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Evaluation of benazepril in cats with heart disease in a prospective, randomized, blinded, placebo-controlled clinical trial

King JN, Martin M, Chetboul V, Ferasin L, French AT, Strehlau G, et al. Evaluation of benazepril in cats with heart disease in a prospective, randomized, blinded, placebo-controlled clinical trial. J Vet Intern Med [Internet]. 2019 Sep 27 [cited 2019 Oct 4];jvim.15572

Heart disease is a common cause of illness and death in cats. A wide range of medications are used to manage and treat heart disease, however few therapies have bene consistentlky shown to delay the onset of congestive heart failure or to manage it effectively once it occurs. Angiotensin Converting Enzyme Inhibitors (ACEIs) have been widely used in humane, canine, and feline medicine as an aide in the treatment of cardiac disease. Benazepril is a commonly used ACEI in veterinary medicine; and there has been data to suggest that its use results in improved parameters in cats with HCM. However, there has been a lack of controlled, prospective studies on ACEIs in cats.

The purpose of this manuscript was to determine if the use of benazepril delayed the time to treatment failure in cats with cardiac disease. The study was designed as a placebo controlled, double blinded, prospective multi center clinical trial.

Recruited cats were client owned animals with heart disease requiring treatment, including both animals with CHF and those without CHF but deemed by the investigator to require therapy. Cats could be enrolled with any form of cardiomyopathy, valvular disease, or congenital disease not correctable by surgery. Ultimately all animals were considered as a group and not stratified. Cats were excluded for surgically correctable disease, diabetes, hyperthyroidism, endocarditis, pericardial disease, heartworm, pregnancy/lactation, or systemic emboli. Cats with DCM were required to receive taurine; other allowed cardiac medications included furosemide, digoxin, and aspirin.

Animals were randomized to receive either 0.5-1.0mg/kg benazepril once daily, or placebo.

The primary endpoint was treatment failure. Criteria for heart disease related treatment failure included death or euthanasia due to worsening cardiac condition, persistent unacceptably high heart rate, repeated thoracentesis, or ventricular arrhythmia requiring treatment. All cause treatment failure included cardiac failure as well as development of hyperthyroidism, death or euthanasia for non cardiac reasons, or serious adverse events.

Secondary endpoints included owner assessed quality of life, left atrial diameter, and left ventricular wall thickness. Investigators also assessed a range of factors related to heart disease (ie peripheral and pulmonary edema, dyspnea, etc).

151 cats were enrolled from 23 centers. 77 received benazepril and 74 received placebo. 38% of the cats in the treatment group reached the cardiac endpoint, while 30% of placebo cats reached this endpoint. This was not a statistically significant difference, nor was there a difference in non cardiac treatment failure.

There was also no significant difference detected between groups in time to event, quality of life markers, clinical signs of heart disease, or echocardiographic parameters.

Adverse effects were uncommon and not different between treatment and placebo. No adverse effects on chemical or hematologic parameters was seen.

The authors of the study conclude that there was no effect of benazepril therapy  on primary or secondary outcomes of cardiac disease in cats.

Some weaknesses were present in this study. While the methodology and study design as a prospective, controlled trial provides a high level of support for the conclusions, and the study was adequately powered, there was a lack of subgroup analysis and it is possible the different effects may be seen in some groups of cats compared to others (ie HCM vs DCM). There was also a lack of differentiation of causes of treatment failure. Some of the concurrent medications are also no longer as relevant in the modern day as when the study began (ie aspirin has largely been supplanted by clopridogrel).

Of particular positive note, this study appears to have been sponsored, at least in part, by a manufacturer of benazepril; it nice to see the willingness of industry to publish negative data on their own products.

Overall, this study indicates that benazepril is not likely useful in the management of clinical or pre-clinical heart disease in cats. Based on this, prescribing this drug to cats with heart disease is likely no longer indicated.

See Also

Rishniw M, Pion PD. Is treatment of feline hypertrophic cardiomyopathy based in science or faith? A survey of cardiologists and a literature search. J Feline Med Surg. 2011;13:487-497.

Côté E. Feline congestive heart failure current diagnosis and management. Vet Clin Small Anim. 2017;47:1055-1064.

Ettinger SJ, Benitz AM, Ericsson GF, et al. Effects of enalapril maleate on survival of dogs with naturally acquired heart failure. The Long- Term Investigation of Veterinary Enalapril (LIVE) Study Group. J Am Vet Med Assoc. 1998;213:1573-1577.