Lip, Gregory YH, Wrigley, Benjamin J, Pisters, Ron

Morbidity and mortality in patients with symptomatic chronic heart failure is high and it predisposes them to stroke and thromboembolism, which in turn contribute to high mortality from heart failure. To determine the effect of antiplatelet agents when compared to placebo or anticoagulant therapy on death and/or major thromboembolic events in adults with heart failure who are in sinus rhythm. We updated the searches in February 2010 on CENTRAL and DARE on The Cochrane Library (Issue 1, 2010), MEDLINE (1966 to February 2010) and EMBASE (1998 to February 2010). Reference lists of papers and abstracts from cardiology meetings were searched. Authors of studies were contacted for further information. No language restrictions were applied. Randomised parallel group placebo or controlled trials comparing antiplatelet therapy with control or anticoagulation in adults with chronic heart failure in sinus rhythm. Treatment for at least one month. To assess any adverse effects, cohort study and non-randomised controlled studies were assessed. Orally administered antiplatelet agents for example non-steroidal anti-inflammatory agents, ticlopidine, clopidogrel, dipyridamole, aspirin compared with anticoagulant agents for example: coumarins, warfarin or placebo. Four 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 with 95% confidence intervals. The data extracted included data relating to the complexities of the topic area, such as patient characteristics and concomitant treatments, as well as data relating to study eligibility, quality, and outcomes. Non-randomised studies were used to identify side-effects caused by anticoagulants. Three randomised controlled trials (RCTs) were included. One compared warfarin versus aspirin versus no antithrombotic therapy (WASH 2004) and showed no significant difference in death, MI or stroke across the groups. Another compared aspirin and warfarin in patients with underlying ischaemic heart disease (HELAS 2006) and this showed no significant difference in death, MI or stroke between the groups. One large RCT (WATCH 2009) compared warfarin and antiplatelet therapy (aspirin, clopidogrel). The rates of death, MI and stroke were similar across each treatment group. In pooled analyses there was no evidence of difference between Warfarin and Aspirin in all cause deaths (three studies 1396 participants, OR 0.85 95% CI 0.64, 1.11), or cardiovascular deaths (three studies 1396 participants OR 0.97 95% CI 0.67, 1.12). There was evidence that Warfarin was associated with greater odds of major bleeding events (three studies, 1396 participants OR 1.82 95% CI 1.08, 3.07). Three retrospective, non-randomised cohort studies from the V-HeFT, SOLVD and SAVE trials examining the role of ACE inhibitors have examined the role of aspirin therapy +/- anticoagulant therapy in patients with heart failure and/or left ventricular systolic dysfunction and were reviewed for adverse events. The results from these trials were conflicting. At present there is little evidence from long term RCTs to recommend the use of antiplatelet therapy to prevent thromboembolism in patients with heart failure in sinus rhythm. A possible interaction with ACE inhibitors may reduce the efficacy of aspirin, although this evidence is mainly from retrospective analyses of trial cohorts and two RCTs. There is also no current evidence to support the use of oral anticoagulation (when compared to aspirin/clopidogrel) in patients with heart failure in sinus rhythm. Anticoagulation/antiplatelet therapy should be reserved for heart failure patients with other comorbidities (such as atrial fibrillation or underlying coronary artery disease) who may still benefit from these therapies.