Journal Article

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

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

2003

Overview

Angiotensin II type 1 receptor blockers have favourable effects on haemodynamic measurements, neurohumoral activity, and left-ventricular remodelling when added to angiotensin-converting-enzyme (ACE) inhibitors in patients with chronic heart failure (CHF). We aimed to find out whether these drugs improve clinical outcome. Between March, 1999, and November, 1999, we enrolled 2548 patients with New York Heart Association functional class II–IV CHF and left-ventricular ejection fraction 40% or lower, and who were being treated with ACE inhibitors. We randomly assigned patients candesartan (n=1276, target dose 32 mg once daily) or placebo (n=1272). At baseline, 55% of patients were also treated with β blockers and 17% with spironolactone. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was done by intention to treat. The median follow-up was 41 months. 483 (38%) patients in the candesartan group and 538 (42%) in the placebo group experienced the primary outcome (unadjusted hazard ratio 0·85 [95% CI 0·75–0·96], p=0·011; covariate adjusted p=0·010). Candesartan reduced each of the components of the primary outcome significantly, as well as the total number of hospital admissions for CHF. The benefits of candesartan were similar in all predefined subgroups, including patients receiving baseline β blocker treatment. The addition of candesartan to ACE inhibitor and other treatment leads to a further clinically important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction. Published online Sept 1, 2003 http://image.thelancet.com/extras/03art7417web.pdf

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: ACE inhibitors / Adolescent / Adult / Angina pectoris / Angioplasty / Angiotensin II / Angiotensin Receptor Antagonists / Angiotensin-converting enzyme inhibitors / Angiotensin-Converting Enzyme Inhibitors - therapeutic use / Antihypertensive Agents - therapeutic use / Benzimidazoles - therapeutic use / Cardiac arrhythmia / Cardiac Output, Low - drug therapy / Cardiac Output, Low - epidemiology / Cardiac Output, Low - mortality / Cardiovascular Diseases - mortality / Clinical outcomes / Comorbidity / Conversion / Diabetes / Disease management / Drug Administration Schedule / Drug dosages / Drug therapy / Drug Therapy, Combination / Dyspnea / Edema / Enzyme inhibitors / Enzymes / Female / Follow-Up Studies / Health risk assessment / Heart / Heart attacks / Heart diseases / Heart failure / Heart Failure - drug therapy / Heart Failure - epidemiology / Heart Failure - mortality / Hospitalization / Humans / Laboratories / Male / Morbidity / Mortality / Motivation / Patients / Peptidyl-dipeptidase A / Placebo effect / Placebos / Stroke / Subgroups / Tetrazoles - therapeutic use / Treatment Outcome / Ventricle / Ventricular Dysfunction, Left - drug therapy / Ventricular Dysfunction, Left - epidemiology / Ventricular Dysfunction, Left - mortality