Journal Article

Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial

Michelson, Eric L, Pfeffer, Marc A, Swedberg, Karl, Olofsson, Bertil, Yusuf, Salim, Held, Peter, Granger, Christopher B, McMurray, John JV, Östergren, Jan

2003

Overview

Angiotensin-converting-enzyme (ACE) inhibitors improve outcome of patients with chronic heart failure (CHF). A substantial proportion of patients, however, experience no benefit from ACE inhibitors because of previous intolerance. We aimed to find out whether candesartan, an angiotensin-receptor blocker, could improve outcome in such patients not taking an ACE inhibitor. Between March, 1999, and March, 2001, we enrolled 2028 patients with symptomatic heart failure and left-ventricular ejection fraction 40% or less who were not receiving ACE inhibitors because of previous intolerance. Patients were randomly assigned candesartan (target dose 32 mg once daily) or matching placebo. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was by intention to treat. The most common manifestation of ACE-inhibitor intolerance was cough (72%), followed by symptomatic hypotension (13%) and renal dysfunction (12%). During a median follow-up of 33·7 months, 334 (33%) of 1013 patients in the candesartan group and 406 (40%) of 1015 in the placebo group had cardiovascular death or hospital admission for CHF (unadjusted hazard ratio 0·77 [95% CI 0·67–0·89], p=0·0004; covariate adjusted 0·70 [0·60–0·81], p<0·0001). Each component of the primary outcome was reduced, as was the total number of hospital admissions for CHF. Study-drug discontinuation rates were similar in the candesartan (30%) and placebo (29%) groups. Candesartan was generally well tolerated and reduced cardiovascular mortality and morbidity in patients with symptomatic chronic heart failure and intolerance to ACE inhibitors. Published online Sept 1, 2003 http://image.thelancet.com/extras/03art7418web.pdf

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: ACE inhibitors / Aged / Anaphylaxis / Angina pectoris / Angioplasty / Angiotensin Receptor Antagonists / Angiotensin-converting enzyme inhibitors / Angiotensin-Converting Enzyme Inhibitors - adverse effects / Angiotensin-Converting Enzyme Inhibitors - therapeutic use / Antihypertensive Agents - therapeutic use / Benzimidazoles - therapeutic use / Beta blockers / Cardiac Output, Low - drug therapy / Cardiac Output, Low - epidemiology / Cardiovascular diseases / Clinical outcomes / Comorbidity / Conversion / Cough / Cough - chemically induced / Diabetes / Disease management / Drug dosages / Drug therapy / Dyspnea / Edema / Enzyme inhibitors / Enzymes / Female / Follow-Up Studies / Heart / Heart attacks / Heart diseases / Heart failure / Heart Failure - drug therapy / Heart Failure - epidemiology / Humans / Hypotension / Hypotension - chemically induced / Intolerance / Kidney Diseases - chemically induced / Laboratories / Male / Morbidity / Mortality / Motivation / Patient safety / Patients / Peptidyl-dipeptidase A / Renal function / Stroke / Tetrazoles - therapeutic use / Treatment Outcome / Ventricle / Ventricular Dysfunction, Left - drug therapy / Ventricular Dysfunction, Left - epidemiology