A multicentre, double-blind, placebo-controlled trial of quinapril in mild, chronic heart failure

Angiotensin converting enzyme (ACE) inhibitors are of proven value in patients with severe chronic heart failure (CHF). Studies of the effects of ACE inhibitors on exercise capacity and quality of life in mild CHF have produced conflicting results. We have studied the effects of quinapril, a new ACE inhibitor with a relatively short plasma half-life, in mild CHF. Once daily (o.d.) dosing was compared with twice daily (b.i.d.) dosing in a three-way cross-over, double-blind, placebo-controlled trial. Thirty-two patients (two female), mean age 59 (range 32–76) years were enrolled in three cardiology centres in the U.K. Twenty-seven patients were in NYHA Class II, five in Class III. The aetiology of heart failure was coronary artery disease in 29 patients, and non-ischaemic in three. The mean (range) radionuclide ejection fraction was 20.4% (8%–47%). Following full familiarization with the protocol, the treadmill exercise time (modified Bruce protocol) was determined for each patient during a placebo run-in phase, and at the end of each of three 8-week double-blind treatment phases with quinapril o.d., quinapril b.i.d. (maximal total daily dose 20 mg) and placebo. Three patients were withdrawn due to adverse events while receiving quinapril (unstable angina, exacerbation of CHF and arrhythmia); there were no deaths and no patient was withdrawn due to hypotension. Mean exercise time (the primary end-point) was 65 s and53 s longer in patients receiving quinapril o.d. and b.i.d. respectively compared to placebo (both P <0.01, ANOVA). There was no significant period effect during the trial and no significant difference between the two quinapril dosing regimens. Quinapril had no significant effect on secondary end-points including ejection fraction functional class and quality of life. In conclusion, quinapril significantly improves the exercise capacity of patients with mild CHF. Once daily dosing is equally effective to twice daily dosing, indicating that a relatively short plasma half-life does not necessarily result in a short duration of effect during chronic dosing.