Author + information
- Received February 28, 2018
- Revision received April 30, 2018
- Accepted May 2, 2018
- Published online July 30, 2018.
- Maja Cikes, MD, PhDa,
- Brian Claggett, PhDb,
- Amil M. Shah, MD, MPHb,
- Akshay S. Desai, MD, MPHb,
- Eldrin F. Lewis, MD, MPHb,
- Sanjiv J. Shah, MDc,
- Inder S. Anand, MD, PhDd,
- Eileen O’Meara, MDe,
- Jean L. Rouleau, MDe,
- Nancy K. Sweitzer, MD, PhDf,
- James C. Fang, MDg,
- Sanjeev Saksena, MDh,
- Bertram Pitt, MDi,
- Marc A. Pfeffer, MD, PhDb and
- Scott D. Solomon, MDb,∗ ()
- aDepartment of Cardiovascular Diseases, University of Zagreb School of Medicine, Zagreb, Croatia
- bBrigham and Women's Hospital, Boston, Massachusetts
- cNorthwestern University Feinberg School of Medicine, Chicago, Illinois
- dVA Medical Center, Minneapolis, Minnesota
- eMontreal Heart Institute and Université de Montreal, Montreal, Quebec, Canada
- fSarver Heart Center, Division of Cardiovascular Medicine, University of Arizona, Tucson, Arizona
- gUniversity of Utah School of Medicine, Salt Lake City, Utah
- hRutgers-Robert Wood Johnson Medical School, Piscataway, New Jersey
- iUniversity of Michigan School of Medicine, Ann Arbor, Michigan
- ↵∗Address for correspondence:
Dr. Scott D. Solomon, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115.
Objectives This study assessed the relationship between atrial fibrillation (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-randomization AF.
Background AF is common in heart failure with preserved ejection fraction (HFpEF) and likely contributes to increased risk of adverse outcomes.
Methods A total 1,765 patients enrolled in TOPCAT trial in North and South America were divided into 3 groups: no known AF, history of AF without AF at enrollment, and AF found on the electrocardiogram (ECG) at enrollment. We assessed outcomes and treatment response to spironolactone in all groups, and the association between post-randomization AF and outcomes in patients free of AF at baseline. The primary outcome of the TOPCAT trial was a composite of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization.
Results A total of 760 patients (43%) had a history of AF (18%) or AF on ECG at enrollment (25%). The highest adjusted risk was associated with AF at enrollment (primary outcome, hazard ratio: 1.34; 95% confidence interval: 1.09 to 1.65; p = 0.006; and an increased early risk of secondary outcomes). Neither history of AF nor AF at enrollment modified the beneficial treatment effect of spironolactone. Post-randomization AF, which occurred in 6.3% of patients, was not influenced by spironolactone treatment, but was associated with an increased early risk of the primary outcome (hazard ratio: 2.32; 95% confidence interval: 1.59 to 3.40; p < 0.0001) and secondary outcomes.
Conclusions AF at enrollment was associated with increased cardiovascular risk in HFpEF patients in the TOPCAT study. Post-randomization AF, which was associated with an increased risk of morbidity and mortality, was not influenced by spironolactone. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302)
- atrial fibrillation
- heart failure outcomes
- heart failure with preserved ejection fraction
The TOPCAT study was sponsored by the National Heart, Lung, and Blood Institute (NHLBI). Dr. A.M. Shah was supported by NHLBI grants K08HL116792 and R01HL135008; has received research support from Novartis; and has been a consultant for Philips Ultrasound and Bellerphon. Dr. Desai has received research grants from Novartis; and has been a consultant for Novartis, Abbott, AstraZeneca, Relypsa, DalCor Pharma, Amgen, Boston Scientific, and Boehringer Ingelheim. Dr. Rouleau has been a consultant for Novartis and AstraZeneca. Dr. Sweitzer has received research grants from Novartis and Merck. Dr. Pitt has been a consultant for Bayer, AstraZeneca, Sanofi, KBP Pharmaceuticals, and Relypsa/Vifor; has stock options in KBP Pharmaceuticals, Sarfez, and Relypsa/Vifor; and holds a US Patent (9931412). Dr. Pfeffer has received research grant support from Novartis; has been a consultant for AstraZeneca, DalCor, GlaxoSmithKline, Novartis, Novo Nordisk, Pfizer, Roche, and Sanofi; and has stock options in DalCor. Dr. Solomon has received grants from Alnylam, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Ionis, MyoKardia, NIH/NHLBI, Novartis, Sanofi Pasteur, and Theracos; and has been a consultant for Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Corvia, GlaxoSmithKline, Ironwood, Merck, Novartis, Pfizer, Takeda, and Theracos. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 28, 2018.
- Revision received April 30, 2018.
- Accepted May 2, 2018.
- 2018 American College of Cardiology Foundation