Clinical question: Does rivaroxaban prevent recurrent ischemic stroke in patients with embolic stroke from undetermined source?
Background: Embolic stroke of undetermined source (ESUS) represents approximately 20% of ischemic strokes. Rivaroxaban inhibits factor Xa and is shown to be effective for secondary stroke prevention in patients with nonvalvular atrial fibrillation. Strategies to prevent cryptogenic stroke caused by mechanisms other than cardioembolic sources are lacking.
Study design: International, double-blind, event-driven, randomized, phase III trial.
Setting: 459 hospitals in 31 countries, during 2014-2017.
Synopsis: 7,213 patients with ESUS were randomized to receive either 15 mg of rivaroxaban once daily or aspirin 100 mg once daily. The primary outcome was established as the first recurrent stroke of any type or systemic embolism. The primary safety endpoint was major bleeding.
Recurrent stroke was observed in 158 in the rivaroxaban group and 156 in the aspirin group, mostly ischemic. The trial was terminated early because of a higher incidence of intracranial hemorrhage and major bleeding among patients assigned to rivaroxaban at an annual rate of 1.8%, compared with 0.7% (hazard ratio, 2.72; 95% confidence interval, 1.68-4.39; P less than .001). Although the study utilized strict criteria to define ESUS, it is feasible that the lack of benefit may be due to heterogeneous arterial, cardiogenic, and paradoxical emboli with diverse composition and poor response to rivaroxaban.
Bottom line: Rivaroxaban does not confer protection from recurrent stroke in patients with embolic stroke of unknown origin and increases risk for intracranial hemorrhage and major bleeding.
Citation: Hart RG et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-201.
Dr. Vela-Duarte is assistant professor of neurology at the University of Colorado, Denver