Effects of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction patients with chronic obstructive pulmonary disease in EMPHASIS-HF and RALES

Yeoh, S. E., Dewan, P. , Serenelli, M., Ferreira, J. P., Pitt, B., Swedberg, K., Veldhuisen, D. J., Zannad, F., Jhund, P. S. and McMurray, J. J.V. (2021) Effects of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction patients with chronic obstructive pulmonary disease in EMPHASIS-HF and RALES. European Journal of Heart Failure, (doi: 10.1002/ejhf.2350) (PMID:34536265) (Early Online Publication)

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Abstract

Heart failure with reduced ejection fraction (HFrEF) and chronic obstructive pulmonary disease (COPD) individually cause significant morbidity and mortality. Their coexistence is associated with even worse outcomes, partly due to suboptimal heart failure therapy, especially underutilisation of beta-blockers. Our aim was to investigate outcomes in HFrEF patients with and without COPD, and the effects of mineralocorticoid receptor antagonists (MRAs) on outcomes. Methods and results: We studied the effect of MRA therapy in a post-hoc pooled analysis of 4397 HFrEF patients in the RALES and EMPHASIS-HF trials. The primary endpoint was the composite of heart failure hospitalisation or cardiovascular death. A total of 625 (14.2%) of the 4397 patients had COPD. Patients with COPD were older, more often male, and smokers, but less frequently treated with a beta-blocker. In patients with COPD, event rates (per 100 person-years) for the primary endpoint and for all-cause mortality were 25.2 (95% confidence interval 22.1–28.7) and 17.2 (14.9–19.9), respectively, compared with 19.9 (18.8–21.1) and 12.8 (12.0–13.7) in participants without COPD. The risks of all-cause hospitalisation and sudden death were also higher in patients with COPD. The benefit of MRA, compared with placebo, was consistent in patients with or without COPD for all outcomes, e.g. hazard ratio for the primary outcome 0.66 (0.50–0.85) for COPD and 0.65 (0.58–0.73) for no COPD (interaction p = 0.93). MRA-induced hyperkalaemia was less frequent in patients with COPD. Conclusions: In RALES and EMPHASIS-HF, one-in-seven patients with HFrEF had coexisting COPD. HFrEF patients with COPD had worse outcomes than those without. The benefits of MRAs were consistent, regardless of COPD status.

Item Type:Articles
Additional Information:This work was supported by the British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217.
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ferreira, Mr Joao Pedro and Yeoh, Dr Su Ern and Jhund, Dr Pardeep and SERENELLI, Dr MATTEO and Dewan, Dr Pooja and McMurray, Professor John
Authors: Yeoh, S. E., Dewan, P., Serenelli, M., Ferreira, J. P., Pitt, B., Swedberg, K., Veldhuisen, D. J., Zannad, F., Jhund, P. S., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:European Journal of Heart Failure
Publisher:Wiley
ISSN:1879-0844
ISSN (Online):1879-0844
Published Online:18 September 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in European Journal of Heart Failure 2021
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science