WARCEF

Warfarin versus Aspirin Reduced Cardiac Ejection Fraction study (2012)

Condition

Prevention of vascular events in patients with heart failure and sinus rhythm

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Objective

To compare the efficacy of warfarin and ASA in preventing death, ischemic stroke, and intracerebral hemorrhage in patients with heart failure (LVEF ≤35%) and sinus rhythm

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Trial design

Randomized, double-blind, phase III trial
Active treatment: warfarin (INR 2.5–3.0) plus placebo (n=1142)
Control treatment: ASA 325 mg once daily plus placebo (n=1163)

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Endpoints

Primary efficacy endpoint: time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause
Primary safety endpoint: composite of death, ischemic stroke, intracerebral hemorrhage, or intracranial hemorrhage
Secondary outcomes: death, ischemic stroke, intracerebral hemorrhage, myocardial infarction, or hospitalization for heart failure

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Trial participants

2305 patients >18 years with a left ventricular ejection fraction (LVEF) ≤35% or a wall motion index ≤1.2, who do not have atrial fibrillation or mechanical cardiac valves. Patients must be treated with a betablocker, an ACE inhibitor (or angiotensin-receptor blocker), or hydralazine and nitrates

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Results

Efficacy outcome: As compared with ASA, warfarin did not significantly reduce the rate of the primary outcome (7.47 events per 100 patient-years in the warfarin group and 7.93 in the ASA group). Throughout the follow-up period, warfarin was associated with a significant reduction in the rate of ischemic stroke (0.72 vs. 1.36 events per 100 patient-years). With respect to the main secondary outcome (first event in the composite of death, ischemic stroke, intracerebral hemorrhage, myocardial infarction, or hospitalization for heart failure), there was no significant difference between the warfarin and ASA groups (12.70 vs. 12.15 events per 100 patient-years)
Safety outcome: The overall safety outcome did not differ significantly between the two treatment groups. But the rate of major hemorrhage was significantly higher with warfarin than with ASA (1.78 vs. 0.87 events per 100 patient-years)

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Summary

Efficacy: There was no significant overall difference between warfarin and ASA with respect to the primary outcome of death, ischemic stroke, or intracerebral hemorrhage. However, warfarin was associated with a significant reduction in the risk of ischemic stroke
Safety: The benefit of warfarin in reducing the risk of ischemic stroke was offset by a significant increase in the rate of major bleeding

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Reference

Homma S, Thompson JL, Pullicino PM, Levin B, Freudenberger RS, Teerlink JR, Ammon SE, Graham S, Sacco RL, Mann DL, Mohr JP, Massie BM, Labovitz AJ, Anker SD, Lok DJ, Ponikowski P, Estol CJ, Lip GY, Di Tullio MR, Sanford AR, Mejia V, Gabriel AP, del Valle ML, Buchsbaum R fot the WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med 2012;366:1859-1869

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Corresponding author

Shunichi Homma, MD, Columbia University Medical Center, PH 3-342, 622 West 168th St., New York, NY 10032, sh23@columbia.edu

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