Abstract
IMPORTANCE: The addition of direct thrombin inhibitors or glycoprotein platelet inhibitors to intravenous thrombolysis in patients undergoing endovascular thrombectomy for acute ischemic stroke may improve reperfusion rates and clinical outcomes. OBJECTIVE: To investigate the safety and efficacy of these agents. DESIGN, SETTING, AND PARTICIPANTS: This was a preplanned cohort analysis from the Multi-Arm Optimization of Stroke Thrombolysis (MOST) randomized clinical trial, which lasted from 2019 to 2023 with a 90-day follow-up. Centrally read outcomes were assessed blinded to treatment. The MOST study was a multicenter, multiarm, adaptive, single-blind, phase 3 trial that included patients with acute ischemic stroke who were selected for thrombectomy per standard of care. INTERVENTIONS: Patients were randomized to placebo, argatroban, or eptifibatide within 75 minutes of intravenous thrombolysis. MAIN OUTCOMES AND MEASURES: The 90-day utility-weighted modified Rankin Scale (UW-mRS) score (range, 0-10, with higher scores reflecting better outcomes) was used as the primary outcome measure. Reperfusion rates and safety (hemorrhage rates) were also assessed, where good reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b/2c/3 on the completion angiogram. RESULTS: A total of 5376 patients were assessed for eligibility. Of these individuals, 4332 did not meet inclusion criteria, 251 eligible patients did not have consent obtained, 279 were excluded for other reasons, and 514 were randomized in the MOST trial. A total of 254 were planned for thrombectomy (110 in the placebo group, 31 in the argatroban group, and 113 in the eptifibatide group). Mean (SD) age was 68 (14.3) years, and 134 (53%) were female. Of these patients, 219 received thrombectomy: 94 in the placebo group, 27 in the argatroban group, and 98 in the eptifibatide group. There was no effect of treatment on outcome (mean UW-mRS score: eptifibatide, 6.47; 95% CI, 5.79-7.15; argatroban, 5.35; 95% CI, 4.13-6.58; placebo, 6.68; 95% CI, 5.98-7.39). Rates of good reperfusion were similar between groups (83 of 92 in the placebo group [83%]; 17 of 27 in the argatroban group [63%], and 82 of 98 in the eptifibatide group [84%]). The proportion of symptomatic intracranial hemorrhage was similar between groups. CONCLUSIONS AND RELEVANCE: Results of this secondary analysis of the MOST randomized clinical trial reveal that the addition of argatroban or eptifibatide to intravenous thrombolysis was not associated with better reperfusion rates or clinical outcomes in patients undergoing endovascular thrombectomy. Future investigations of these agents as intravenous adjuncts to thrombectomy should focus on populations who are ineligible for intravenous thrombolysis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03735979.