P3565Risk of atrial fibrillation in heart failure with preserved ejection fraction: results from the treatment of cardiac function with an aldosterone antagonist (TOPCAT) Study

Abstract

Background: Heart failure (HF) is a recognized risk factor for atrial fibrillation (AF). Aldosterone antagonists, such as spironolactone, reduce the risk of AF in patients with HF and a reduced ejection fraction. However, the efficacy of spironolactone on AF suppression in HF with a preserved ejection fraction (HFpEF) remains unclear. Purpose: To assess the efficacy of spironolactone as prevention of new‐onset AF or treatment for paroxysmal AF (pAF) in patients with HFpEF. Methods: All patients (n: 3,425) with HFpEF from the TOPCAT study were included. They were 1:1 randomised to spironolactone or placebo. New‐onset AF and pAF were defined by using the study case forms, which were made available to the investigators by the National Heart, Lung and Blood Institute. Kaplan‐Meier estimates were used to compute cumulative incidence of AF and log‐rank was used for comparisons. Cox proportional hazards models were used to quantify the risk of new‐onset or recurrence of AF, calculated by hazard ratios (HR) with corresponding confidence intervals (CI). Subgroups analysis based on left atrial volume index (LAVI) was performed. Results: At baseline 2,218 patients (64.8%) had no history of AF (spironolactone, n=1,105; placebo, n=1,113). pAF was present in 501 patients (14.6%) at baseline (spironolactone, n=258; placebo, n=243). LAVI was significantly lower in patients without a history of AF (25.9±9.3 versus 30.9±10.8 ml/m2 p<0.001) compared to pAF. During a median follow‐up of 3.1 (IQR 2.0‐4.9) years, new‐onset AF occurred in 5.2% (n: 58) versus 4.3% (n: 48) patients treated with spironolactone or placebo respectively (p=0.35). The risk of new‐onset of AF did not significantly differ between spironolactone and placebo, HR: 0.82 (CI 0.56‐1.21, p=0.32). Also, stratification by LAVI showed a nonsignificant influence on risk of new‐onset AF in patients without a history of AF (LAVI <25.9 ml/m2, HR: 0.75 (CI 0.20‐2.80, p=0.67); LAVI ≥25.9 ml/m2: HR: 1.13 (CI 0.39‐3.21, p=0.83). During a median follow‐up of 3.3 (IQR 1.9‐4.7) years, AF recurred in 11.6% (n: 30) versus 11.9% (n: 29) of patients with pAF treated with spironolactone or placebo respectively (p=1.00). The risk of recurrence of AF was the same between spironolactone and placebo, HR: 1.05 (CI 0.63‐1.76, p=0.84). Similarly, stratification by LAVI showed a nonsignificant influence on risk of recurrence in patients with pAF (LAVI <30.9 ml/m2, HR: 3.04 (CI 0.78‐11.8, p=0.11); LAVI ≥30.9 ml/m2: HR: 1.08 (CI 0.35‐3.37, p=0.89). Conclusion: Spironolactone treatment does not reduce the risk of new‐onset or of recurrence of AF in patients with HFpEF. These data contrast to cohorts of patients with HF and a reduced ejection fraction. (Figure Presented).