Antiplatelet versus anticoagulation treatment for people with heart failure in sinus rhythm.

Background: People with chronic heart failure have an increased risk of thrombotic complications, including stroke and thromboembolism, which in turn contribute to high mortality. Oral anticoagulants (e.g. warfarin) and antiplatelet agents (e.g. aspirin) are the principal oral antithrombotic agents. Many people with heart failure in sinus rhythm take aspirin because coronary artery disease is the leading cause of heart failure. Oral anticoagulation (OAC) has become a standard in the management of heart failure with atrial fibrillation. However, uncertainty regarding the appropriateness of OAC in heart failure with sinus rhythm remains. This is an update of a review previously published in 2016.

Objectives: To assess the effects of OAC versus antiplatelet agents for all-cause mortality, non-fatal cardiovascular events and risk of major bleeding in adults with heart failure (either with reduced or preserved ejection fraction) who are in sinus rhythm.

Search methods: In April 2025, we updated the searches of CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) portal. We searched the reference lists of papers and abstracts from cardiology meetings and contacted study authors for further information. We did not apply any language restrictions.

Selection criteria: We included randomised controlled trials (RCTs) comparing antiplatelet therapy versus OAC in adults with chronic heart failure in sinus rhythm. Treatment had to last for at least one month. We compared oral antiplatelets (aspirin, ticlopidine, clopidogrel, prasugrel, ticagrelor, dipyridamole) versus OAC (coumarins, warfarin, non-vitamin K oral anticoagulants).

Data collection and analysis: Three review authors independently assessed trials for inclusion and assessed the benefits and harms of antiplatelet therapy versus OAC by calculating risk ratios (RRs) with 95% confidence intervals (CIs). We used GRADE criteria to assess the certainty of evidence.

Main results: This update did not identify additional studies for inclusion, so the evidence base remains unchanged since the previous review version (published in 2016). We included four RCTs with 4187 eligible participants. All studies compared warfarin with aspirin. One RCT additionally compared warfarin with clopidogrel. All included RCTs studied people with heart failure with reduced ejection fraction. Analysis of all outcomes for warfarin versus aspirin was based on 3663 participants from four RCTs. Warfarin and aspirin probably both reduce all-cause mortality, with little to no difference between their risks: 21.9% for warfarin, 21.9% for aspirin (RR 1.00, 95% CI 0.89 to 1.13; 4 studies, 3663 participants; moderate-certainty evidence). OAC probably reduces the risk of non-fatal cardiovascular events (6.6% for warfarin, 8.3% for aspirin), which included non-fatal stroke, myocardial infarction, pulmonary embolism, peripheral arterial embolism (RR 0.79, 95% CI 0.63 to 1.00; 4 studies, 3663 participants; moderate-certainty evidence). Warfarin probably increases the risk of major bleeding events: 5.6% for warfarin, 2.8% for aspirin (RR 2.00, 95% CI 1.44 to 2.78; 4 studies, 3663 participants; moderate-certainty evidence). We considered the risk of bias of the included studies to be low. Analysis of warfarin versus clopidogrel was based on one RCT (N = 1064). With little to no difference between their risks, warfarin and clopidogrel may both reduce all-cause mortality: 17.0% for warfarin, 18.3% for clopidogrel (RR 0.93, 95% CI 0.72 to 1.21; 1 study, 1064 participants; low-certainty evidence) and non-fatal cardiovascular events slightly, 4.6% for warfarin, 5.4% for clopidogrel (RR 0.85, 95% CI 0.50 to 1.45; 1 study, 1064 participants; low-certainty evidence). Warfarin may increase the risk of major bleeding events slightly: 4.9% for warfarin, 2.0% for clopidogrel (RR 2.47, 95% CI 1.24 to 4.91; 1 study, 1064 participants; low-certainty evidence). We considered the risk of bias for this to be low.

Authors' conclusions: There is some evidence from RCTs that OAC with warfarin compared to platelet inhibition with aspirin probably has little to no effect on mortality in people with systolic heart failure in sinus rhythm (moderate-certainty evidence). Treatment with warfarin probably reduces non-fatal cardiovascular events but probably increases the risk of major bleeding complications (moderate-certainty evidence). We saw a similar pattern of results for the warfarin versus clopidogrel comparison (low-certainty evidence). At present, there are no data on the role of OAC versus antiplatelet agents in heart failure with preserved ejection fraction in sinus rhythm. Also, there were no data from RCTs on the utility of non-vitamin K antagonist oral anticoagulants compared to antiplatelet agents in heart failure with sinus rhythm.