Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors

Background Many patients with congestive heart failure do not receive the b enefits of angiotensin-converting enzyme (ACE) inhibitors because of intole rance. We sought to determine the tolerability of an angiotensin II recepto r blocker, candesartan cilexetil, among patients considered intolerant of A CE inhibitors. Methods patients with CHF, left ventricular ejection Fraction less than 35% , and history of discontinuing an ACE inhibitor because of intolerance unde rwent double-blind randomization in a 2:1 ratio to receive candesartan (n = 179) or a placebo (n = 91). The initial dosage of candesartan was 4 mg/d; the dosage was increased to 16 mg/d if the drug was tolerated. A history of intolerance of ACE inhibitor was attributed to cough (67% of patients), hy potension (15%), or renal dysfunction (11%). Results The study drug was continued for 12 weeks by 82.7% of patients who received candesartan versus 86.8% of patients who received the placebo. Thi s 4.1% greater discontinuation rate with active therapy was not significant ; the 95% confidence interval ranged from 4.8% more discontinuation with pl acebo to 13% more with candesartan. Titration to the 16 mg target dose was possible for 69% of patients who received candesartan versus 84% of those w ho received the placebo. Frequencies of death and morbidity were not signif icantly different between the candesartan and placebo groups (death 3.4% an d 3.3%, worsening heart failure 8.4% and 13.2%, myocardial infarction 2.8% and 5.5%, all-cause hospitalization 12.8% and 18.7%, and death or hospitali zation for heart failure 11.7% and 14.3%). Conclusions Candesartan was well tolerated by this population. The effect o f candesartan on major clinical end points, including death, remains to be determined.