Cough‐Challenge Trial with a New Angiotensin‐Converting Enzyme Inhibitor, Imidapril

Abstract

This study was conducted to examine whether imidaprilat, an active diacid of the angiotensin-converting enzyme (ACE) inhibitor imidapril, preferentially inhibits angiotensin I degradation rather than bradykinin degradation, and whether imidapril is less active than other ACE inhibitors in inducing cough in patients with hypertension. The effect of imidaprilat on the inhibition of pressor response to angiotensin I and augmentation of depressor response to bradykinin was compared with that of enalaprilat and captopril in anesthetized rats. To determine the incidence of cough associated with imidapril, patients with a history of ACE inhibitor-induced dry cough were enrolled in a randomized, open-labeled, crossover trial with two 6-week periods to be treated with imidapril or amlodipine, a calcium-channel blocker. The recurrence of cough was assessed during both treatments. In the animal study, there were no significant differences in the ratio of inhibition of pressor response to angiotensin I and the augmentation of depressor response to bradykinin among the ACE inhibitors. In the cough-challenge trial, a total of 60 patients with hypertension were enrolled in the study. Cough and cough related symptoms recurred in 98.3% of the patients (59/ 60) during imidapril therapy. In contrast, only two patients reported cough during treatment with amlodipine. These results indicate that imidapril has no selectivity in inhibiting angiotensin I- and bradykinin-degradation in rats, and that clinically it is not different from other ACE inhibitors in inducing cough in patients with hypertension.

Efficacy and Safety of Imidapril in Patients with Essential Hypertension: A Double-Blind Comparison with Captopril

“…Recently, in a multicenter, double-blind, cross-over study, Saruta et al [9]also found that 52.8% of the patients with an enalapril-associated cough did not develop a cough after switching to imidapril, while all of the patients with an imidapril-associated cough developed a cough after switching to enalapril. In contrast, Shionoiri et al [13]observed that 98.3% of the patients with an ACE inhibitor-induced cough developed cough-related symptoms after receiving imidapril. They stressed that imidapril is not different from other ACE inhibitors in inducing a cough.…”

Angiotensin‐converting enzyme inhibitor induced cough compared with placebo, and other antihypertensives: A systematic review, and network meta‐analysis

“…The studies included participants from a wide range of medical conditions including hypertension, transient ischemic attack, coronary artery disease, proteinuria, heart failure, and organ transplant. The basic characteristics of the studies are in Table 1 15–149 . A total of 44 RCT compared ACEI with placebo, 68 RCT with ARB, and 35 RCT with CCB.…”