Impact of eplerenone on major cardiovascular outcomes in patients with systolic heart failure according to baseline heart rate
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Increased resting heart rate is a risk factor for cardiovascular mortality and morbidity. Mineralocorticoid receptor antagonists (MRAs) have been shown to improve cardiac sympathetic nerve activity, reduce heart rate and attenuate left ventricular remodelling. Whether or not the beneficial effects of MRA are affected by heart rate in heart failure patients with reduced ejection fraction (HFREF) is unclear.
We undertook a secondary analysis of data from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure study to assess if clinical outcomes, as well as the efficacy of eplerenone, varied according to heart rate at baseline.
High resting heart rate of 80 bpm and above predisposed patients to greater risk of all outcomes in the trial, regardless of treatment allocation. The beneficial effects of eplerenone were observed across all categories of heart rate. Eplerenone reduced the risk of primary endpoint, the composite of cardiovascular death and hospitalisation for heart failure, by 30% (aHR 0.70; 95% CI 0.54–0.91) in subjects with heart rate ≥ 80 bpm, and by 48% (aHR 0.52; 95% CI 0.33–0.81) in subjects with heart rate ≤ 60 bpm. Eplerenone also reduced the risks of hospitalisation for heart failure, cardiovascular deaths and all-cause deaths independently of baseline heart rate.
Baseline heart rate appears to be an important predictor of major clinical outcome events in patients with HFREF, as has been previously reported. The benefits of eplerenone were preserved across all categories of baseline heart rate, without observed heterogeneity in the responses.
KeywordsClinicalTrials.gov identifier: NCT00232180 Heart rate Aldosterone antagonists Aldosterone Heart failure
The late Professor Henry Krum made substantial contributions to the study.
The EMPHASIS-HF Study was sponsored by Pfizer.
Compliance with ethical standards
Conflict of interest
Drs Pitt, McMurray, Swedberg, van Veldhuisen, Pocock, and Zannad were members of the EMPHASIS-HF Writing Committee and report having received fees and travel support in the past from the study sponsor, Pfizer Inc, for participation in and traveling to meetings of the committee. Dr Vincent is currently employed by Pfizer and owns stock in Pfizer Inc, the makers of eplerenone. Dr Pitt reports receiving fees for serving on the board of Novartis, consulting fees from Takeda, AstraZeneca, Boehringer Ingelheim, GE Healthcare, Relypsa, BG Medicine, Nile Therapeutics, Merck, Forest Laboratories, and Novartis, grant support from Forest Laboratories and Novartis, and stock options from Relypsa, BG Medicine, Nile Therapeutics, and Aurasenc and that his institution receives grant support from Forest Laboratories on his behalf and he and his institution receive grant support from Bayer. Dr Swedberg has received research support from Pfizer, Amgen, Novartis, and Servier. Dr Pocock reports receiving consulting fees from Servier, Amgen, AstraZeneca, and Novartis and that his institution receives grants from Servier and AstraZeneca on his behalf. Dr Zannad reports receiving fees for serving on the board of Boston Scientific, consulting fees from Novartis, Takeda, AstraZeneca, Boehringer Ingelheim, GE Healthcare, Relypsa, Servier, Boston Scientific, Bayer, Johnson & Johnson, and Resmed, and speaker’s fees from Pfizer and AstraZeneca and that his institution receives grant support from BG Medicine and Roche Diagnostics on his behalf. Dr Liew reports receiving grants and honoraria from Abbvie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Pfizer, Sanofi and Shire. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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