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European Heart Journal Advance Access published online on April 14, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn153
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure

An analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme

Michael R. MacDonald1, Mark C. Petrie1, Fumi Varyani2, Jan Östergren3, Eric L. Michelson4, James B. Young5, Scott D. Solomon6, Christopher B. Granger7, Karl Swedberg8, Salim Yusuf9, Marc A. Pfeffer6, John J.V. McMurray for the CHARM Investigators2,*

1 Glasgow Royal Infirmary, Glasgow, UK
2 BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
3 Department of Medicine, Karolinska University Hospital Solna, Stockholm, Sweden
4 AstraZeneca LP, Wilmington, DE, USA
5 Cleveland Clinic Foundation, Cleveland, OH, USA
6 Brigham & Women's Hospital, Boston, MA, USA
7 Duke University Medical Center, Durham, NC, USA
8 Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
9 Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada

Received 23 September 2007; revised 25 February 2008; accepted 20 March 2008.

* Corresponding author. Tel: +44 141 330 3479, Fax: +44 141 330 6955, Email: j.mcmurray{at}bio.gla.ac.uk

Aims: To determine whether the risk of adverse cardiovascular (CV) outcomes associated with diabetes differs in patients with low and preserved ejection fraction (EF) heart failure (HF).

Methods and results: We analysed outcomes in the Candesartan in Heart failure—Assessment of Reduction in Mortality and morbidity (CHARM) programme which randomized 7599 patients with symptomatic HF and a broad range of EF. The prevalence of diabetes was 28.3% in patients with preserved EF (>40%) and 28.5% in those with low EF (≤40%). Diabetes was associated with a greater relative risk of CV death or HF hospitalization in patients with preserved EF [hazard ratio (HR) 2.0 (1.70–2.36)] than in patients with low EF [HR 1.60 (1.44–1.77); interaction test P = 0.0009]. For all-cause mortality, the risk conferred by diabetes was similar in both low and preserved EF groups. The effect of candesartan in reducing CV morbidity and mortality outcomes was not modified by having diabetes at baseline (P = 0.09 test for interaction).

Conclusion: Diabetes was an independent predictor of CV morbidity and mortality in patients with HF, regardless of EF. The relative risk of CV death or HF hospitalization conferred by diabetes was significantly greater in patients with preserved when compared with those with low EF HF.

Key Words: Heart failure • Diabetes


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