Clinical Evaluation of Enalapril Maleate for Treatment of Heart Failure in Dogs

Tadashi NAGATA; Naoyuki TAKEMURA; Makoto WASHIZU; Shigekatsu MOTOYOSHI; Yoshito WAKAO; Mitsugi TAKAHASHI; Hideki MATSUMOTO; Yoshihisa YAMANE; Raffaele A. RONCALLI

doi:10.11276/jsvc1984.29.14

Tadashi NAGATA, Naoyuki TAKEMURA, Makoto WASHIZU, Shigekatsu MOTOYOSHI, Yoshito WAKAO, Mitsugi TAKAHASHI, Hideki MATSUMOTO, Yoshihisa YAMANE, Raffaele A. RONCALLI

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Keywords: ACE inhibitor, chronic heart failure, dogs, enalapril, vasodilator

JOURNAL FREE ACCESS

1996 Volume 29 Issue 1 Pages 14-26

DOI https://doi.org/10.11276/jsvc1984.29.14

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Published: 1996 Received: - Available on J-STAGE: September 17, 2009 Accepted: March 21, 1996 Advance online publication: - Revised: -
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Date of correction: September 17, 2009 Reason for correction: - Correction: CITATION Details: Wrong : 1) Keene, B. W. and J. E. Rush : Therapy of heart failure. In : Textbook of Veterinary Internal Medicine (3rd ed.), Ettinger, S. J. ed., pp. 939-975, W. B. Saunders Company, Pennsylvania, 1989.
2) Ettinger, S., Lusk, R., Brayley, K. and J. Lunney (1992) : Evaluation of enalapril therapy in dogs with heart failure in a large multicenter study cooperative veterinary enalapril (cove) study group. Proc. 10th ACVIM Forum : 584-585.
3) Leddy, C. L., Wilen, M. and J. A. Franciosa (1983) : Effects of a new angiotensin converting enzyme inhibitor, enalapril, in acute and chronic left ventricular failure in dogs. J. Clin PharmacoL, 23, 189-198.
4) Hamlin, R. L., Benitz, A. M. and K. Samura (1990) : Iatrogenic mitral regurgitation-A model of left-sided congestive heart failure. Proc. 8th ACVIM Forum : 851-853.
5) Knight, D. H. : Pathophysiology of heart failure (3rd ed.), Ettinger, S. J. ed., pp. 899-922, W. B. Saunders Company, Pennsylvania, 1989.
6) Ettinger, S. J., Benitz, A. M. and G. F. Ericsson (1994) : Relationships of enalapril with other CHF treatment modalities. Proc. 12th ACVIM Forum : 251-253.
7) Fox, P. R. (1992) : The effect of drug therapy on clinical characteristics and outcome in dogs with heart failure. Proc. 10th ACVIM Forum : 592-593.
8) Sisson, D. D. (1992) : Hemodynamic, echocardiographic, radiographic, and clinical effects of enalapril in dogs with chronic heart failure. Proc. 10th ACVIM Forum : 589-591.
9) Arnold, S., Williams, R. L., Ports, T. A., Baughman, R. A., Benet, L. Z., Parmley, W. W. and K. Chatterjee (1979) : Attenuation of prazosin effect on cardiac output in chronic heart failure. Ann. Intern. Med., 91, 345-349.
10) Packer, M., Meller, J., Gorlin, R. and M. V. Herman (1979) : Hemodynamic and clinical tachy phylaxis to prazosin-medicated afterload reduction in severe chronic congestive heart failure. Circulation, 59, 531-539.
11) Papademetriou, V. (1986) : Diuretics, hypokalemia, and cardiac arrhythmias : a critical analysis. Am. Heart J., 111, 1217-1224.

Right : 1) Keene, B. W. and J. E. Rush : Therapy of heart failure. In : Textbook of Veterinary Internal Medicine (3rd ed.), Ettinger, S. J. ed., pp. 939-975, W. B. Saunders Company, Pennsylvania, 1989.
2) Ettinger, S., Lusk, R., Brayley, K. and J. Lunney (1992) : Evaluation of enalapril therapy in dogs with heart failure in a large multicenter study cooperative veterinary enalapril (cove) study group. Proc. 10th ACVIM Forum : 584-585.
3) Leddy, C. L., Wilen, M. and J. A. Franciosa (1983) : Effects of a new angiotensin converting enzyme inhibitor, enalapril, in acute and chronic left ventricular failure in dogs. J. Clin Pharmacol, 23, 189-198.
4) Hamlin, R. L., Benitz, A. M. and K. Samura (1990) : Iatrogenic mitral regurgitation-A model of left-sided congestive heart failure. Proc. 8th ACVIM Forum : 851-853.
5) Knight, D. H. : Pathophysiology of heart failure (3rd ed.), Ettinger, S. J. ed., pp. 899-922, W. B. Saunders Company, Pennsylvania, 1989.
6) Ettinger, S. J., Benitz, A. M. and G. F. Ericsson (1994) : Relationships of enalapril with other CHF treatment modalities. Proc. 12th ACVIM Forum : 251-253.
7) Fox, P. R. (1992) : The effect of drug therapy on clinical characteristics and outcome in dogs with heart failure. Proc. 10th ACVIM Forum : 592-593.
8) Sisson, D. D. (1992) : Hemodynamic, echocardiographic, radiographic, and clinical effects of enalapril in dogs with chronic heart failure. Proc. 10th ACVIM Forum : 589-591.
9) Arnold, S., Williams, R. L., Ports, T. A., Baughman, R. A., Benet, L. Z., Parmley, W. W. and K. Chatterjee (1979) : Attenuation of prazosin effect on cardiac output in chronic heart failure. Ann. Intern. Med., 91, 345-349.
10) Packer, M., Meller, J., Gorlin, R. and M. V. Herman (1979) : Hemodynamic and clinical tachyphylaxis to prazosin-medicated afterload reduction in severe chronic congestive heart failure. Circulation, 59, 531-539.
11) Papademetriou, V. (1986) : Diuretics, hypokalemia, and cardiac arrhythmias : a critical analysis. Am. Heart J., 111, 1217-1224.

Abstract

A multi-center field study to assess the safety and efficacy of enalapril maleate (enalapril) in household dogs with naturally acquired Class III or Class IV heart failure caused mainly by mitral regurgitation was conducted at 20 animal hospitals in Japan. One hundred and thirty-six dogs of various breeds and each sex, aged 5 to 18 years and weighing 1.4 to 19.7 kg were included in the study and were randomly allocated to a vehicle control group (control group) or to an enalapril treatment group (enalapril group). Dogs in the enalapril group received the medication at the starting dose of approximately 0.25 mg/kg once a day (s.i.d.) for 7 days, followed by 0.5 mg/kg s.i.d., with an option to increase the dose on Day 14 to 0.5 mg/kg twice a day (b.i.d.) based on the results of physical examination and laboratory testing on Day 14. Dogs in the control group received vehicle tablets. Doses were administered for approximately 28 days. All but one dogs received standard therapy for congestive heart failure : 125 (92%) dogs received furosemide (maximum 4 mg/kg/day) and 125 (92%) dogs received digoxin (maximum 10μg/kg/day) at the discretion of the investigator. Sixtyseven and 69 dogs were allocated to the control group and the enalapril group, respectively. Forty-four (66%) dogs in the control group completed the study when compared to 57 (83%) dogs in the enalapril group. The improvement from baseline to Day 28 was significantly greater for dogs in the enalapril group than for those in the control group for all scored parameters: activity, mobility, appetite, coughing, respiratory effort, pulmonary edema, and class of heart failure. Overall evaluation judged by the investigators were significantly better for the enalapril-treated dogs than for the control dogs on Days 7, 14 and 28. No differences were observed between the enalapril group and the control group for changes in all laboratory testing parameters (serum chemistry, electrolytes, etc.). No adverse reactions attributable to enalapril treatment were observed. The results of the study demonstrate that enalapril administered at 0.25 to 0.5 mg/kg s.i.d. with standard therapy of heart failure improves the clinical signs associated with heart failure. There were no enalapril-related adverse reactions.

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