PA administration,” said Natalia S. Rost, MD, Director of Acute Stroke Services at Massachusetts General Hospital in Boston. Delivering the update on acute stroke, Dr. Rost said it is important that clinicians adjust to these label changes to increase the proportion of eligible patients who receive t-PA, which she characterized as “the only FDA-approved medication shown to improve stroke outcomes.”
Reconsidering Contraindications
The major risk of t-PA is potentially life-threatening bleeding events, which is the basis for most contraindications and the source of hesitation for many clinicians concerned about an iatrogenic complication. However, more than a decade of experience has demonstrated that the benefit-to-risk ratio favors treatment in many patients originally listed as contraindicated. A reevaluation of the evidence by an American Heart Association/American Stroke Association (AHA/ASA) joint committee contributed to the 2015 decision to adjust the labeling.
“For example, the history of prior stroke as a contraindication has been removed entirely,” Dr. Rost said. Other examples singled out by Dr. Rost include patients who had a seizure at stroke onset, patients with mild stroke, patients with severe stroke, patients with early signs of infarction on CT scan, and patients with diabetes.
In other cases, absolute contraindications have been relisted as warnings. These include elderly age, history of gastrointestinal bleeding, and pregnancy. Severe and difficult-to-control hypertension and history of subarachnoid hemorrhage remain contraindications, but Dr. Rost noted that the specifics have been removed, permitting some discretion in how these terms are defined.
While loosening of the contraindications for t-PA is designed to increase the proportion of patients who receive this potentially life-saving therapy, the relisting of the indications may also bring more rigor to clinical practice. A review by Demaerschalk et al included a survey of clinicians that showed wide variability in practice. The survey showed that less than 40% of clinicians reported that they were willing to administer t-PA to patients who had had a myocardial infarction in the previous three months; less than 20% reported a willingness to administer t-PA to patients who had had major surgery in the previous 14 days.
Stroke specialists have long considered t-PA to be the standard of care for patients with stroke presenting within three hours of symptoms, but the AHA/ASA review of safety data has shifted the orientation. Dr. Rost said that clinicians should no longer consider t-PA among other options in patients presenting within three hours of symptom onset, but rather “assume t-PA treatment unless contraindicated.”
Intra-Arterial Thrombolysis
There have also been recent changes in regard to the indications of intra-arterial thrombolysis devices in conjunction with t-PA. Various mechanical devices for removing clots associated with stroke (ie, mechanical thrombectomy) have been available for more than 10 years, but were not initially supported by evidence that they improved functional outcomes. This situation has changed, according to Dr. Rost. She gave credit to stent retrievers, the most recent evolution in mechanical devices, which provide “almost an immediate path to reperfusion.” She called the technology instrumental to the clinical benefits now being seen.
Although the first multicenter trial to demonstrate an improvement in functional independence, MR CLEAN, was published in December 2014, there have been several subsequent trials, including ESCAPE, EXTEND-IA, and SWIFT-PRIME, all showing similar benefits of mechanical thrombectomy when conducted under standardized patient selection criteria.
More data are likely to be coming, according to Dr. Rost, but the AHA/ASA guidelines for intra-arterial thrombolysis have already been revised. According to the 2015 update published in Stroke, patients should be considered for endovascular therapy with a stent retriever if they have an occlusion in the internal carotid artery or proximal middle cerebral artery, age of at least 18, modified Rankin Scale score no higher than 1, NIH Stroke Scale (NIHSS) score of at least 6, and an Alberta Stroke Program Early CT Score (ASPECTS) of at least 6.
These guidelines further specify that groin puncture for this procedure must be initiated within six hours of symptom onset. The update highlights that all patients presenting within 4.5 hours of symptom onset should be considered for treatment with t-PA prior to consideration of mechanical thrombectomy.
On September 2, 2016, the “FDA for the first time approved a mechanical device for the indication of improvement in functional outcome,” said Dr. Rost. The approval included devices that were used strictly within six hours of symptom onset and only following treatment with t-PA in the first three hours of stroke. The new labeling is specific for the Trevo ProVue and Trevo XP ProVue clot retrieval devices, but Dr. Rost predicted that many of the other devices using similar technology will eventually receive the same approval.
Stroke Science Continues to Evolve
The adage that time is brain in acute stroke is well known, but it was recently reinforced in a meta-analysis of thrombectomy trials that demonstrated that most benefit from stroke treatments is achieved if reperfusion occurs within seven hours of symptom onset. Citing data from Saver et al, Dr. Rost reiterated the importance of adhering to recommendations for early administration of the most effective therapies to improve functional outcomes.
Although clinicians should know and adhere to guidelines to deliver acute stroke treatments to patients “proven to benefit from these therapies,” Dr. Rost expects the guidelines to continue to evolve with new studies and more experience, particularly with mechanical endovascular devices. “Just as we have recently seen with t-PA, we may in time be able to relax the parameters of who is treated [with these devices],” Dr. Rost said.
Dr. Rost reported financial relationships with BioTelemetry, Daiichi Sankyo, Genzyme, and Omniox.
—Theodore Bosworth
Suggested Reading
Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11-20.
Demaerschalk BM, Kleindorfer Do, Adeoye OM, et al. Scientific rationale for the inclusion and exlusion criteria for intravenous alteplase in acute ischemeic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581-641.
Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(10):3020-3035.
Saver JL, Goyal M, van der Lugt A, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA. 2016;316(12):1279-1288.
