MODULATION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM AND COUGH

OBJECTIVES: To review the clinical features of the cough related to an giotensin converting enzyme (ACE) inhibitor therapy, and to suggest fr om a prospective controlled study that angiotensin II (ANG II) recepto r antagonists are not associated with this particular side effect to t he same extent as observed with ACE inhibitors. DATA SOURCES: All pert inent data from reports published between 1972 and 1994 with identifie d through a comprehensive medical literature search. Additionally, res ults are presented from an international multicentre study examining t he occurrence of cough in 135 patients with mild to moderate hypertens ion, with a history of ACE inhibitor-related cough, who were given los artan (a type I Ang II receptor antagonist), lisinopril (an ACE inhibi tor), or hydrochlorothiazide (a thiazide diuretic). STUDY SELECTION: M ore than 500 articles were identified; those reporting frequency, char acterization, mechanism and treatment of ACE inhibitor-induced cough w ere chosen. For the multicentre study, men and women were uncomplicate d hypertension and a history of ACE inhibitor dry cough were eligible to enter, provided their cough had completely resolved. DATA EXTRACTIO N AND SYNTHESIS: Relevant information from published case reports, abs tracts, postmarketing surveillance studies, hospital series and random ized controlled trials was examined and synthesized. In a recent multi centre study in which patients with a prior history of ACE inhibitor-r elated cough were randomized into three treatment groups, the percenta ge of patients with a dry cough was significantly higher in the lisino pril group (72%) than in the losartan (29%) or the hydrychlorothiazide (34%) groups. CONCLUSIONS: Ang II receptor antagonists are novel phar macological agents that block the renin-angiotensin aldosterone system at the level of tissue receptors, without affecting interdependent sy stems. Results from the prospective study reported in the present manu script demonstrate that the higher specificity of the type I Ang II re ceptor antagonist losartan is associated with a significantly lower in cidence of cough than seen with ACE inhibitors. Losartan thus represen ts a potential new treatment for hypertensive patients in whom ACE inh ibition or Ang II receptor antagonists are indicated, but who develop cough with ACE inhibitors.