PracticeUpdate: Cardiology - Winter 2018

EDITOR’S PICKS 8

Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The TOPCAT Trial JACC: Heart Failure Take-home message • In this study, researchers looked at the association between atrial fibrillation (AF) and outcomes of patients enrolled in the TOPCAT trial. The goal was to determine if AF modified the response to spironolactone and if spironolactone was associated with the incidence of AF in those patients without baseline AF. In the 760 patients with HFpEF studied, spironolactone treatment was not associated with the primary composite outcome of cardiovascular mortality, aborted cardiac arrest, and heart failure hospitalization. Also, spironolactone treatment did not increase the risk of AF in HFpEF patients without baseline AF. • The results indicate that AF increases overall cardiovascular risk in patients with HFpEF, and that spironolactone treatment does not increase or reduce this risk.

COMMENT By Jonathan P. Piccini MD, MHS, FACC, FAHA, FHRS T his analysis from the TOPCAT investigators emphasizes how common atrial fibrillation (AF) is in patients with heart failure and preserved ejection fraction (HFpEF). Overall, 43% of the patients with HFpEF in TOPCAT had AF at the begin- ning of the trial and an additional 6% developed new-onset AF after the beginning of the study. Thus, about half of the HFpEF patients had AF. Patients with AF had higher adjusted rates of the composite outcome of cardiovascular mortality, aborted cardiac arrest, or heart failure. Unfortunately, the occurrence of new-onset AF was not reduced by spironolactone treatment, but the presence of AF did not impact the beneficial treatment effect of spironolactone on reducing the composite outcome of cardiovascular mortality, aborted cardiac arrest, or heart failure. Thus, this important study from TOPCAT highlights that AF is very common and is associated with worse outcomes in HFpEF. Although hyperaldosteronism is associated with an increased risk of AF, 1 the evidence for prevention of AF with mineralocorti- coid receptor antagonists has been mixed and these data from TOPCAT continue that trend. 2,3 More work will be required to figure out if spironolactone can effectively prevent primary and recurrent AF in patients with and without heart failure. References 1. Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Incidence of atrial fibrillation and mineralocorticoid receptor activity in patients with medically and surgically treated primary aldosteronism. JAMA Cardiol 2018 Jul 18. doi: 10.1001/jamacardio.2018.2003. [Epub ahead of print] 2. Dabrowski R, Borowiec A, Smolis-Bak E, et al. Effect of combined spironolactone-beta-blocker +/- enalapril treatment on occurrence of symptomatic atrial fibrillation episodes in patients with a history of paroxysmal atrial fibrillation (SPIR-AF study). Am J Cardiol 2010;106(11):1609-1614. 3. Pretorius M, Murray KT, Yu C, et al. Angiotensin-converting enzyme inhibition or mineralocorticoid receptor blockade do not affect prevalence of atrial fibrillation in patients undergoing cardiac surgery. Crit Care Med 2012;40(10):2805-2812.

Abstract OBJECTIVES This study assessed the relationship between atrial fibrilla- tion (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evalu- ate 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 frac- tion (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 enroll- ment. 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 Seven hundred sixty 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 ben- eficial treatment effect of spironolactone. Post-randomization AF, which occurred in 6.3% of patients, was not influenced by spironolactone treat- ment, 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 cardiovas- cular 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. Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The TOPCAT Trial. JACC Heart Fail 2018 Jul 06;[EPub Ahead of Print], M Cikes, B Claggett, AM Shah, et al. www.practiceupdate.com/c/70960

Dr. Paccini is a Clinical Cardiac Electrophysiologist and Associate Professor of Medicine at Duke University Medical Center and the Duke Clinical Research Institute in Durham, North Carolina.

PRACTICEUPDATE CARDIOLOGY