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Two new noninferiority trials address the controversial question of whether thrombolytic therapy can be omitted for acute ischemic stroke in patients undergoing endovascular thrombectomy for large-vessel occlusion.
Both trials show better outcomes when standard bridging thrombolytic therapy is used before thrombectomy, with comparable safety.
The results of SWIFT-DIRECT and DIRECT-SAFE were published online June 22 in The Lancet.
“The case appears closed. Bypass intravenous thrombolysis is highly unlikely to be noninferior to standard care by a clinically acceptable margin for most patients,” writes Pooja Khatri, MD, MSc, department of neurology, University of Cincinnati, in a linked comment.
SWIFT-DIRECT
SWIFT-DIRECT enrolled 408 patients (median age 72; 51% women) with acute stroke due to large vessel occlusion admitted to stroke centers in Europe and Canada. Half were randomly allocated to thrombectomy alone and half to intravenous alteplase and thrombectomy.
Successful reperfusion was less common in patients who had thrombectomy alone (91% vs. 96%; risk difference −5.1%; 95% confidence interval, −10.2 to 0.0, P = .047).
With combination therapy, more patients achieved functional independence with a modified Rankin scale score of 0-2 at 90 days (65% vs. 57%; adjusted risk difference −7.3%; 95% CI, −16·6 to 2·1, lower limit of one-sided 95% CI, −15·1%, crossing the noninferiority margin of −12%).
“Despite a very liberal noninferiority margin and strict inclusion and exclusion criteria aimed at studying a population most likely to benefit from thrombectomy alone, point estimates directionally favored intravenous thrombolysis plus thrombectomy,” Urs Fischer, MD, cochair of the Stroke Center, University Hospital Basel, Switzerland, told this news organization.
“Furthermore, we could demonstrate that overall reperfusion rates were extremely high and yet significantly better in patients receiving intravenous thrombolysis plus thrombectomy than in patients treated with thrombectomy alone, a finding which has not been shown before,” Dr. Fischer said.
There was no significant difference in the risk of symptomatic intracranial bleeding (3% with combination therapy and 2% with thrombectomy alone).
Based on the results, in patients suitable for thrombolysis, skipping it before thrombectomy “is not justified,” the study team concludes.
DIRECT-SAFE
DIRECT-SAFE enrolled 295 patients (median age 69; 43% women) with stroke and large vessel occlusion from Australia, New Zealand, China, and Vietnam, with half undergoing direct thrombectomy and half bridging therapy first.
Functional independence (modified Rankin Scale 0-2 or return to baseline at 90 days) was more common in the bridging group (61% vs. 55%).
Safety outcomes were similar between groups. Symptomatic intracerebral hemorrhage occurred in 2 (1%) patients in the direct group and 1 (1%) patient in the bridging group. There were 22 (15%) deaths in the direct group and 24 in the bridging group.
“There has been concern across the world regarding cost of treatment, together with fears of increasing bleeding risk or clot migration with intravenous thrombolytic,” lead investigator Peter Mitchell, MBBS, director, NeuroIntervention Service, The Royal Melbourne Hospital, Parkville, Victoria, Australia, told this news organization.
“We showed that patients in the bridging treatment arm had better outcomes across the entire study, especially in Asian region patients” and therefore remains “the gold standard,” Dr. Mitchell said.
To date, six published trials have addressed this question of endovascular therapy alone or with thrombolysis – SKIP, DIRECT-MT, MR CLEAN NO IV, SWIFT-DIRECT, and DIRECT-SAFE.
Dr. Fischer said the SWIFT-DIRECT study group plans to perform an individual participant data meta-analysis known as Improving Reperfusion Strategies in Ischemic Stroke (IRIS) of all six trials to see whether there are subgroups of patients in whom thrombectomy alone is as effective as thrombolysis plus thrombectomy.
Subgroups of interest, he said, include patients with early ischemic signs on imaging, those at increased risk for hemorrhagic complications, and patients with a high clot burden.
SWIFT-DIRECT was funding by Medtronic and University Hospital Bern. DIRECT-SAFE was funded by Australian National Health and Medical Research Council and Stryker USA. A complete list of author disclosures is available with the original articles.
A version of this article first appeared on Medscape.com.
Two new noninferiority trials address the controversial question of whether thrombolytic therapy can be omitted for acute ischemic stroke in patients undergoing endovascular thrombectomy for large-vessel occlusion.
Both trials show better outcomes when standard bridging thrombolytic therapy is used before thrombectomy, with comparable safety.
The results of SWIFT-DIRECT and DIRECT-SAFE were published online June 22 in The Lancet.
“The case appears closed. Bypass intravenous thrombolysis is highly unlikely to be noninferior to standard care by a clinically acceptable margin for most patients,” writes Pooja Khatri, MD, MSc, department of neurology, University of Cincinnati, in a linked comment.
SWIFT-DIRECT
SWIFT-DIRECT enrolled 408 patients (median age 72; 51% women) with acute stroke due to large vessel occlusion admitted to stroke centers in Europe and Canada. Half were randomly allocated to thrombectomy alone and half to intravenous alteplase and thrombectomy.
Successful reperfusion was less common in patients who had thrombectomy alone (91% vs. 96%; risk difference −5.1%; 95% confidence interval, −10.2 to 0.0, P = .047).
With combination therapy, more patients achieved functional independence with a modified Rankin scale score of 0-2 at 90 days (65% vs. 57%; adjusted risk difference −7.3%; 95% CI, −16·6 to 2·1, lower limit of one-sided 95% CI, −15·1%, crossing the noninferiority margin of −12%).
“Despite a very liberal noninferiority margin and strict inclusion and exclusion criteria aimed at studying a population most likely to benefit from thrombectomy alone, point estimates directionally favored intravenous thrombolysis plus thrombectomy,” Urs Fischer, MD, cochair of the Stroke Center, University Hospital Basel, Switzerland, told this news organization.
“Furthermore, we could demonstrate that overall reperfusion rates were extremely high and yet significantly better in patients receiving intravenous thrombolysis plus thrombectomy than in patients treated with thrombectomy alone, a finding which has not been shown before,” Dr. Fischer said.
There was no significant difference in the risk of symptomatic intracranial bleeding (3% with combination therapy and 2% with thrombectomy alone).
Based on the results, in patients suitable for thrombolysis, skipping it before thrombectomy “is not justified,” the study team concludes.
DIRECT-SAFE
DIRECT-SAFE enrolled 295 patients (median age 69; 43% women) with stroke and large vessel occlusion from Australia, New Zealand, China, and Vietnam, with half undergoing direct thrombectomy and half bridging therapy first.
Functional independence (modified Rankin Scale 0-2 or return to baseline at 90 days) was more common in the bridging group (61% vs. 55%).
Safety outcomes were similar between groups. Symptomatic intracerebral hemorrhage occurred in 2 (1%) patients in the direct group and 1 (1%) patient in the bridging group. There were 22 (15%) deaths in the direct group and 24 in the bridging group.
“There has been concern across the world regarding cost of treatment, together with fears of increasing bleeding risk or clot migration with intravenous thrombolytic,” lead investigator Peter Mitchell, MBBS, director, NeuroIntervention Service, The Royal Melbourne Hospital, Parkville, Victoria, Australia, told this news organization.
“We showed that patients in the bridging treatment arm had better outcomes across the entire study, especially in Asian region patients” and therefore remains “the gold standard,” Dr. Mitchell said.
To date, six published trials have addressed this question of endovascular therapy alone or with thrombolysis – SKIP, DIRECT-MT, MR CLEAN NO IV, SWIFT-DIRECT, and DIRECT-SAFE.
Dr. Fischer said the SWIFT-DIRECT study group plans to perform an individual participant data meta-analysis known as Improving Reperfusion Strategies in Ischemic Stroke (IRIS) of all six trials to see whether there are subgroups of patients in whom thrombectomy alone is as effective as thrombolysis plus thrombectomy.
Subgroups of interest, he said, include patients with early ischemic signs on imaging, those at increased risk for hemorrhagic complications, and patients with a high clot burden.
SWIFT-DIRECT was funding by Medtronic and University Hospital Bern. DIRECT-SAFE was funded by Australian National Health and Medical Research Council and Stryker USA. A complete list of author disclosures is available with the original articles.
A version of this article first appeared on Medscape.com.
Two new noninferiority trials address the controversial question of whether thrombolytic therapy can be omitted for acute ischemic stroke in patients undergoing endovascular thrombectomy for large-vessel occlusion.
Both trials show better outcomes when standard bridging thrombolytic therapy is used before thrombectomy, with comparable safety.
The results of SWIFT-DIRECT and DIRECT-SAFE were published online June 22 in The Lancet.
“The case appears closed. Bypass intravenous thrombolysis is highly unlikely to be noninferior to standard care by a clinically acceptable margin for most patients,” writes Pooja Khatri, MD, MSc, department of neurology, University of Cincinnati, in a linked comment.
SWIFT-DIRECT
SWIFT-DIRECT enrolled 408 patients (median age 72; 51% women) with acute stroke due to large vessel occlusion admitted to stroke centers in Europe and Canada. Half were randomly allocated to thrombectomy alone and half to intravenous alteplase and thrombectomy.
Successful reperfusion was less common in patients who had thrombectomy alone (91% vs. 96%; risk difference −5.1%; 95% confidence interval, −10.2 to 0.0, P = .047).
With combination therapy, more patients achieved functional independence with a modified Rankin scale score of 0-2 at 90 days (65% vs. 57%; adjusted risk difference −7.3%; 95% CI, −16·6 to 2·1, lower limit of one-sided 95% CI, −15·1%, crossing the noninferiority margin of −12%).
“Despite a very liberal noninferiority margin and strict inclusion and exclusion criteria aimed at studying a population most likely to benefit from thrombectomy alone, point estimates directionally favored intravenous thrombolysis plus thrombectomy,” Urs Fischer, MD, cochair of the Stroke Center, University Hospital Basel, Switzerland, told this news organization.
“Furthermore, we could demonstrate that overall reperfusion rates were extremely high and yet significantly better in patients receiving intravenous thrombolysis plus thrombectomy than in patients treated with thrombectomy alone, a finding which has not been shown before,” Dr. Fischer said.
There was no significant difference in the risk of symptomatic intracranial bleeding (3% with combination therapy and 2% with thrombectomy alone).
Based on the results, in patients suitable for thrombolysis, skipping it before thrombectomy “is not justified,” the study team concludes.
DIRECT-SAFE
DIRECT-SAFE enrolled 295 patients (median age 69; 43% women) with stroke and large vessel occlusion from Australia, New Zealand, China, and Vietnam, with half undergoing direct thrombectomy and half bridging therapy first.
Functional independence (modified Rankin Scale 0-2 or return to baseline at 90 days) was more common in the bridging group (61% vs. 55%).
Safety outcomes were similar between groups. Symptomatic intracerebral hemorrhage occurred in 2 (1%) patients in the direct group and 1 (1%) patient in the bridging group. There were 22 (15%) deaths in the direct group and 24 in the bridging group.
“There has been concern across the world regarding cost of treatment, together with fears of increasing bleeding risk or clot migration with intravenous thrombolytic,” lead investigator Peter Mitchell, MBBS, director, NeuroIntervention Service, The Royal Melbourne Hospital, Parkville, Victoria, Australia, told this news organization.
“We showed that patients in the bridging treatment arm had better outcomes across the entire study, especially in Asian region patients” and therefore remains “the gold standard,” Dr. Mitchell said.
To date, six published trials have addressed this question of endovascular therapy alone or with thrombolysis – SKIP, DIRECT-MT, MR CLEAN NO IV, SWIFT-DIRECT, and DIRECT-SAFE.
Dr. Fischer said the SWIFT-DIRECT study group plans to perform an individual participant data meta-analysis known as Improving Reperfusion Strategies in Ischemic Stroke (IRIS) of all six trials to see whether there are subgroups of patients in whom thrombectomy alone is as effective as thrombolysis plus thrombectomy.
Subgroups of interest, he said, include patients with early ischemic signs on imaging, those at increased risk for hemorrhagic complications, and patients with a high clot burden.
SWIFT-DIRECT was funding by Medtronic and University Hospital Bern. DIRECT-SAFE was funded by Australian National Health and Medical Research Council and Stryker USA. A complete list of author disclosures is available with the original articles.
A version of this article first appeared on Medscape.com.
FROM THE LANCET