DIFFERENCE IN INCIDENCE OF COUGH INDUCED BY IMIDAPRIL AND RAMIPRIL: ROLE OF PROSTAGLANDIN SYNTHESIS INHIBITION: PP.33.312

Abstract

It has been reported that the ACE-inhibitor related cough is less with imidapril than with some other ACE-inhibitors. Aim of this study was to evaluate whether treatment with imidapril reduce cough induced by ramipril and to evaluate the effect of addition of indomethacin, a known inhibitor of prostaglandins synthesis, to the 2 ACE-inhibitors on cough frequency and intensity. After 1 week placebo period 84 hypertensive patients who developed cough during chronic ramipril treatment were randomized to ramipril 10 mg or imidapril 20 mg for 8 weeks. Subsequently patients still complaining cough continued the respective ACE-inhibitor treatment, but in each arm they were allocated to receive also indomethacin 50 mg twice daily or placebo twice daily for 4 weeks according to a double masked, double dummy, cross-over design. At the end of each phase of the study cough was assessed by means of a self-administrated questionnaire with an ordinal 10-point visual analogue scale for rating daily cough intensity and frequency. At the end of the 8 weeks monotherapy phase 41 of 42 (98%) patients randomized to ramipril complained cough, while among the patients randomized to imidapril cough was complained by 23 of the 42 patients (55%), the difference between the 2 groups being statistically significant (p < 0.01). Indomethacin addition eliminated cough in 20% of patients in ramipril group and in 22% of patients in imidapril group while reduced cough intensity and frequency in 51% of patients in ramipril group and in 52% of patients in imidapril group; no significant difference was observed between the 2 treatment groups. These results indicate that incidence of cough is lower with imidapril than with ramipril and that prostaglandins play a role in the cough induced by ACE-inhibitors. The finding that the effect of indomethacin is the same with the 2 ACE-inhibitors suggests that the lower incidence of cough observed with imidapril is mediated by same mechanism independent of prostaglandin synthesis.