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Alteplase after mechanical thrombectomy improves stroke outcomes

Journal
JAMA
Reuters Health - 15/02/2022 - For patients with large-vessel-occlusion stroke, intra-arterial thrombolysis following successful thrombectomy improves neurological outcomes, according to results of the CHOICE randomized controlled trial. 

"It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days," Dr. Angel Chamorro of Hospital Clinic of Barcelona in Spain and colleagues note in their paper. 

The placebo-controlled CHOICE study evaluated the efficacy and safety of adjunct intra-arterial alteplase following angiographically successful mechanical thrombectomy in patients with large-vessel-occlusion acute ischemic stroke. It was published in JAMA and simultaneously reported at the International Stroke Conference. 

The findings are based on 61 patients who received intra-arterial alteplase infusion for 15 to 30 minutes at a dose of 0.225 mg/kg (maximum dose, 22.5 mg) and 52 who received intra-arterial placebo infusion. 

Significantly more patients who received alteplase than placebo had an "excellent" neurological outcome at 90 days, defined as a modified Rankin Scale score of 0 or 1 (59.0% vs. 40.4%; adjusted risk difference, 18.4%; 95% CI, 0.3% to 36.4%; P=0.047). 

The benefit with alteplase was not associated with an increased rate of symptomatic or asymptomatic intracranial hemorrhage at 24 hours or mortality at 90 days. 

"Adjunct administration of intra-arterial alteplase at the end of the endovascular procedure resulted in improved clinical outcome despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging. This suggests that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion," the researchers write. 

They caution that the CHOICE trial was stopped prematurely because of slow recruitment and an inability to maintain the supply of placebo during the COVID-19 pandemic. The early termination could overestimate the treatment effect. The small sample size is another limitation. 

Given the limitations of the study, the authors say the CHOICE findings "should be interpreted as preliminary until replicated." 

In a JAMA editorial, Dr. Pooja Khatri of the University of Cincinnati, Ohio, says the findings suggest that "additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses." 

"This approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients, and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach. Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed," Dr. Khatri concludes. 

The study was supported by Fundacio La Marato de TV3 and by the Spanish Ministry of Health. Study medication and placebo were provided by Boehringer Ingelheim. Dr. Chamorro reported a patent pending with FreeOx Biotech. 

SOURCE: https://bit.ly/3gExTUL and https://bit.ly/3HJl9rZ  JAMA, online February 10, 2022. 

By Reuters Staff 



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