| Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. | |
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MedLine Citation:
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PMID: 13678868 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Patients with chronic heart failure (CHF) are at high risk of cardiovascular death and recurrent hospital admissions. We aimed to find out whether the use of an angiotensin-receptor blocker could reduce mortality and morbidity. METHODS: In parallel, randomised, double-blind, controlled, clinical trials we compared candesartan with placebo in three distinct populations. We studied patients with left-ventricular ejection fraction (LVEF) 40% or less who were not receiving angiotensin-converting-enzyme inhibitors because of previous intolerance or who were currently receiving angiotensin-converting-enzyme inhibitors, and patients with LVEF higher than 40%. Overall, 7601 patients (7599 with data) were randomly assigned candesartan (n=3803, titrated to 32 mg once daily) or matching placebo (n=3796), and followed up for at least 2 years. The primary outcome of the overall programme was all-cause mortality, and for all the component trials was cardiovascular death or hospital admission for CHF. Analysis was by intention to treat. FINDINGS: Median follow-up was 37.7 months. 886 (23%) patients in the candesartan and 945 (25%) in the placebo group died (unadjusted hazard ratio 0.91 [95% CI 0.83-1.00], p=0.055; covariate adjusted 0.90 [0.82-0.99], p=0.032), with fewer cardiovascular deaths (691 [18%] vs 769 [20%], unadjusted 0.88 [0.79-0.97], p=0.012; covariate adjusted 0.87 [0.78-0.96], p=0.006) and hospital admissions for CHF (757 [20%] vs 918 [24%], p<0.0001) in the candesartan group. There was no significant heterogeneity for candesartan results across the component trials. More patients discontinued candesartan than placebo because of concerns about renal function, hypotension, and hyperkalaemia. INTERPRETATION: Candesartan was generally well tolerated and significantly reduced cardiovascular deaths and hospital admissions for heart failure. Ejection fraction or treatment at baseline did not alter these effects. |
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Authors:
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Marc A Pfeffer; Karl Swedberg; Christopher B Granger; Peter Held; John J V McMurray; Eric L Michelson; Bertil Olofsson; Jan Ostergren; Salim Yusuf; Stuart Pocock; |
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Publication Detail:
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Type: Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Lancet Volume: 362 ISSN: 1474-547X ISO Abbreviation: Lancet Publication Date: 2003 Sep |
Date Detail:
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Created Date: 2003-09-18 Completed Date: 2003-10-27 Revised Date: 2009-11-23 |
Medline Journal Info:
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Nlm Unique ID: 2985213R Medline TA: Lancet Country: England |
Other Details:
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Languages: eng Pagination: 759-66 Citation Subset: AIM; IM |
Affiliation:
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Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. mpfeffer@rics.bwh.harvard.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Angiotensin-Converting Enzyme Inhibitors / therapeutic use Antihypertensive Agents / therapeutic use* Benzimidazoles / therapeutic use* Cardiac Output, Low / drug therapy, mortality Cardiovascular Diseases / mortality Cause of Death Double-Blind Method Female Follow-Up Studies Heart Failure / drug therapy*, mortality* Humans Male Placebos Receptors, Angiotensin / antagonists & inhibitors Tetrazoles / therapeutic use* Treatment Outcome |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Benzimidazoles; 0/Placebos; 0/Receptors, Angiotensin; 0/Tetrazoles; 139481-59-7/candesartan |
| Comments/Corrections | |
Comment In:
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Curr Hypertens Rep. 2004 Feb;6(1):47
[PMID:
14972091
]
Lancet. 2003 Nov 15;362(9396):1675-6; author reply 1678-9 [PMID: 14630453 ] Lancet. 2003 Nov 15;362(9396):1676; author reply 1678-9 [PMID: 14630454 ] Lancet. 2003 Nov 15;362(9396):1676-7; author reply 1678-9 [PMID: 14630455 ] Lancet. 2003 Nov 15;362(9396):1677-8; author reply 1678-9 [PMID: 14630457 ] Lancet. 2003 Nov 15;362(9396):1678; author reply 1678-9 [PMID: 14630459 ] Lancet. 2003 Nov 15;362(9396):1679 [PMID: 14630460 ] Lancet. 2003 Sep 6;362(9386):754-5 [PMID: 13678864 ] ACP J Club. 2004 Mar-Apr;140(2):32-3 [PMID: 15122853 ] Curr Hypertens Rep. 2004 Feb;6(1):46 [PMID: 14972090 ] |
Erratum In:
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Lancet. 2009 Nov 21-2009 Nov 27;(9703):1744 |
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