Efficacy and acceptability of perindopril in mild to moderate chronic congestive heart failure

The aim of this 3-month double-blind, placebo-controlled, multicenter trial was to evaluate the clinical efficacy and safety of perindopril, a new long-acting angiotensin-converting enzyme inhibitor in the second-line treatment of mild to moderate chronic congestive heart failure. After a run-in period of at least 14 days, 125 patients with grade II or III New York Heart Association chronic congestive heart failure on baseline diuretic therapy were randomized to perindopril, 2 mg (n = 61), or placebo (n = 64), once daily. Assessment was at 2-week intervals for the first month and then monthly for the 2 following months. After 2 weeks, active treatment was increased to perindopril, 4 mg once daily, if systolic blood pressure was 100 mm Hg or greater. Apart from sex, the two groups were homogeneous before treatment. As shown by the end-point analysis, the increase in exercise time was greater with perindopril than with placebo for both the ergometric bicycle (+111 ± 21 versus +16 ± 20 seconds; p = 0.002) and the treadmill (+171 ± 39 versus +36 ± 42 seconds; p = 0.024). Compared with placebo, this increase in exercise tolerance with perindopril was accompanied by an improvement in New York Heart Association functional class (p = 0.009), overall heart failure severity score (p < 0.001), and cardiothoracic ratio (p = 0.05). Of the 12 withdrawals from the study, seven were attributed to adverse events, two in the perindopril group and five, including one death, in the placebo group. Changes in blood pressure were not significantly different between the two groups except for a moderate fall in erect diastolic blood pressure with perindopril (−4 ± 2 mm Hg vs +2 ± 1 mm Hg; p = 0.007). Plasma creatinine levels remained stable in each group. In conclusion, in patients with mild to moderate chronic congestive heart failure on baseline diuretic therapy, perindopril increases functional capacity and exercise tolerance with a good safety profile, particularly in terms of blood pressure and renal function.