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. 2025 Aug 18:e252794.
doi: 10.1001/jamaneurol.2025.2794. Online ahead of print.

Intravenous Argatroban or Eptifibatide in Patients Undergoing Mechanical Thrombectomy: A Subgroup Analysis of the MOST Randomized Clinical Trial

Ian Rines  1 , Opeolu Adeoye  2 , Andrew D Barreto  3 , Joseph Broderick  4 , Janice Carrozzella  5 , Hui Chen  6 , Mauricio Concha  7 , Jordan Elm  1 , James C Grotta  8 , Adam S Jasne  9 , Pooja Khatri  4 , Akash Roy  1 , Achala Vagal  5 , Max Wintermark  6 , Albert J Yoo  10 , Colin P Derdeyn  11 ; MOST Investigators
Collaborators, Affiliations

Intravenous Argatroban or Eptifibatide in Patients Undergoing Mechanical Thrombectomy: A Subgroup Analysis of the MOST Randomized Clinical Trial

Ian Rines et al. JAMA Neurol. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Adeoye reported receiving grants from National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) and equity from Sense Diagnostics outside the submitted work. Dr Broderick reported receiving consulting fees from Roche-Genentech, Brainsgate, and Basking Bioscience; study medication and financial support from Novo Nordisk; and personal fees from Kroger Prescription Plans for serving on the pharmacy and therapeutics committee outside the submitted work. Dr Carrozzella reported receiving salary support from the University of Cincinnati during the conduct of the study. Dr Concha reported receiving payments for protocol activities from the NIH during the conduct of the study and personal fees as medical director of Sarasota Memorial HealthCare System for the Comprehensive Stroke Center outside the submitted work. Dr Elm reported grants from NINDS during the conduct of the study. Dr Khatri reported receiving grants from Cerenovus and scientific advisor fees from Lumosa and Basking Biosciences outside the submitted work. Dr Vagal reported receiving consulting fees from Cerebra AI and grants from NIH/NINDS Imaging core lab outside the submitted work. Dr Yoo reported receiving personal fees from NIH/NINDS as endovascular safety monitor during the conduct of the study; grants from Medtronic, Cerenovus, Penumbra, Stryker, and Genentech; consultant fees from Cerenovus, Penumbra, Vesalio, Rapid Medical; nonfinancial support as consultant from Nicolab and Zoll Circulation outside the submitted work; and equity interest in Insera Therapeutics, Galaxy Therapeutics, and Gravity Medical. Dr Derdeyn reported receiving personal/data safety monitoring board fees from Penumbra, THUNDER and MIND Trials, Silk Road, NITE trial, and Basking Neurosciences, RAISE trial outside the submitted work. No other disclosures were reported.

References

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