Author + information
- Received June 20, 2019
- Revision received September 9, 2019
- Accepted September 10, 2019
- Published online January 8, 2020.
- Matteo Serenelli, MDa,b,
- Alice Jackson, MBChBa,
- Pooja Dewan, MBBSa,
- Pardeep S. Jhund, MBChB, PhDa,
- Mark C. Petrie, MBChBa,
- Patrick Rossignol, MD, PhDc,
- Gianluca Campo, MDb,d,
- Bertram Pitt, MDe,
- Faiez Zannad, MD, PhDc,
- João Pedro Ferreira, MD, PhDa,c and
- John J.V. McMurray, MDa,∗ ()
- aBritish Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
- bCardiovascular Centre of Ferrara University, Ferrara University, Ferrara, Italy
- cCentre d'Investigations Cliniques Plurithématique 1433, Université de Lorraine INSERM, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, France
- dGruppo Villa Maria Care & Research, Maria Cecilia Hospital, Cotignola (RA), Italy
- eDepartment of Internal Medicine-Cardiology, University of Michigan School of Medicine, Ann Arbor, Michigan
- ↵∗Address for correspondence:
Prof. John J.V. McMurray, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, United Kingdom.
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 (95% confidence interval [CI]: 1.5 to 3.6; p < 0.001) mm Hg. 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.
- blood pressure
- ejection fraction
- heart failure
- mineralocorticoid receptor
Dr. Ferreira is supported by an European Society of Cardiology research grant for collaboration with the University of Glasgow. Drs. Ferreira, Rossignol, and Zannad are supported by French National Research Agency Fighting Heart Failure grant ANR-15-RHU-0004, by the French PIA project “Lorraine Université d’Excellence” Functional Genomic, Epigenomic and ENvironment interplay to IMPACT the Understanding, diagnosis and management of healthy and pathological AGEing grant ANR-15-IDEX-04-LUE programmes, the Contrat de Plan Etat Région Lorraine, and the FEDER IT2MP. Dr. McMurray is supported by British Heart Foundation Centre of Excellence grant number RE/18/6/34217. Dr. Jhund is a consultant for and has received advisory board and speakers fees from Novartis, Vifor Pharma, Cytokinetics, and Boheringer Ingelheim; and has received research support from Boehringer Ingelheim. Dr. Petrie is a consultant for and has received speakers fees from Boehringer Ingelheim, Servier, Novartis, Maquet, Takeda, Astra, Daiichi Sankyo, Novo Nordisk, SC Pharmaceuticals, Corvia, Pfizer, and Vifor. Dr. Pitt is a consultant for Bayer, AstraZeneca, Sanofi, KBP Biosciences, Sarfez, Relypsa/Vifor, Tricida, and Stealth Peptides; holds stock options in KBP Biosciences, Sarfez, Relypsa/Vifor, and Tricida; and holds U.S. patent 9931412. Dr. Rossignol is a consultant for Novartis, NovoNordisk, Relypsa, AstraZeneca, Grunenthal, Idorsia, Stealth Peptides, Fresenius, and Vifor; has received lecture fees from Bayer and CVRx; and is a cofounder of CardioRenal. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 20, 2019.
- Revision received September 9, 2019.
- Accepted September 10, 2019.
- 2020 American College of Cardiology Foundation
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