COUGH-CHALLENGE TRIAL WITH A NEW ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR, IMIDAPRIL

This study was conducted to examine whether imidaprilat, an active dia cid of the angiotensin-converting enzyme (ACE) inhibitor imidapril, pr eferentially inhibits angiotensin I degradation rather than bradykinin degradation, and whether imidapril is less active than other ACE inhi bitors 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 th at 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, ope n-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 presser response to angiotensin I and the augmentation of depressor response t o bradykinin among the ACE inhibitors. In the cough-challenge trial, a total of 60 patients with hypertension were enrolled in the study Cou gh and cough related symptoms recurred in 98.3% of the patients (59/60 ) during imidapril therapy. In contrast, only two patients reported co ugh during treatment with amlodipine. These results indicate that imid april has no selectivity in inhibiting, angiotensin I-and bradykinin-d egradation in rats, and that clinically it is not different from other ACE inhibitors in inducing cough in patients with hypertension. (C) 1 998 The American College of Clinical Pharmacology.