Author + information
- Received September 14, 2011
- Revision received November 22, 2011
- Accepted November 29, 2011
- Published online May 1, 2012.
- Karl Swedberg, MD, PhD⁎,⁎ (, )
- Faiez Zannad, MD, PhD†,
- John J.V. McMurray, MD‡,
- Henry Krum, MB, PhD§,
- Dirk J. van Veldhuisen, MD, PhD∥,
- Harry Shi, MS¶,
- John Vincent, MB, PhD¶,
- Bertram Pitt, MD#,
- EMPHASIS-HF Study Investigators
- ↵⁎Reprint requests and correspondence:
Dr. Karl Swedberg, Department of Medicine, Sahlgrenska University Hospital/Östra, 41685 Göteborg, Sweden
Objectives The purpose of this study was to analyze the incidence of new atrial fibrillation or flutter (AFF) in the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) database.
Background Aldosterone antagonism in heart failure might influence atrial fibrosis and remodeling and, therefore, risk of developing AFF. The development of new AFF was a pre-specified secondary endpoint in the EMPHASIS-HF study.
Methods Patients in New York Heart Association functional class II and with ejection fraction ≤35% were eligible for EMPHASIS-HF. History of AFF at baseline was reported by investigators using the study case report form. New onset AFF (in those with no history of AFF at baseline) was reported using a specific endpoint form; in a sensitivity analysis we also examined the effect of eplerenone on AFF reported as an adverse event.
Results New onset AFF was significantly reduced by eplerenone: 25 of 911 (2.7%) versus 40 of 883 (4.5%) in the placebo group (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.35 to 0.96; p = 0.034). The reduction in the primary endpoint with eplerenone was similar among patients with and without AFF at baseline (HR: 0.60, 95% CI: 0.46 to 0.79 vs. HR: 0.70, 95% CI: 0.57 to 0.85, respectively; p for interaction = 0.41). The risk of cardiovascular (CV) death or hospital admission for worsening heart failure, the primary endpoint, was not significantly different in subjects with and without AFF at baseline (both study groups combined: HR: 1.23, 95% CI: 0.81 to 1.86; p = 0.33).
Conclusions In patients with systolic heart failure and mild symptoms, eplerenone reduced the incidence of new onset AFF. The effects of eplerenone on the reduction of major CV events were similar in patients with and without AFF at baseline.
Dr. Swedberg has received research support from Pfizer, Amgen, Novartis, and Servier. Drs. Zannad, McMurray, Krum, van Veldhuisen, Swedberg, and Pitt are members of the EMPHASIS-HF Writing Committee and report receiving support from the study sponsor, Pfizer Inc., for participation in and traveling to meetings of the committee. Mr. Shi and Dr. Vincent are currently employed by Pfizer and own stock in Pfizer Inc., the makers of eplerenone. Dr. McMurray is supported by the Eugene Braunwald Endowment for the Advancement of Cardiovascular Discovery and Care. Dr. van Veldhuisen has board membership fees with Amgen, Alere, Vifor, and Pfizer. The sponsor was responsible for data management and final data analyses. The Writing Committee had full access to all data, and was responsible for the interpretation of the results, the development and writing of the manuscript, and the decision to submit for publication. Members of the medical and scientific departments of the sponsor, Pfizer, supported the work of the Writing Committee, but did not make any scientific or research decisions independent of this committee.
- Received September 14, 2011.
- Revision received November 22, 2011.
- Accepted November 29, 2011.
- American College of Cardiology Foundation