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Angiotensin-Converting Enzyme Inhibitors


Angiotensin-converting enzyme (ACE) inhibitors are widely used in treating chronic CHF in dogs. In the pathogenesis of CHF, the proteolytic enzyme renin is released by the kidneys and acts on angiotensinogen, which is produced by the liver and distributed in the blood, to produce angiotensin I. The formation of angiotensin II from angiotensin I occurs through the action of ACE. Angiotensin II causes retention of Na+ and water, in part through stimulation of the synthesis and release of aldosterone by the adrenal cortex. Angiotensin II also causes vasoconstriction, thus increasing vascular resistance. By inhibiting the formation of angiotensin II, ACE inhibitors prevent vasoconstriction and reduce the retention of Na+ and water in animals with CHF. ACE inhibitors are balanced vasodilators, reducing both preload and afterload. The effects during CHF include decreased vascular resistance and cardiac filling pressures and increased cardiac output and exercise tolerance.

Enalapril maleate is a widely used ACE inhibitor and is available in various sized tablets for oral administration. It can delay mortality while improving quality of life in dogs with CHF. Captopril was the first ACE inhibitor developed for people and had been used extra-label in dogs and cats. Compared with enalapril, captopril has a greater propensity for GI side effects and a shorter half-life in dogs, necessitating more frequent dosing. Benazepril is approved in several countries outside the USA for treating CHF in dogs.

After absorption from the GI tract, enalapril is converted in the liver to the active metabolite enalaprilat. Therefore, enalapril has a delayed onset of action (4–6 hr) but a duration of action of 12–14 hr. The half-life of enalapril (enalaprilat) is increased in animals with severe CHF or renal failure.

Hypotension may develop with concurrent use of ACE inhibitors and other vasodilators or diuretics. Concurrent use of potassium-sparing diuretics (ie, spironolactone) may cause hyperkalemia. Based on clinical trial data, enalapril appears safe when used concomitantly with furosemide, digoxin, antiarrhythmics, β-blockers, bronchodilators, and cough suppressants.

Relative to other drugs used to treat CHF, ACE inhibitors may have a better safety profile. However, azotemia may develop, and monitoring of BUN and creatinine (with possible dosage adjustments) is warranted. Other possible adverse effects include GI disturbances (anorexia, vomiting, diarrhea), hypotension, syncope, weakness, ataxia, and renal dysfunction.

ACE inhibitors are indicated in the treatment of CHF in dogs and cats stemming from valvular heart disease and dilated cardiomyopathy. While ACE inhibitors may delay the onset of CHF in asymptomatic animals with cardiac disease, this has yet to be proved. ACE inhibitors may also be considered for management of hypertension in cats. The approved use of enalapril in dogs is as adjunctive therapy with furosemide and digoxin for dilated cardiomyopathy, or with furosemide with or without digoxin for chronic valvular insufficiency. The dosage of enalapril for treating CHF in dogs is 0.5 mg/kg, PO, sid. If, after 14 days, the clinical response is inadequate, enalapril may be administered at 0.5 mg/kg, PO, bid. Alternatively, therapy with enalapril alone at 0.5 mg/kg, sid, may be initiated in asymptomatic animals or in animals with mild signs related to heart failure. In animals with moderate to advanced signs, enalapril can be administered at 0.5 mg/kg, bid, with or without furosemide or digoxin (or both).

Like enalapril, benazepril is a prodrug that undergoes metabolism by the liver to the active benazeprilat. Benazepril is indicated for treatment of CHF in dogs. Benazeprilat inhibits plasma ACE for >24 hr after a single dose. About half of benazeprilat undergoes hepatic excretion, a possible advantage in animals with renal failure. The dosage of benazepril is 0.25–0.5 mg/kg, PO, sid in dogs and 0.5–1 mg/kg, PO, sid in cats.

Lisinopril is another ACE-inhibitor occasionally used to treat CHF in dogs; however, efficacy and safety in dogs and cats have yet to be established. Unlike enalapril, lisinopril does not require hepatic activation. A suggested dosage for dogs is 0.5 mg/kg, PO, sid.

Last full review/revision March 2012 by Mark J. Novotny, DVM, MS, PhD, DACVCP

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