Background: The American Heart Association estimates that the prevalence of heart failure (HF) in the U.S. is currently 5.7 million people. While the use of ACE inhibitors and beta-blockers are well established therapy to reduce morbidity and mortality, the use of anticoagulation and antiplatelet therapies remain controversial in the HF population.
Heart failure increases the risk of thrombotic events through several mechanisms. The primary etiology of thromboembolic events in HF is atrial fibrillation—heart failure is an independent risk factor for atrial fibrillation; that risk increases with increasing disease severity.1-3 Heart failure is a relatively hypercoagulability state because of coronary blood stasis as well as increases in procoagulant factors.4,5
While it is clear based on CHADS2 risk assessment that many HF patients with concomitant atrial fibrillation benefit from anticoagulation therapy6,7 (in a patient with a CHADS2 score of 1 [assuming HF only] adjusted stroke risk is 2.8 per 100 person years); it is less clear if anticoagulation therapy is beneficial for those who remain in normal sinus rhythm.
The American College of Chest Physicians guidelines8 as well as the 2009 update to the joint American College of Cardiology/American Heart Association heart failure guidelines9 are in agreement that there is no clear indication for anticoagulation in the absence of atrial fibrillation or other condition (e.g. previous VTE, genetic predisposition, recent MI) that would otherwise place the patient at high risk of a thromboembolic event. For heart failure and atrial fibrillation or after an acute myocardial infarction, the guidelines are consistent with those for similar patients without heart failure; target INR range of 2-3.
Retrospective analyses have supported the use of anticoagulants in heart failure. Relative risk reductions in stroke of up to 81%10,11 as well as reductions in all-causes mortality were reported in randomized trials. The seeming strength of these data is tempered by fact that all the analyses were retrospective in nature, and the trials were not designed to specifically evaluate anticoagulation therapy. Many of the subjects in these trials had concomitant atrial fibrillation at either baseline or follow-up.
Another unanswered controversy is the use of ASA in heart failure. Aspirin has been hypothesized to interact with ACE inhibitors and moderate prostaglandins production12 and the evidence for its use in patients with heart failure is equivocal.
The WATCH trial13 (randomized trial of warfarin, aspirin and clopidogrel in patients with chronic heart failure) was undertaken to determine if there is a difference in the primary composite outcome of all-cause mortality, nonfatal MI and nonfatal stroke in heart failure patients in normal sinus rhythm and reduced LVEF. 142 sites in the North America and the U.K. randomized patients 1:1:1 to warfarin (target INR 2.5–3.0), aspirin (162mg daily) or clopidogrel (75mg daily). Planned enrollment of 1500 subjects per treatment arm was not met; the trial was terminated early due to the slow enrollment. As a result of low numbers, the trial was only ...