Oral anticoagulation with or without antiplatelet medication was found to increase the risk for bleeding, with minimal protective effect against ischemic stroke in patients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm, according to the results of a meta-analysis published in The American Journal of Cardiology.

Individuals with HFrEF are at greater risk for thrombotic events. Current guidelines for the management of patients with HFrEF in sinus rhythm remain unclear, with conflicting recommendations.

Investigators searched the PubMed and EMBASE databases through January 2020 to identify studies in which the safety and efficacy of a vitamin K antagonist (VKA) or direct oral anticoagulant (DOAC) was compared with that of an antiplatelet therapy or placebo in patients with HFrEF and normal sinus rhythm. A total of 5 randomized controlled trials (n=9390; age range, 59-67 years; 74%-85% men; left ventricular ejection fraction range, 24%-35%) were identified and included in the qualitative synthesis and network meta-analysis.

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These patients were randomly assigned to receive VKA (n=1883), low dose rivaroxaban 2.5 mg twice a day (n=2507), antiplatelet therapy (n=4877), or placebo (n=143). The primary efficacy outcome was the incidence of major adverse cardiovascular events (MACE; ie, myocardial infarction, stroke, rehospitalization for heart failure, and all-cause mortality). The primary safety outcome was the incidence of major bleeding. Mean follow-up duration of studies examined ranged from 19 to 42 months.

The occurrence of stroke was not reduced by treatment with VKW or rivaroxaban compared with placebo, and these medications were associated with elevated greater risk for major bleeding (respective relative risks [RRs]: VKA, 8.62; 95% CI, 1.52-48.9; rivaroxaban, 6.86; 95% CI, 1.16-40.7).

Both VKA (RR, 0.50; 95% CI, 0.33-0.76) and rivaroxaban (RR, 0.67; 95% CI, 0.47-0.96) were associated with a reduced risk for stroke compared with antiplatelet medications, and increased risks for major bleeding (VKA: RR, 2.07; 95% CI, 1.51-2.84; rivaroxaban: RR, 1.65; 95% CI, 1.16-2.33).

Incidences of stroke and major bleeding were comparable for VKA vs rivaroxaban, and for antiplatelet therapy vs placebo. The incidence of myocardial infarction, rehospitalization, or all-cause mortality were comparable for all treatments.

Study limitations include heterogeneity in inclusion and exclusion criteria and antithrombotic therapy dosages between trials, the diversity in antiplatelet medications examined, and the inclusion of participants with prior atrial fibrillation in some trials.

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“Our study does not support the use of low dose rivaroxaban or VKA in patients with HFrEF and sinus rhythm whom otherwise do not require anticoagulation,” noted the authors. “Our study does not support the use of antiplatelet agents in HFrEF and sinus rhythm in the absence of an independent indication.”


Ueyama H, Takagi H, Briasoulis A, Harrington M, Steinberg D, Kuno T. Meta-analysis of antithrombotic strategies in patients with heart failure with reduced ejection fraction and sinus rhythm. Am J Cardiol. April 2020. doi:10.1016/j.amjcard.2020.04.007