TY - JOUR
T1 - Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke
AU - Adeoye, O.
AU - Broderick, J.
AU - Derdeyn, C. P.
AU - Grotta, J. C.
AU - Barsan, W.
AU - Bentho, O.
AU - Berry, S.
AU - Concha, M.
AU - Davis, I.
AU - Demel, S.
AU - Elm, J.
AU - Gentile, N.
AU - Graves, T.
AU - Hoffman, M.
AU - Huang, J.
AU - Ingles, J.
AU - Janis, S.
AU - Jasne, A. S.
AU - Khatri, P.
AU - Levine, S. R.
AU - Majjhoo, A.
AU - Panagos, P.
AU - Pancioli, A.
AU - Pizzella, S.
AU - Ranasinghe, T.
AU - Sabagha, N.
AU - Sivakumar, S.
AU - Streib, C.
AU - Vagal, A.
AU - Wilson, A.
AU - Wintermark, M.
AU - Yoo, A. J.
AU - Barreto, A. D.
N1 - Publisher Copyright:
Copyright © 2024 Massachusetts Medical Society.
PY - 2024/9/5
Y1 - 2024/9/5
N2 - BACKGROUND Intravenous 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. METHODS We 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. RESULTS A 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%). CONCLUSIONS In 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.
AB - BACKGROUND Intravenous 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. METHODS We 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. RESULTS A 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%). CONCLUSIONS In 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.
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U2 - 10.1056/nejmoa2314779
DO - 10.1056/nejmoa2314779
M3 - Article
C2 - 39231343
AN - SCOPUS:85203319198
SN - 0028-4793
VL - 391
SP - 810
EP - 820
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 9
ER -