Anticoagulation versus placebo for heart failure in sinus rhythm

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 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 and/or major thromboembolic events in patients with heart failure.

Search methods: We updated the searches in February 2010 on CENTRAL on The Cochrane Library (Issue 1, 2010), MEDLINE (2000 to February 2010) and EMBASE (1998 to February 2010). 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lists of papers and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies.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 duplicated, disagreement resolved by discussion or a third party.

Data collection and analysis: Four review authors independently assessed trials for inclusion and assessed the risks and benefits from antithrombotic therapy using relative measures of effects, such as odds ratio, accompanied with 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 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 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 atrial fibrillation), the data available does not support its routine use in heart failure patients who remain in sinus rhythm. A large randomised trial of warfarin in heart failure patients in sinus rhythm is currently in progress and data from this trial will be a useful addition to this topic.