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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.
Lancet 2003; 362(9386):772-6Lct

Abstract

BACKGROUND

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.

METHODS

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.

FINDINGS

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.

INTERPRETATION

Candesartan was generally well tolerated and reduced cardiovascular mortality and morbidity in patients with symptomatic chronic heart failure and intolerance to ACE inhibitors.

Authors+Show Affiliations

Division of Cardiology, Duke University Medical Center, Durham, NC 27710, USA. grang001@mc.duke.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

13678870

Citation

Granger, Christopher B., et al. "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." Lancet (London, England), vol. 362, no. 9386, 2003, pp. 772-6.
Granger CB, McMurray JJ, Yusuf S, et al. 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. Lancet. 2003;362(9386):772-6.
Granger, C. B., McMurray, J. J., Yusuf, S., Held, P., Michelson, E. L., Olofsson, B., ... Swedberg, K. (2003). 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. Lancet (London, England), 362(9386), pp. 772-6.
Granger CB, et al. 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. Lancet. 2003 Sep 6;362(9386):772-6. PubMed PMID: 13678870.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Granger,Christopher B, AU - McMurray,John J V, AU - Yusuf,Salim, AU - Held,Peter, AU - Michelson,Eric L, AU - Olofsson,Bertil, AU - Ostergren,Jan, AU - Pfeffer,Marc A, AU - Swedberg,Karl, AU - ,, PY - 2003/9/19/pubmed PY - 2003/10/28/medline PY - 2003/9/19/entrez SP - 772 EP - 6 JF - Lancet (London, England) JO - Lancet VL - 362 IS - 9386 N2 - BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: Candesartan was generally well tolerated and reduced cardiovascular mortality and morbidity in patients with symptomatic chronic heart failure and intolerance to ACE inhibitors. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/13678870/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(03)14284-5 DB - PRIME DP - Unbound Medicine ER -