Cited by 2,604Heart Failure Treatment and ManagementRenin-Angiotensin System StudiesHeart rate and cardiovascular health

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

McMurray, John JV, Östergren, Jan, Swedberg, Karl, Granger, Christopher B, Held, Peter, Michelson, Eric L, Olofsson, Bertil, Yusuf, Salim, Pfeffer, Marc A·2003·The Lancet

DOI 10.1016/s0140-6736(03)14283-3

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Abstract

Background 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.Methods 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 beta 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.Findings 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 beta blocker treatment.Interpretation 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.

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Authors: McMurray, J. J., Östergren, J., Swedberg, K., Granger, C. B., Held, P., Michelson, E. L., Olofsson, B., Yusuf, S., & Pfeffer, M. A.
Affiliations: University of Glasgow (GB)
Karolinska University Hospital (SE)
Sahlgrenska University Hospital (SE)
Duke Medical Center (US)
AstraZeneca (Sweden) (SE)
AstraZeneca (United States) (US)
Hamilton Health Sciences (CA)
Brigham and Women's Hospital (US)
Corresponding author: McMurray, John JV
ORCID: McMurray, John JV
Östergren, Jan
Swedberg, Karl
Granger, Christopher B
Yusuf, Salim
Pfeffer, Marc A
Venue: The Lancet
Publisher: Elsevier BV
Published: 2003-09
Volume: 362
Issue: 9386
Pages: 767-771
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(03)14283-3
OpenAlex: W2098780362
Cited by: 2,604
References: 38
Citations by year: 2026: 8 · 2025: 15 · 2024: 46 · 2023: 52 · 2022: 58 · 2021: 60 · 2020: 98 · 2019: 82 · 2018: 66 · 2017: 103 · 2016: 108 · 2015: 118 · 2014: 122 · 2013: 126 · 2012: 153
FWCI: 122.65
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed (publishedVersion)
Funders: AstraZeneca
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
Keywords: candesartan, chronic heart failure, reduced left ventricular ejection fraction, angiotensin receptor blockers, ACE inhibitors, combination therapy, cardiovascular mortality, beta-blockers, spironolactone
MeSH terms: Adolescent, Adult, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Benzimidazoles, Biphenyl Compounds, Cardiac Output, Low, Cardiovascular Diseases, Drug Administration Schedule, Drug Therapy, Combination, Female, Follow-Up Studies, Heart Failure, Hospitalization, Humans, Male, Placebos, Tetrazoles, Comorbidity, Treatment Outcome, Ventricular Dysfunction, Left, Angiotensin Receptor Antagonists

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

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