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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

Clarke E. Atkins DVM, DACVIM1, Bruce W. Keene DVM, MS, DACVIM2, William A. Brown DVM, DACVIM3, Julie R. Coats4, Mary Ann Crawford DVM, DACVIM5, Teresa C. DeFrancesco DVM, DACVIM6, N. Joel Edwards DVM, DACVIM7, Phillip R. Fox DVM, DACVIM8, Linda B. Lehmkuhl DVM, DACVIM9, Michael W. Luethy DVM, DACVIM10, Kathryn M. Meurs DVM, PhD, DACVIM11, Jean-Paul Petrie DVM, DACVIM12, Frank S. Pipers DVM, PhD13, Steven L. Rosenthal DVM, DACVIM14, Jennifer A. Sidley DVM, DACVIM15, and Justin H. Straus DVM, DACVIM16
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  • 1 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606
  • | 2 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606
  • | 3 Veterinary Cardiology Consults, 1886 Birmingham Blvd, Birmingham, MI 48009
  • | 4 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606
  • | 5 Oradell Animal Hospital, 481 Kinderkamack Rd, Oradell, NJ 07649
  • | 6 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606
  • | 7 Capital Region Veterinary Medical Specialties, 1506 Western Ave, Albany, NY 12203
  • | 8 The Animal Medical Center, 510 E 62nd St, New York, NY 10021
  • | 9 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210
  • | 10 Cardioscope Pet Referral Service, 1820 Frontage Rd, Northbrook, IL 60062
  • | 11 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210
  • | 12 The Animal Medical Center, 510 E 62nd St, New York, NY 10021
  • | 13 Merial Ltd, 3239 Satellite Blvd, Duluth, GA 30096
  • | 14 Chesapeake Veterinary Referral Center, 808 Bestgate Rd, Annapolis, MD 21401
  • | 15 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606
  • | 16 Oradell Animal Hospital, 481 Kinderkamack Rd, Oradell, NJ 07649

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 ≤ 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.

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 ≤ 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.

Contributor Notes

Ms. Coats' present address is 2601 Bethlehem Church Rd, Gold Hill, NC 28071. Dr. Edwards' present address is Upstate Veterinary Specialties, 222 Troy-Schenectady Rd, Latham, NY 12110. Dr. Lehmkuhl's present address is MedVet Specialty Clinic, 5747 Cleveland Ave, Columbus, OH 43231. Dr. Meurs' present address is Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164. Dr. Pipers' present address is 350 Polk Dr, Sarasota, FL 34236. Dr. Sidley's present address is Chesapeake Veterinary Referral Center, 808 Bestgate Rd, Annapolis, MD 21401. Dr. Straus' present address is Animal Emergency and Referral Center, 647 Bloomfield Ave, West Caldwell, NJ 07006.

Supported by a grant from Merial Ltd.

Presented in part at the 20th Annual American College of Veterinary Internal Medicine Forum, Dallas, May 2002.

The authors thank Laura Gardner and Dr. Marty Stebbins for assistance with statistics and Anne Myers, Petra Guity, and Allison Klein for technical assistance.

Address correspondence to Dr. Atkins.