Angiotensin II receptor antagonists in the treatment of heart failure: background to and design of the CHARM study

While angiotensin-converting enzyme (ACE) inhibitors are established agents for the treatment of hypertension and heart failure, in contrast the angiotensin II receptor antagonists (AIIRAs) have failed to demonstrate more than equivalence in randomised clinical trials. Trials such as ELITE II are criticised on the grounds that the dose used of losartan (50 mg) may have been sub-optimal. In ValHeFT, valsartan was shown to be superior to placebo only in patients who did not also receive a beta blocker. The ambiguity of response of AIIRAs in such trials will hopefully be clarified in CHARM, a large, placebo-controlled study which will assess the effects of candesartan in heart failure patients with either reduced ejection fractions in addition to an ACE inhibitor, and in those intolerant to an ACE inhibitor, as well as in patients with preserved ventricular function (diastolic heart failure) not on an ACE inhibitor. The design of the study is discussed.