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) i nhibitors 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 select ed articles. STUDY SELECTION: As most published CHF studies were performed with candesar tan and losartan, these agents are the main focus of this article. However, all identified comparative clinical studies were reviewed and included, re gardless of the agent used. DATA SYNTHESIS: AgII receptor antagonists inhibit the effects of AgII at it s sub-type 1 receptor, independently of AgII's synthesis pathway. They pres ent 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 H eart Association functional class in CHF patients. Although the ELITE (Eval uation of Losartan in the Elderly) trial suggested that losartan improved s urvival compared with captopril, this study was not designed to look at mor tality. ELITE-II, an adequately powered study, showed no difference in mort ality rates between patients taking captopril and those taking losartan. Th e combination of AgII receptor antagonists and ACE inhibitors provides addi tional benefit on blood pressure lowering and prevention of ventricular rem odeling. AgII receptor antagonists are well tolerated, with an incidence of adverse effects similar to or lower than that of ACE inhibitors. Their lac k of effect on bradykinin degradation might explain their lower incidence o f cough. CONCLUSIONS: The data cumulated thus far in patients with CHF highlight tha t ACE inhibitors must remain the treatment of choice and that AgII receptor antagonists may be considered as an acceptable alternative for patients wh o are intolerant to ACE inhibitors.