Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum

Lund, L. H. et al. (2018) Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum. European Journal of Heart Failure, 20(8), pp. 1230-1239. (doi: 10.1002/ejhf.1149) (PMID:29431256)

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Aims: We tested the hypothesis that candesartan improves outcomes in heart failure (HF) with mid-range ejection fraction [HFmrEF; ejection fraction (EF) 40–49%]. Methods and results: In 7598 patients enrolled in the CHARM Programme (HF across the spectrum of EF), we assessed characteristics, outcomes and treatment effect of candesartan according to EF. Patients with HFmrEF (n = 1322, 17%) were similar to those with HF with reduced EF (HFrEF; n = 4323, 57%) with respect to some characteristics, and intermediate between HFrEF and HF with preserved EF (HFpEF; n = 1953, 26%) with respect to others. Over a mean follow-up of 2.9 years, the incidence rates for the primary outcome of cardiovascular death or HF hospitalization were 15.9, 8.5 and 8.9 per 100 patient-years in HFrEF, HFmrEF and HFpEF. In adjusted analyses, the rates of the primary outcome declined with increasing EF up to 50%. For treatment effect, the incidence rates for the primary outcome for candesartan vs. placebo were 14.4 vs. 17.5 per 100 patient-years in HFrEF [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75–0.91; P < 0.001], 7.4 vs. 9.7 per 100 patient-years in HFmrEF (HR 0.76, 95% CI 0.61–0.96; P = 0.02), and 8.6 vs. 9.1 per 100 patient-years in HFpEF (HR 0.95, 95% CI 0.79–1.14; P = 0.57). For recurrent HF hospitalization, the incidence rate ratios were 0.68 in HFrEF (95% CI 0.58–0.80; P < 0.001), 0.48 in HFmrEF (95% CI 0.33–0.70; P < 0.001), and 0.78 in HFpEF (95% CI 0.59–1.03; P = 0.08). With EF as a continuous spline variable, candesartan significantly reduced the primary outcome until EF well over 50% and recurrent HF hospitalizations until EF well over 60%. Conclusion: Candesartan improved outcomes in HFmrEF to a similar degree as in HFrEF. ClinicalTrials.gov: CHARM Alternative NCT00634400, CHARM Added NCT00634309, CHARM Preserved NCT00634712

Item Type:Articles
Additional Information:The CHARM Programme was funded and sponsored by AstraZeneca. This post-hoc analysis did not receive funding from AstraZeneca. L.H.L. was supported by grants for a broad HFpEF research program from the Swedish Research Council (grant 2013-23897-104604-23), the Swedish Heart Lung Foundation (grant 20150063) and the Stockholm County Council (grants 20090556 and 20110120).
Glasgow Author(s) Enlighten ID:Jhund, Dr Pardeep and McMurray, Professor John
Authors: Lund, L. H., Claggett, B., Liu, J., Lam, C. S., Jhund, P. S., Rosano, G. M., Swedberg, K., Yusuf, S., Granger, C. B., Pfeffer, M. A., McMurray, J. J.V., and Solomon, S. D.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:European Journal of Heart Failure
ISSN (Online):1879-0844
Published Online:12 February 2018
Copyright Holders:Copyright © 2018 The Authors and European Society of Cardiology
First Published:First published in European Journal of Heart Failure 20(8): 1230-1239
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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