Randomized Trial of Warfarin, Aspirin, and Clopidogrel in Patients With Chronic Heart Failure

Abstract

Background-Chronic heart failure remains a major cause of mortality and morbidity. The role of antithrombotic therapy in patients with chronic heart failure has long been debated. The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm. Methods and Results-This prospective, randomized clinical trial of open-label warfarin (target international normalized ratio of 2.5 to 3.0) and double-blind treatment with either aspirin (162 mg once daily) or clopidogrel (75 mg once daily) had a 30-month enrollment period and a minimum of 12 months of treatment. We enrolled 1587 men and women Ն18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of Յ35%. The primary outcome was the time to first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke. For the primary composite end point, the hazard ratios were as follows: for warfarin versus aspirin, 0.

Dual Antiplatelet Compared to Triple Antithrombotic Therapy in Anterior Wall Acute Myocardial Infarction Complicated by Depressed Left Ventricular Ejection Fraction

“…Th e low overall rates of clinical embolism and LVT found are consistent with other studies that have evaluated the clinical course after an acute anterior wall MI in the PCI era (3,5,11,13,15). Interestingly, our results also mirror similar results seen in chronic heart failure patients with signifi cant systolic dysfunction (16,17). For example, in the WARCEF study of patients with heart failure in sinus rhythm, approximately 40% of whom had an ischemic cardiomyopathy and were randomized to either anticoagulation with warfarin or single antiplatelet therapy with aspirin, no diff erence was found in the rates of death, stroke, or intracerebral hemorrhage between the groups (16).…”

Coexisting Cardiac and Hematologic Disorders

“…The addition of anticoagulant and/or antithrombotic therapy in those with coexisting atrial fibrillation or previous thromboembolic event is recommended; however, anticoagulant therapy for patients in sinus rhythm with reduced ejection fraction is less clear. Multiple randomized controlled trials have compared the use of warfarin, aspirin, and clopidigrel in this patient population with conflicting results [46][47][48] . Aspirin has been associated with increased risk for hospitalization and gastrointestinal bleeding; however, this may be due to an as yet undefined interaction with ACE inhibitors 49 .…”

Antithrombotic therapy in heart failure

“…The American WATCH trial evaluated the optimal antithrombotic strategy for thromboembolism prevention in patients with heart failure in sinus rhythm and the clinical interactions between aspirin and ACE inhibitors [4]. The trial was planned to include 4500 patients, but randomisation was prematurely discontinued due to slow recruitment.…”

“…Previous observations have addressed this and found a decreased long-term mortality benefit of ACE inhibitors for in 6 placebo-controlled trials in patients with or without aspirin [2] (Table 1). However, until the WATCH and WASH trials [3][4][5] there had not been a randomised study investigating aspirin in heart failure patients on ACE inhibitors.…”