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New Competition in the Realm of Renin—Angiotensin Axis Inhibition; the Angiotensin II Receptor Antagonists in Congestive Heart Failure

OBJECTIVE: To critically review the studies comparing angiotensin II (AgII) receptor antagonists with placebo or angiotensin-converting enzyme (ACE) inhibitors in patients with congestive heart failure (CHF). DATA SOURCES: A MEDLINE search (1988 to January 2000) was used to identify pertinent literature. Additional references were also retrieved from selected articles. STUDY SELECTION: As most published CHF studies were performed with candesartan and losartan, these agents are the main focus of this article. However, all identified comparative clinical studies were reviewed and included, regardless of the agent used. DATA SYNTHESIS: AgII receptor antagonists inhibit the effects of AgII at its sub-type 1 receptor, independently of AgIIs synthesis pathway. They present a hemodynamic profile similar to that of ACE inhibitors, without reflex neurohormonal activation. They have been shown to be at least as effective as ACE inhibitors in improving symptoms, exercise capacity, and New York Heart Association functional class in CHF patients. Although the ELITE (Evaluation of Losartan in the Elderly) trial suggested that losartan improved survival compared with captopril, this study was not designed to look at mortality. ELITE-II, an adequately powered study, showed no difference in mortality rates between patients taking captopril and those taking losartan. The combination of AgII receptor antagonists and ACE inhibitors provides additional benefit on blood pressure lowering and prevention of ventricular remodeling. AgII receptor antagonists are well tolerated, with an incidence of adverse effects similar to or lower than that of ACE inhibitors. Their lack of effect on bradykinin degradation might explain their lower incidence of cough. CONCLUSIONS: The data cumulated thus far in patients with CHF highlight that ACE inhibitors must remain the treatment of choice and that AgII receptor antagonists may be considered as an acceptable alternative for patients who are intolerant to ACE inhibitors.