Key messages
– For people who have heart failure with a normal heart rhythm, there seems to be little to no advantage of warfarin (an anticoagulant: a medicine which prevents blood clotting by blocking proteins) over antiplatelet medicines like aspirin (which prevent blood clotting by blocking platelets).
– Treatment with warfarin leads to more bleeding problems than aspirin or clopidogrel.
How do anticoagulant and antiplatelet treatments help people with heart failure?
Some people with heart failure have an abnormal heart rhythm (known as atrial fibrillation) but some have a normal heart rhythm (known as sinus rhythm). People with heart failure might have slower blood flow in the heart, which puts them at risk of blood clots forming. Blood clots can be formed by clotting proteins (coagulation factors) and sticky blood cells (platelets).
Many people who have heart failure with normal rhythm have narrowed heart arteries, and doctors often give them aspirin, which is a medicine that can reduce clotting by blocking platelets. People with heart failure are also at risk of blood clots (thromboembolism) in the lungs, legs and brain (ischaemic stroke), which can lead to disability and death.
Oral anticoagulation (OAC) medicines like warfarin can block clotting proteins and help to prevent blood clots from forming. Warfarin is known to be better than aspirin for people with heart failure who have abnormal heart rhythm, so several studies have tried to find out whether all people with heart failure (including those with normal heart rhythm) should receive OAC.
What did we want to find out?
We wanted to find out whether there was any difference between the effects of anticoagulants and antiplatelets for people with heart failure and normal heart rhythm. In particular, we wanted to know if the type of medicine made any difference to the risk of dying, clotting complications (e.g. a heart attack or stroke), or serious bleeding problems.
What did we do?
We looked for studies that gave at least a month of antiplatelet or anticoagulant medicines to adults with heart failure in normal rhythm, with the type of treatment chosen at random. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We included four studies which treated a total of 4187 people.
We found that the risk of dying was almost identical whether people in the four studies took aspirin or warfarin. There was not enough evidence to prove the benefits of warfarin over aspirin to reduce the possibility of clotting complications, such as a heart attack or stroke. However, people receiving warfarin experienced serious bleeding twice as often as those taking aspirin. One medium-sized study also compared warfarin with another antiplatelet drug, clopidogrel, and showed similar results: no difference in occurrence of death or clotting complications, but a higher chance of developing a serious bleed.
It is unlikely that further studies will change these conclusions unless new, more effective and safe drugs become available.
What are the limitations of the evidence?
We are only moderately confident in the evidence comparing warfarin with aspirin because there were few cases of clotting complications and bleeding, and because there were not enough studies to be certain about the risk of dying.
We have little confidence in the evidence comparing warfarin with clopidogrel because the evidence was based on only a few cases and there were not enough studies to be certain about the findings.
How up to date is this evidence?
This is an update of an earlier review. The evidence is current to April 2025.
閱讀完整摘要
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 strategy
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.
