METHODS

Design:

3-component randomised, placebo controlled trial (Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity [CHARM] study).

Allocation:

concealed.*

Blinding:

blinded (clinicians, patients, data collectors, outcome assessors, monitoring committee, manuscript writers, and data analysts).*

Follow up period:

median 37.7 months.

Setting:

618 centres in 26 countries.

Patients:

7601 patients who were ⩾18 years of age and had symptomatic CHF (New York Heart Association class II–IV) for ⩾4 weeks. Major exclusion criteria included serum creatinine ⩾265 μmol/l; serum potassium ⩾5.5 mmol/l; bilateral renal artery stenosis; symptomatic hypotension; critical aortic or mitral stenosis; myocardial infarction, stroke, or open heart surgery in the previous 4 weeks; use of an ARB in the previous 2 weeks; other serious disease likely to limit 2 year survival; and potential for pregnancy. Patients were enrolled in 1 of 3 component trials: CHARM-Added involved patients with left ventricular ejection fraction (LVEF) ⩽40% who were being treated with an angiotensin converting enzyme (ACE) inhibitor for ⩾30 days (n = 2548); CHARM-Alternative involved patients with LVEF ⩽40% who were intolerant of ACE inhibitors (n = 2028); …