Did the addition of low-dose rivaroxaban to background antiplatelet therapy reduce risk for thromboembolic events in patients with chronic heart failure and reduced ejection fraction, coronary artery disease, and sinus rhythm?
In this post hoc analysis of a randomized clinical trial of 5022 patients, although thromboembolic events were not the major driver of the primary efficacy outcome, they occurred frequently. Rivaroxaban was associated with reduced risk of thromboembolic events compared with placebo from 15.5% to 13.1% with inclusion of sudden/unwitnessed deaths as part of the outcome and from 7.6% to 6.1% when sudden/unwitnessed deaths where not considered as part of the thromboembolic composite outcome.
Thromboembolic events are common in patients with heart failure, coronary artery disease, and sinus rhythm, and rivaroxaban may reduce risk of their occurrence.
Whether 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.
To examine whether low-dose rivaroxaban was associated with reduced thromboembolic events in patients enrolled in the COMMANDER HF trial.
Design, Setting, and Participants
Post 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.
Patients 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 Measures
For 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.
Of 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 Relevance
In 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.
ClinicalTrials.gov identifier: NCT01877915
Greenberg B, Neaton JD, Anker SD, et al. Association of Rivaroxaban With Thromboembolic Events in Patients With Heart Failure, Coronary Disease, and Sinus Rhythm: A Post Hoc Analysis of the COMMANDER HF Trial. JAMA Cardiol. Published online April 24, 20194(6):515–523. doi:10.1001/jamacardio.2019.1049
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