Mineralocorticoid receptor antagonists, blood pressure, and outcomes in heart failure with reduced ejection fraction

Serenelli, M. et al. (2020) Mineralocorticoid receptor antagonists, blood pressure, and outcomes in heart failure with reduced ejection fraction. JACC: Heart Failure, 8(3), pp. 188-198. (doi: 10.1016/j.jchf.2019.09.011) (PMID:31926854) (PMCID:PMC7086149)

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Objectives: The purpose of this study was to investigate the effects of mineralocorticoid receptor antagonists (MRAs) on systolic blood pressure (SBP) and outcomes according to baseline SBP in patients with heart failure with reduced ejection fraction (HFrEF). Background: MRAs are greatly underused in patients with HFrEF, often because of fear of adverse events. Concern about hypotension has been raised by the demonstration that MRAs are particularly effective treatment for resistant hypertension. Methods: The effect of MRA therapy was studied in 4,396 patients with HFrEF randomized in the RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trials. Results: Mean SBP change from baseline to 6 months was +1.4 ± 18.1 mm Hg in the placebo group and −1.2 ± 17.9 mm Hg in the MRA group. The between-treatment difference was 2.6 mm Hg (95% confidence interval [CI]: 1.5 to 3.6; p < 0.001). All outcomes were reduced by MRA therapy overall, with consistent effects across SBP categories (e.g., all-cause mortality, overall hazard ratio [HR] of 0.72; 95% CI: 0.64 to 0.82; p < 0.001; SBP ≤105 mm Hg; HR: 0.72; 95% CI: 0.56 to 0.94; SBP >105 to ≤115 mm Hg; HR: 0.78; 95% CI: 0.60 to 1.02; SBP >115 to ≤125 mm Hg; HR: 0.71; 95% CI: 0.53 to 0.94; SBP >125 to ≤135 mm Hg; HR: 0.79; 95% CI: 0.57 to 1.10; and SBP > 135 mm Hg; HR: 0.67; 95% CI: 0.50 to 0.90; p for interaction = 0.95). Hypotension was infrequent and not more common with MRA therapy than with placebo, overall (4.6% vs. 3.9%; p = 0.25) or in any SBP category. Conclusions: MRA treatment had little effect on SBP in patients with HFrEF, and the clinical benefits were not modified by baseline SBP. MRA treatment infrequently caused hypotension, even when the baseline SBP was low. The treatment discontinuation rates between MRA and placebo therapy were similar. Low SBP is not a reason to withhold MRA therapy in patients with HFrEF.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Ferreira, Mr Joao Pedro and Jackson, Dr Alice and Jhund, Dr Pardeep and Dewan, Dr Pooja and SERENELLI, Dr MATTEO and McMurray, Professor John and Petrie, Professor Mark
Authors: Serenelli, M., Jackson, A., Dewan, P., Jhund, P. S., Petrie, M. C., Rossignol, P., Campo, G., Pitt, B., Zannad, F., Ferreira, J. P., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:JACC: Heart Failure
ISSN (Online):2213-1787
Published Online:08 January 2020
Copyright Holders:Copyright © 2020 American College of Cardiology Foundation
First Published:First published in JACC: Heart Failure 8(8):188-198
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