Difference in incidence of cough induced by imidapril and ramipril: Role of prostaglandin synthesis inhibition

Aim of this study was to evaluate whether treatment with imidapril reduced cough induced by ramipril. The effect of adding indomethacin, a known inhibitor of prostaglandin (PG) synthesis, to the two ACE-inhibitors (ACE-I) on cough frequency and intensity was also assessed. After a 2-week placebo period, 97 hypertensive patients who developed cough during ramipril treatment were randomized to ramipril 10 mg or imidapril 20 mg for 8 weeks. Thereafter, patients still complaining cough continued the respective ACE-inhibitor treatment, but in each arm they were allocated to receive also indomethacin 50 mg or placebo for 4 weeks according to a double-blind, cross-over design. At the end of each phase of the study cough was assessed by means of a self-administered questionnaire with an ordinal 10-point visual analogue scale for rating daily cough intensity and frequency. At the end of the 8-week monotherapy phase, cough was complained by 48 of 49 (98%) patients randomized to ramipril and by 24 of the 48 (50%) patients randomized to imidapril, the difference between the two groups being significant (P < 0.01). Indomethacin significantly reduced the mean score for cough intensity and frequency (P < 0.01) in both ramipril and imidapril treated patients, with no difference between the two groups. These results indicate that the incidence of cough recurrence is lower with imidapril than with ramipril. The finding that the effect of indomethacin on cough frequency and intensity is the same in the two treatment groups suggests that the lower incidence of cough observed with imidapril might be mediated by some mechanism independent of PG synthesis.