Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The TOPCAT Trial

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)