Effects of amlodipine, nifedipine GITS, and indomethacin on angiotensin-converting enzyme inhibitor-induced cough: A randomized, placebo-controlled, double-masked, crossover study

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Prostaglandins (PGs) are thought to play a role in the genesis of cough induced by angiotensin-converting enzyme (ACE) inhibitors, whereas inhibition of PG synthesis can reduce or abolish the incidence of this side effect. Experimental and clinical data suggest that nifedipine, a dihydropyridine calcium channel blocker, can inhibit PG synthesis. Therefore, the aim of the present study was to determine whether treatment with amlodipine would also reduce cough induced by an ACE inhibitor and to compare the efficacy of amlodipine with that of indomethacin, a known inhibitor of PG synthesis. Thirty-three patients with hypertension who developed cough during chronic benazepril therapy were allocated randomly to receive slow-release nifedipine gastrointestinal therapeutic system (GITS) 30 mg once daily, amlodipine 5 mg once daily, indomethacin 50 mg twice daily, or placebo twice daily for 2 weeks. This was according to a double-masked, double-dummy, crossover, Latin square design. At the end of each phase, 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. Indomethacin eliminated or markedly reduced cough induced by the ACE inhibitor, whereas nifedipine GITS and amlodipine reduced it to a lesser degree. These findings suggest that PGs play a role in cough caused by ACE inhibitors and that a dihydropyridine calcium channel blocker can reduce the occurrence of this side effect.