EFFECT OF DOSE ADJUSTMENT ON ENALAPRIL-INDUCED COUGH AND THE RESPONSETO INHALED CAPSAICIN

1 In nine hypertensive patients with enalapril-induced cough the effec t of altering the dose of enalapril on subjective cough and the cough response to inhaled capsaicin was examined in a random single-blind ba lanced cross-over study. They received three doses of enalapril each f or 3 weeks; the dose at entry (mean 10 mg daily); double this dose (me an 20 mg daily); and half this dose (mean 5 mg daily). 2 The cough res ponse to inhaled capsaicin was also measured in two control groups: hy pertensive patients on long-term enalapril treatment with no cough (n = 18), and hypertensive patients taking nifedipine (n = 17). 3 In pati ents with enalapril-induced cough there were significant dose-response s for enalapril as regards severity of cough (P < 0.05) and night time waking by cough (P < 0.05), but not for frequency of cough. Although the cough was less severe (P < 0.002) and caused less night time wakin g (P < 0.03) on the lowest dose of enalapril (mean 5 mg daily) it did not disappear completely in any patient. 4 The sensitivity to inhaled capsaicin did not differ significantly on the three doses of enalapril . The relative potency of capsaicin on enalapril 20 mg compared with e nalapril 5 mg was 1.0 (95% CI 0.4-2.2). The wide confidence limits ind icate that an important dose-dependent shift in capsaicin sensitivity is not excluded. 5 The sensitivity to inhaled capsaicin differed signi ficantly between patients with enalapril-induced cough and both contro l groups. The relative potency of capsaicin was 0.2 (95% CI 0.1-0.4, P < 0.001) in patients taking nifedipine, and 0.4 (95% CI 0.2-0.8, P < 0.005) in patients taking enalapril who had no cough, when compared wi th patients with enalapril-induced cough. 6 The dose-response for caps aicin was shifted significantly to the left in patients on enalapril w ho had no cough when compared with patients taking nifedipine (relativ e potency 0.5, 95% CI 0.3-1.0, P < 0.05). 7 In patients with enalapril -induced cough reducing the dose improves the severity of cough and ni ght time waking, but this may be of limited value as the cough persist ed to some degree in all patients. 8 The enhanced sensitivity to capsa icin in patients taking enalapril who had no cough suggests that ACE i nhibitors may alter the cough reflex in all patients, with those who d evelop cough representing the extreme of this general shift. This hypo thesis needs to be tested in a larger prospective study.