A Comparative Study of the First Dose Hypotensive Effects of Captopril and Perindopril in Patients with Heart Failure

Abstract

Angiotensin converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with heart failure and are a first-line therapy for chronic heart failure. However, the first-dose may be associated with asymptomatic or symptomatic hypotension. In previous small series with different ACE inhibitors, different blood pressure responses have been reported. We defined hypotension as a fall in mean blood pressure ≥20 mm Hg and an absolute value of systolic blood pressure ≤90 mm Hg and diastolic blood pressure ≤60 mm Hg. We studied the evolution of mean, systolic and diastolic blood pressure after initiation of perindopril and captopril treatments in a multicentre, double-blind, randomised, comparative, prospective study. One hundred seventy-six patients, mean age 64.9 ± 12.1 years, 116 men, with symptomatic heart failure, NYHA class II–IV, and a left ventricular ejection fraction <40%, were randomised to receive a single dose of captopril 6.25 mg (n = 85) or perindopril 2 mg, (n = 91). Systolic and diastolic blood pressure were recorded with Dinamap every 15 minutes during a baseline period of 2 hours, every 30 minutes from 2 to 7 hours and at 8 hours after the drug administration. Baseline characteristics of both groups were similar (demography, heart failure aetiology, NYHA class and blood pressure). Throughout the study there were 23 asymptomatic episodes of hypotension in the captopril group and 6 in the perindopril group (p = 0.039). One patient in the captopril group had symptomatic episodes.

Mean blood pressure falls were significantly higher in the captopril versus perindopril group at 60 minutes (−4.6 mm Hg vs +0.7 mm Hg; p = 0.004), 75 minutes (−4.4 mm Hg vs −1.1 mm Hg; p = 0.042), and 180 minutes (−3.4 mm Hg vs +0.0 mm Hg; p = 0.042).

When elderly patients (≥70 years) were considered the same pattern of response was found. In summary, first-dose hypotension is not negligible on initiation of therapy with ACE inhibitors in heart failure patients with low ejection fraction. Perindopril results in significantly less reduction in blood pressure and a lower incidence of symptomatic or asymptomatic hypotensive episodes and allows a safer start of therapy than captopril in heart failure patients.