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Meta-Analysis
. 2014 Mar 28;2014(3):CD003336.
doi: 10.1002/14651858.CD003336.pub3.

Anticoagulation versus placebo for heart failure in sinus rhythm

Gregory Y H Lip  1 , Eduard Shantsila
Affiliations
Meta-Analysis

Anticoagulation versus placebo for heart failure in sinus rhythm

Gregory Y H Lip et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Patients with chronic heart failure (heart failure) are at risk of thromboembolic events, including stroke, pulmonary embolism and peripheral arterial embolism, whilst coronary ischaemic events also contribute to the progression of heart failure. Long-term oral anticoagulation is established in certain patient groups, including patients with heart failure and atrial fibrillation, but there is wide variation in the indications and use of oral anticoagulation in the broader heart failure population.

Objectives: To determine whether long-term oral anticoagulation reduces total deaths, cardiovascular deaths and major thromboembolic events in patients with heart failure.

Search methods: We updated the searches in June 2030 in the electronic databases CENTRAL (Issue 6, 2013) in The Cochrane Library, MEDLINE (OVID, 1946 to June week 1 2013) and EMBASE (OVID, 1980 to 2013 week 23). Reference lists of papers and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. Relevant authors were contacted to obtain further data. No language restrictions were applied.

Selection criteria: Randomised controlled trials (RCTs) comparing oral anticoagulants with placebo in adults with heart failure, and with treatment duration at least one month. Non-randomised studies were also included for assessing side effects. Inclusion decisions were made in duplicate and any disagreement between review authors was resolved by discussion or a third party.

Data collection and analysis: Two review authors independently assessed trials for inclusion and assessed the risks and benefits of antithrombotic therapy using relative measures of effects, such as odds ratio, accompanied by the 95% confidence intervals.

Main results: Two RCTs were identified. One compared warfarin, aspirin and no antithrombotic therapy and the second compared warfarin with placebo in patients with idiopathic dilated cardiomyopathy. Three small prospective controlled studies of warfarin in heart failure were also identified, but they were over 50 years old with methods not considered reliable by modern standards. In both WASH 2004 and HELAS 2006, there were no significant differences in the incidence of myocardial infarction, non-fatal stroke and death between patients taking oral anticoagulation and those taking placebo. Four retrospective non-randomised cohort analyses and four observational studies of oral anticoagulation in heart failure included differing populations of heart failure patients and reported contradictory results.

Authors' conclusions: Based on the two major randomised trials (HELAS 2006; WASH 2004), there is no convincing evidence that oral anticoagulant therapy modifies mortality or vascular events in patients with heart failure and sinus rhythm. Although oral anticoagulation is indicated in certain groups of patients with heart failure (for example those with atrial fibrillation), the available data does not support the routine use of anticoagulation in heart failure patients who remain in sinus rhythm.

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Conflict of interest statement

The study unit was a centre for the WATCH trial for which drugs and unrestricted grants were provided by Bristol Myers Squibb, Sanofi‐Synthelabo and Dupont pharmaceutical companies. It was also a centre for the WARCEF study, as well as other trials of antithrombotic therapy in CVD and stroke.

Clarification statement added from the Co‐ordinating Editor on 2 March 2020: This review was found by the Cochrane Funding Arbiters, post‐publication, to be noncompliant with the Cochrane conflict of interest policy, which includes the relevant parts of the Cochrane Commercial Sponsorship Policy. It will be updated within a year. The update will have a majority of authors and lead author free of conflicts.

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Quasi‐randomised studies of warfarin versus control in patients with chronic heart failure, Outcome 1 All cause deaths.
1.2
1.2. Analysis
Comparison 1 Quasi‐randomised studies of warfarin versus control in patients with chronic heart failure, Outcome 2 Cardiovascular deaths (stroke, myocardial infarction, pulmonary embolism, peripheral arterial embolism) and sudden deaths.
1.3
1.3. Analysis
Comparison 1 Quasi‐randomised studies of warfarin versus control in patients with chronic heart failure, Outcome 3 Non‐fatal cardiovascular events (non‐fatal stroke, myocardial infarction, pulmonary embolism, peripheral arterial embolism).
1.4
1.4. Analysis
Comparison 1 Quasi‐randomised studies of warfarin versus control in patients with chronic heart failure, Outcome 4 Major bleeding events.
2.1
2.1. Analysis
Comparison 2 Prospective studies of warfarin versus control in patients with chronic heart failure, Outcome 1 All cause deaths.
2.2
2.2. Analysis
Comparison 2 Prospective studies of warfarin versus control in patients with chronic heart failure, Outcome 2 Cardiovascular deaths (stroke, myocardial infarction, pulmonary embolism, peripheral arterial embolism) and sudden deaths.
2.3
2.3. Analysis
Comparison 2 Prospective studies of warfarin versus control in patients with chronic heart failure, Outcome 3 Non‐fatal cardiovascular events (non‐fatal stroke, myocardial infarction, pulmonary embolism, peripheral arterial embolism).
2.4
2.4. Analysis
Comparison 2 Prospective studies of warfarin versus control in patients with chronic heart failure, Outcome 4 Major bleeding events.
See this image and copyright information in PMC

Update of

Comment in

References

References to studies included in this review

Anderson 1950 {published data only}
    1. Anderson GM, Hull E. The effects of dicumarol upon the mortality and incidence of thromboembolic complications in congestive heart failure. American Heart Journal 1950;39:697‐702. - PubMed
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Harvey 1950 {published data only}
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References to studies excluded from this review

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SAVE 1997 {published data only}
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WATCH 2009 {published data only}
    1. Messie BM, Collins JF, Ammon SE, Armstrong PW, Cleland JG, Ezekowitz M, et al. Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial. Circulation Mar 31;119(12):1616‐24. - PubMed
Wishart 1948 {published data only}
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Additional references

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