Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source

Abstract

Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding. (Funded by Bayer and Janssen Research and Development; NAVIGATE ESUS ClinicalTrials.gov number, NCT02313909 .).

Secondary prevention of ischaemic stroke

“…In two recent large multicentre randomised controlled trials of patients with ESUS, anticoagulation was not superior to aspirin with respect to secondary ischaemic stroke prevention. 3,14 NAVIGATE ESUS 14 compared rivaroxaban 15 mg daily and aspirin 100 mg daily. The trial was terminated early by the data and safety monitoring committee, following the recruitment of 7213 patients, due to an excess risk of major bleeding with rivaroxaban (HR 2.72; 95% CI 1.68-4.39, P < 0.001), with no significant decrease in the risk of recurrent stroke (HR 1.07; 95% CI 0.87-1.33).…”

Higher bleeding rates in patients taking rivaroxaban following an embolic stroke of undetermined source

“…The authors stated that the use of antiplatelets or anticoagulants 'for a specific indication' was an exclusion criterion. 2 However, it is notable that 17% of the patients included in each arm were on aspirin before the qualifying stroke. There is no mention of the aspirin dose or whether it had been discontinued prior to trial participation.…”

“…5 However, the higher bleeding risk remains, especially when compared with rates of bleeding on a single agent from either drug family. 2,5,6 Therefore, it is conceivable that the combination of aspirin and rivaroxaban could have, at least in part, contributed to the higher rate of bleeding events observed in the NAVI-GATE ESUS trial. 2 Given the associated risks of combination therapy, clinicians and pharmacists ought to exercise diligence when prescribing for and reviewing medications of these patients.…”

Odyssey of Patent Foramen Ovale: Closure in Cryptogenic Stroke: The Canary in the Coal Mine of Clinical Trials?

“…Because this aspect was not the primary focus of their analysis, the authors did not apply the trial sequential analysis framework to this question to assess the adequacy of the available sample size, and 353 patients available in the present study to answer this question is likely insufficient. The NAVIGATE ESUS (Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source) trial comparing rivaroxaban versus aspirin for the prevention of stroke and systemic embolism after cryptogenic stroke was stopped early for futility with an excess of bleeding and no difference in efficacy versus aspirin—questions remain regarding the appropriateness of the trialed dose (15 mg daily) 12. The ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke) trial (NCT03192215) will test the impact of apixaban on stroke recurrence among patients with cryptogenic stroke and atrial cardiopathy.…”