Navigating Major Bleeding and Embolic Strokes of Undetermined Source
Kevin O’Connor, MD
Mikulík R, Eckstein J, Pearce LA, Mundl H, Rudilosso S, Olavarría VV, Shoamanesh A, Chamorro Á, Martí-Fàbregas J, Veltkamp R, et al. Frequency and Predictors of Major Bleeding in Patients With Embolic Strokes of Undetermined Source: NAVIGATE-ESUS Trial. Stroke. 2020;51:2139-2147.
About a third of ischemic strokes are categorized as being cryptogenic. Embolic strokes of unknown source (ESUS) represent a subset of these cryptogenic strokes. Clinicians are often faced with choosing between an anticoagulant and a platelet antiaggregant as one component of secondary prevention in patients having an ESUS. The NAVIGATE-ESUS trial provides data on the frequency and predictors of major bleeding in ESUS patients based on antithrombotic therapy choice, which can help inform treatment decisions.
NAVIGATE-ESUS was an international, double-blind, phase III trial that included 7213 participants from 31 countries who were randomized to receive rivaroxaban 15 mg once daily or aspirin 100 mg once daily. Sites were in Europe, East Asia, North America, and Latin America. The primary outcome of this analysis was major bleeding. Clinically-relevant nonmajor bleeding (CRNMB) was excluded for several reasons: CRNMB determinations were not determined centrally, whereas there was centralized adjudication of major bleeding events; intracranial bleeding was not considered to be a CRNMB; and analysis of independent predictors of major bleeding and CRNMBs such as epistaxis requiring medical attention would have been potentially spurious. NAVIGATE-ESUS was terminated before targeted enrollment was completed after an interim analysis found increased bleeding among rivaroxaban-treated participants, but no reduction in recurrent stroke.