• Barry Greenberg, James D Neaton, Stefan D Anker, William M Byra, ClelandJohn G FJGFRobertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow, Scotland.National Heart and Lung Institute, Imperial College London, London, England., Hsiaowei Deng, Min Fu, David A La Police, LamCarolyn S PCSPNational Heart Centre Singapore, Singapore.Duke-National University of Singapore, Singapore.Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Mandeep R Mehra, Christopher C Nessel, Theodore E Spiro, Dirk J van Veldhuisen, Catherine M Vanden Boom, and Faiez Zannad.
• Cardiology Division, Department of Medicine, University of California, San Diego, La Jolla.
• JAMA Cardiol. 2019 Jun 1; 4 (6): 515-523.

ImportanceWhether anticoagulation benefits patients with heart failure (HF) in sinus rhythm is uncertain. The COMMANDER HF randomized clinical trial evaluated the effects of adding low-dose rivaroxaban to antiplatelet therapy in patients with recent worsening of chronic HF with reduced ejection fraction, coronary artery disease (CAD), and sinus rhythm. Although the primary end point of all-cause mortality, myocardial infarction, or stroke did not differ between rivaroxaban and placebo, there were numerical advantages favoring rivaroxaban for myocardial infarction and stroke.ObjectiveTo examine whether low-dose rivaroxaban was associated with reduced thromboembolic events in patients enrolled in the COMMANDER HF trial.Design, Setting, And ParticipantsPost hoc analysis of the COMMANDER HF multicenter, randomized, double-blind, placebo-controlled trial in patients with CAD and worsening HF. The trial randomized 5022 patients postdischarge from a hospital or outpatient clinic after treatment for worsening HF between September 2013 and October 2017. Patients were required to be receiving standard care for HF and CAD and were excluded for a medical condition requiring anticoagulation or a bleeding history. Patients were randomized in a 1:1 ratio. Analysis was conducted from June 2018 and January 2019.InterventionPatients were randomly assigned to receive 2.5 mg of rivaroxaban given orally twice daily or placebo in addition to their standard therapy.Main Outcomes And MeasuresFor this post hoc analysis, a thromboembolic composite was defined as either (1) myocardial infarction, ischemic stroke, sudden/unwitnessed death, symptomatic pulmonary embolism, or symptomatic deep venous thrombosis or (2) all of the previous components except sudden/unwitnessed deaths because not all of these are caused by thromboembolic events.ResultsOf 5022 patients, 3872 (77.1%) were men, and the overall mean (SD) age was 66.4 (10.2) years. Over a median (interquartile range) follow-up of 19.6 (11.7-30.8) months, fewer patients assigned to rivaroxaban compared with placebo had a thromboembolic event including sudden/unwitnessed deaths: 328 (13.1%) vs 390 (15.5%) (hazard ratio, 0.83; 95% CI, 0.72-0.96; P = .01). When sudden/unwitnessed deaths were excluded, the results analyzing thromboembolic events were similar: 153 (6.1%) vs 190 patients (7.6%) with an event (hazard ratio, 0.80; 95% CI, 0.64-0.98; P = .04).Conclusions And RelevanceIn this study, thromboembolic events occurred frequently in patients with HF, CAD, and sinus rhythm. Rivaroxaban may reduce the risk of thromboembolic events in this population, but these events are not the major cause of morbidity and mortality in patients with recent worsening of HF for which rivaroxaban had no effect. While consistent with other studies, these results require confirmation in prospective randomized clinical trials.Trial RegistrationClinicalTrials.gov identifier: NCT01877915.

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