Long‐Term Therapy with Benazepril in Patients with Congestive Heart Failure: Effects on Clinical Status and Exercise Tolerance

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Abstract
Benazepril hydrochloride (CGS 14824A) is an orally active, nonsulfhydryl compound that is transformed in vivo to a long‐acting inhibitor of angiotensin‐converting enzyme (ACE). Previous studies have shown benazepril to lower blood pressure in hypertensive patients and to confer acute hemodynamic benefits in patients with congestive heart failure (CHF). In the current multicenter investigation, 16 patients with chronic CHF due to left ventricular systolic dysfunction (ejection fraction < 0.40 at rest) whose symptoms corresponded to New York Heart Association classes II to IV were given open‐label benazepril once daily in ascending doses of 2 to 20 mg and followed biweekly for 12 weeks. Evaluation of the 15 subjects who completed the trial showed a progressive increase in treadmill exercise duration (from 7.65 ± 3.64 [SD] minutes at baseline to 9.74 ± 3.66 minutes at 12 weeks, P < .001); augmentation of the mean left ventricular ejection fraction (from 0.266 ± 0.133 at baseline to 0.292 ± 0.136 at 12 weeks, P < .025); relief of exertional dyspnea in 7 of the 15 patients (P < .02); and improvement in global symptomatic status in 10 of the patients (P < .01). These responses were accompanied by a reduction in serum ACE activity of 75% (from 27.2 ± 10.5 IU/L at baseline to 6.7 ± 1.9 IU/L at 12 weeks, P < .001), which was independent of dose and duration of treatment. The magnitude of ACE inhibition did not correlate with changes in the efficacy variables. Aside from two instances of symptomatic hypotension (one of which was complicated by volume depletion), the drug was well tolerated. Long‐term therapy with benazepril for patients with CHF shows promise. A large‐scale, double‐blind trial of benazepril in this population is currently in progress.