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Results of the veterinary enalapril trial to prove reduction in onset of heart failure in dogs chronically treated with enalapril alone for compensated, naturally occurring mitral valve insufficiency
Authors:Atkins Clarke E  Keene Bruce W  Brown William A  Coats Julie R  Crawford Mary Ann  DeFrancesco Teresa C  Edwards N Joel  Fox Phillip R  Lehmkuhl Linda B  Luethy Michael W  Meurs Kathryn M  Petrie Jean-Paul  Pipers Frank S  Rosenthal Steven L  Sidley Jennifer A  Straus Justin H
Affiliation:Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Abstract:OBJECTIVE: To determine the efficacy of long-term enalapril administration in delaying the onset of congestive heart failure (CHF). DESIGN: Placebo-controlled, double-blind, multicenter, randomized trial. ANIMALS: 124 dogs with compensated mitral valve regurgitation (MR). PROCEDURES: Dogs randomly assigned to receive enalapril or placebo were monitored for the primary endpoint of onset of CHF for < or = 58 months. Secondary endpoints included time from study entry to the combined endpoint of CHF-all-cause death; number of dogs free of CHF at 500, 1,000, and 1,500 days; and mean number of CHF-free days. RESULTS: Kaplan-Meier estimates of the effect of enalapril on the primary endpoint did not reveal a significant treatment benefit. Chronic enalapril administration did have a significant benefit on the combined endpoint of CHF-all-cause death (benefit was 317 days [10.6 months]). Dogs receiving enalapril remained free of CHF for a significantly longer time than those receiving placebo and were significantly more likely to be free of CHF at day 500 and at study end. CONCLUSIONS AND CLINICAL RELEVANCE: Chronic enalapril treatment of dogs with naturally occurring, moderate to severe MR significantly delayed onset of CHF, compared with placebo, on the basis of number of CHF-free days, number of dogs free of CHF at days 500 and study end, and increased time to a combined secondary endpoint of CHF-all-cause death. Improvement in the primary endpoint, CHF-free survival, was not significant. Results suggest that enalapril modestly delays the onset of CHF in dogs with moderate to severe MR.
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