You still have the wrong fucking endpoint for your research. Reperfusion means nothing to survivors, 100% RECOVERY IS THE ONLY GOAL IN STROKE. WHEN THE HELL WILL YOU DO YOUR FUCKING RESEARCH CORRECTLY?
Off-Label Thrombolytic Could 'Rescue' Stroke Thrombectomy
Registry results are promising for urokinase
Intra-arterial urokinase may safely
boost reperfusion when mechanical thrombectomy misses the mark for large
vessel anterior circulation stroke, an observational study suggested.
The most feared complication -- symptomatic intracranial hemorrhage (sICH) -- was actually numerically less common for patients who got the drug off label for no or incomplete flow after mechanical thrombectomy (5.2% vs 6.9%), with an odds ratio of 0.81 after adjustment for baseline characteristics underlying case selection (95% CI 0.31-2.13).
Likewise,
secondary endpoints at least tended to favor urokinase in the
prospective registry of consecutive patients, reported Urs Fischer, MD,
of University Hospital Bern, Switzerland, and colleagues in JAMA Neurology:
This study moves the field one step closer to one of the primary targets for improving thrombectomy -- "finding reliable means of achieving near-perfect perfusion," wrote Victor Lopez-Rivera, MD, and Sunil Sheth, MD, both of the UTHealth McGovern Medical School in Houston, in an accompanying editorial.
Better reperfusion has translated to better outcomes in prior studies, but only a minority of thrombectomy patients reach the highest Thrombolysis in Cerebral Infarction (TICI) grades of reperfusion, they pointed out.
"There remain occlusions that require multiple passes, some that fragment and travel downstream to occlude distal vessels that are less amenable to mechanical approaches, and still some that, despite multiple attempts, refuse to be removed," the editorialists wrote.
The low hemorrhage rate was remarkable given the history of recombinant prourokinase being denied FDA approval based on a 10% rate of symptomatic hemorrhage, they added.
The
researchers called for systemic evaluation of this approach in a
multicenter prospective registry or a randomized clinical trial.
Despite limitations as an observational study prone to bias, "the fact that the ICH rate remained comparable to those presented in numerous other studies of MT [mechanical thrombectomy] alone (without additional intra-arterial thrombolysis), as well as those of intravenous thrombolysis alone, speaks to the real possibility of safety for concomitant antithrombotics with MT beyond intravenous alteplase [Activase]," Lopez-Rivera and Sheth wrote.
Urokinase was approved for lysis of pulmonary emboli in adults, but the Kinlytic brand is off the U.S. market, where alteplase is the only approved stroke thrombolytic available.
The study utilized the prospective registry of a tertiary care stroke center to include 993 consecutive participants treated with second-generation mechanical thrombectomy from Jan. 1, 2010 through Aug. 4, 2017 who met criteria for a large vessel occlusion in the anterior circulation and agreed to participate.
Among them, 10.1% got additional intra-arterial urokinase, typically for incomplete reperfusion after thrombectomy (53 of 100).
In
those cases with less than TICI grade 3 flow, urokinase was associated
with an early improvement in reperfusion for 32 (60.4%), and 18 (34.0%)
had an improvement in TICI grade.
"This finding then begs the question of whether concomitant thrombolysis in patients with [large vessel occlusions] is in fact beneficial," the editorialists wrote.
They pointed to the SWIFT-DIRECT trial randomizing large vessel occlusion patients to mechanical thrombectomy with or without IV alteplase.
The most feared complication -- symptomatic intracranial hemorrhage (sICH) -- was actually numerically less common for patients who got the drug off label for no or incomplete flow after mechanical thrombectomy (5.2% vs 6.9%), with an odds ratio of 0.81 after adjustment for baseline characteristics underlying case selection (95% CI 0.31-2.13).
- 90-day mortality: adjusted OR 0.78 (95% CI 0.43-1.40)
- 90-day functional independence: aOR 1.93 (95% CI 1.11-3.37)
This study moves the field one step closer to one of the primary targets for improving thrombectomy -- "finding reliable means of achieving near-perfect perfusion," wrote Victor Lopez-Rivera, MD, and Sunil Sheth, MD, both of the UTHealth McGovern Medical School in Houston, in an accompanying editorial.
Better reperfusion has translated to better outcomes in prior studies, but only a minority of thrombectomy patients reach the highest Thrombolysis in Cerebral Infarction (TICI) grades of reperfusion, they pointed out.
"There remain occlusions that require multiple passes, some that fragment and travel downstream to occlude distal vessels that are less amenable to mechanical approaches, and still some that, despite multiple attempts, refuse to be removed," the editorialists wrote.
The low hemorrhage rate was remarkable given the history of recombinant prourokinase being denied FDA approval based on a 10% rate of symptomatic hemorrhage, they added.
Despite limitations as an observational study prone to bias, "the fact that the ICH rate remained comparable to those presented in numerous other studies of MT [mechanical thrombectomy] alone (without additional intra-arterial thrombolysis), as well as those of intravenous thrombolysis alone, speaks to the real possibility of safety for concomitant antithrombotics with MT beyond intravenous alteplase [Activase]," Lopez-Rivera and Sheth wrote.
Urokinase was approved for lysis of pulmonary emboli in adults, but the Kinlytic brand is off the U.S. market, where alteplase is the only approved stroke thrombolytic available.
The study utilized the prospective registry of a tertiary care stroke center to include 993 consecutive participants treated with second-generation mechanical thrombectomy from Jan. 1, 2010 through Aug. 4, 2017 who met criteria for a large vessel occlusion in the anterior circulation and agreed to participate.
Among them, 10.1% got additional intra-arterial urokinase, typically for incomplete reperfusion after thrombectomy (53 of 100).
"This finding then begs the question of whether concomitant thrombolysis in patients with [large vessel occlusions] is in fact beneficial," the editorialists wrote.
They pointed to the SWIFT-DIRECT trial randomizing large vessel occlusion patients to mechanical thrombectomy with or without IV alteplase.
The study was supported by the Swiss Stroke Society, the Bangerter Foundation, and the Swiss Academy of Medical Sciences.
Fischer disclosed relevant relationships with Medtronic, Stryker, and CSL Behring.
Sheth disclosed an award from the American Academy of Neurology and a grant from the NIH.
Lopez-Rivera disclosed no relevant relationships with industry.
Fischer disclosed relevant relationships with Medtronic, Stryker, and CSL Behring.
Sheth disclosed an award from the American Academy of Neurology and a grant from the NIH.
Lopez-Rivera disclosed no relevant relationships with industry.
last updated
Primary Source
JAMA Neurology
Source Reference: Kaesmacher J, et al "Safety and efficacy of intra-arterial urokinase after failed, unsuccessful, or incomplete mechanical thrombectomy in anterior circulation large-vessel occlusion stroke" JAMA Neurol 2019; DOI: 10.1001/jamaneurol.2019.4192.Secondary Source
JAMA Neurology
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