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Modulation of the renin-angiotensin-aldosterone system and cough.

Author(s): Lacourciere Y, Lefebvre J

Affiliation(s): Hypertension Research Unit, Le Centre Hospitalier de l'Universite Laval, Ste-Foy, Quebec.

Publication date & source: 1995-08, Can J Cardiol., 11 Suppl F:33F-39F.

Publication type: Clinical Trial; Randomized Controlled Trial; Review

OBJECTIVES: To review the clinical features of the cough related to angiotensin-converting enzyme (ACE) inhibitor therapy, and to suggest from a prospective controlled study that angiotensin II (Ang II) receptor antagonists are not associated with this particular side effect to the same extent as observed with ACE inhibitors. DATA SOURCES: All pertinent data from reports published between 1972 and 1994 were identified through a comprehensive medical literature search. Additionally, results are presented from an international multicentre study examining the occurrence of cough in 135 patients with mild to moderate hypertension, with a history of ACE inhibitor-related cough, who were randomly given either losartan (a type I Ang II receptor antagonist), lisinopril (an ACE inhibitor), or hydrochlorothiazide (a thiazide diuretic). STUDY SELECTION: More than 500 articles were identified; those reporting frequency, characterization, mechanism and treatment of ACE inhibitor-induced cough were chosen. For the multicentre study, men and women with uncomplicated hypertension and a history of ACE inhibitor dry cough were eligible to enter, provided their cough had completely resolved. DATA EXTRACTION AND SYNTHESIS: Relevant information from published case reports, abstracts, postmarketing surveillance studies, hospital series and randomized controlled trials was examined and synthesized. In a recent multicentre study in which patients with a prior history of ACE inhibitor-related cough were randomized into three treatment groups, the percentage of patients with a dry cough was significantly higher in the lisinopril group (72%) than in the losartan (29%) or the hydrychlorothiazide (34%) groups. CONCLUSIONS: Ang II receptor antagonists are novel pharmacological agents that block the renin-angiotensin-aldosterone system at the level of tissue receptors, without affecting interdependant systems. Results from the prospective study reported in the present manuscript demonstrate that the higher specificity of the type I Ang II receptor antagonist losartan is associated with a significantly lower incidence of cough than seen with ACE inhibitors. Losartan thus represents a potential new treatment for hypertensive patients in whom ACE inhibition or Ang II receptor antagonists are indicated, but who develop cough with ACE inhibitors.

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