• Opeolu Adeoye, Joseph Broderick, Colin P Derdeyn, James C Grotta, William Barsan, Oladi Bentho, Scott Berry, Mauricio Concha, Iris Davis, Stacie Demel, Jordan Elm, Nina Gentile, Todd Graves, Melissa Hoffman, Josephine Huang, James Ingles, Scott Janis, Adam S Jasne, Pooja Khatri, Steven R Levine, Aniel Majjhoo, Peter Panagos, Arthur Pancioli, Stephanie Pizzella, Tamra Ranasinghe, Noor Sabagha, Sanjeev Sivakumar, Christopher Streib, Achala Vagal, Alastair Wilson, Max Wintermark, Albert J Yoo, and Andrew D Barreto.
• From the Department of Emergency Medicine, Washington University, St. Louis (O.A., P.P., S.P.); the Departments of Neurology and Rehabilitation Medicine (J.B., I.D., S.D., M.H., P.K.), Emergency Medicine (A.P.), and Radiology (A.V.), University of Cincinnati, and the Department of Pharmacy, University of Cincinnati Medical Center (N.S.) - both in Cincinnati; the Department of Radiology, University of Virginia, Charlottesville (C.P.D.); the Clinical Institute for Research and Innovation, Memorial Hermann Hospital (J.C.G.), the Department of Neuroradiology, University of Texas M.D. Anderson Cancer Center (M.W.), and the Department of Neurology, University of Texas Health Science Center (A.D.B.), Houston, Berry Consultants, Austin (S.B., T.G.), and the Texas Stroke Institute, Medical City Healthcare, Dallas (A.J.Y.) - all in Texas; the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B.), and the Department of Neurology, McLaren Flint, Flint (A.M.) - both in Michigan; the Department of Neurology, University of Minnesota, Minneapolis (O.B., C.S.); the Department of Neurology, Sarasota Memorial Hospital, Intercoastal Medical Group, Sarasota (M.C.), and the Department of Neurology, Mayo Clinic, Jacksonville (J.H.) - both in Florida; the Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., J.I.), and the Department of Medicine (Neurology), Prisma Health-Upstate, University of South Carolina Greenville School of Medicine, Greenville (S.S.); the Department of Emergency Medicine, Temple University, Philadelphia (N.G.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (S.J.); the Department of Neurology, Yale University, New Haven, CT (A.S.J.); the Departments of Neurology and Emergency Medicine, State University of New York, New York (S.R.L.); the Department of Neurology, Wake Forest University, Winston-Salem, NC (T.R.); and the Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (A.W.).
• N. Engl. J. Med. 2024 Sep 5; 391 (9): 810820810-820.

BackgroundIntravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear.MethodsWe conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization.ResultsA total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%).ConclusionsIn patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).Copyright © 2024 Massachusetts Medical Society.

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