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

Lund, LH; Claggett, B; Liu, J; Lam, CS; Jhund, PS; Rosano, GM; Swedberg, K; Yusuf, S; Granger, CB; Pfeffer, MA; et al. Lund, LH; Claggett, B; Liu, J; Lam, CS; Jhund, PS; Rosano, GM; Swedberg, K; Yusuf, S; Granger, CB; Pfeffer, MA; McMurray, JJV; Solomon, SD (2018) Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum. Eur J Heart Fail, 20 (8). pp. 1230-1239. ISSN 1879-0844 https://doi.org/10.1002/ejhf.1149
SGUL Authors: Rosano, Giuseppe Massimo Claudio

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Abstract

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: Article
Additional Information: This is the peer reviewed version of the following article: 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. and Solomon, S. D. (2018), Heart failure with mid‐range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum. Eur J Heart Fail, 20: 1230-1239, which has been published in final form at https://doi.org/10.1002/ejhf.1149. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Keywords: Angiotensin receptor blocker, Candesartan, Heart failure, Mid-range ejection fraction, Outcomes, Preserved ejection fraction, Randomized controlled trial, Aged, Angiotensin II Type 1 Receptor Blockers, Benzimidazoles, Cause of Death, Europe, Female, Heart Failure, Humans, Male, Prognosis, Registries, Risk Factors, Stroke Volume, Survival Rate, Tetrazoles, Treatment Outcome, United States, Humans, Tetrazoles, Benzimidazoles, Angiotensin II Type 1 Receptor Blockers, Stroke Volume, Prognosis, Treatment Outcome, Registries, Cause of Death, Survival Rate, Risk Factors, Aged, United States, Europe, Female, Male, Heart Failure, 1102 Cardiovascular Medicine And Haematology, Cardiovascular System & Hematology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Eur J Heart Fail
ISSN: 1879-0844
Language: eng
Dates:
DateEvent
3 August 2018Published
12 February 2018Published Online
8 January 2018Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
2013‐23897‐104604‐23Swedish Research Council Formashttp://dx.doi.org/10.13039/501100001862
20150063Swedish Heart Lung FoundationUNSPECIFIED
20090556Stockholm County CouncilUNSPECIFIED
20110120Stockholm County CouncilUNSPECIFIED
PubMed ID: 29431256
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/111201
Publisher's version: https://doi.org/10.1002/ejhf.1149

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