Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial
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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The coexistence of type 2 diabetes mellitus and heart failure, either with reduced or preserved ejection fraction, is frequent, affecting 30-40% of patients.
“The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients)”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [38]
In clinical trials of chronic HF patients, the prevalence of T2DM was around 30%, irrespective of HF phenotype.
“In clinical trials of chronic HF patients, the prevalence of T2DM was around 30%, irrespective of HF phenotype (i.e.HFrEF and HFpEF) (Table 3).31 -48”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [38]
The highest prevalence of T2DM was seen in trials of acute HF, around 40%.
“The highest prevalence of T2DM was seen in trials of acute HF (around 40%).”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [38]
In patients with congestive heart failure, including diabetic subgroups, ARBs reduce major CVD outcomes.
“In patients with congestive heart failure (CHF), including diabetic subgroups, ARBs have been shown to reduce major CVD outcomes (175–178), and in type 2 patients with significant nephropathy, ARBs were superior to calcium channel blockers for reducing heart failure (179–181).”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [177]
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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
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 362
- Issue
- 9386
- Pages
- 767-771
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- 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
- 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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