Incidence of cough induced by imidapril in patients with hypertension with enalapril-associated cough

The purpose of this study was to determine the incidence of cough and changes in blood levels of prostaglandin after replacement with imidapril in patients with hypertension with a history of enalapril-induced cough. In 18 patients (3 men and 15 women), enalapril decreased mean aortic blood pressure statistically significantly from 124 +/- 14 mm Hg to 104 +/- 12 mm Hg. Enalapril had to be withdrawn because of the development of irritating dry cough during this therapy. After verifying that the cough had disappeared following withdrawal of enalapril, we began medication with imidapril 5 mg in 15 (83%) of the 18 patients (1 patient had gastrointestinal irritation and 2 were lost to follow-up), resulting in a statistically significant decrease in mean aortic blood pressure from 128 +/- 16 mm Hg to 108 +/- 10 mm Hg. The cough profile during imidapril therapy was compared with that during enalapril therapy. During the follow-up period (31 +/- 13 weeks), 5 patients (group 1, mean age 61 +/- 17 years; 5 women) had to stop taking imidapril because of irritating cough, 6 patients had no cough (group 2, mean age 63 +/- 12 years; 1 man, 5 women), and 4 patients who had a dry cough less severe than that during enalapril therapy but that did not preclude their continuing use of imidapril (group 3, mean age 69 +/- 12 years; 2 men, 2 women). Imidapril had no effect on the plasma concentration of either prostaglandin F-2 alpha or thromboxane B-2 in any group, but the prostaglandin E-2 concentrations showed a statistically significant increase in groups 2 and 3. Sulindac, a prostaglandin synthesis inhibitor, was administered to 3 patients in group I and 2 patients in group 3 selected at random. Sulindac abolished the cough completely in 4 patients and was partially effective in 1 patient. Imidapril could be used in 67% (groups 2 and 3) of patients with enalapril-induced cough. We conclude that local, not systemic, activation of the prostaglandin cascade is responsible for the development of this side effect of angiotensin-converting enzyme (ACE) inhibitors. Although this was an uncontrolled, open-label study, our results provide a potential new treatment with imidapril for patients with hypertension when ACE inhibitors are indicated but cough develops with their use.