Clinical trials of angiotensin receptor blockers in heart failure: what do we know and what will we learn?

Although interruption of the renin-angiotensin system with angiotensin converting enzyme (ACE) inhibitors has evolved as the therapy of choice in heart failure based on large-scale morbidity and mortality clinical studies, treatment with angiotensin type 1 receptor blockers (ARB) offers an alternative and potentially superior method of treating this condition. Early pilot studies were quite promising; however, two well designed, large-scale trials have shown that the reduction in heart failure mortality with ARB is not significantly different from the reduction with ACE inhibitors. Possible reasons for lack of ARB superiority include insufficient dosing of ARB, differences in effects mediated through angiotensin II type 2 receptors, interaction with β-blockers, and bradykinin-mediated effects specific to ACE inhibitors. The ACE inhibitors remain the current therapy of choice in treating heart failure until further outcomes trial data become available; however, ARB are a reasonable alternative in patients intolerant of ACE inhibitors.