Effect of Spironolactone on Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: Post-Hoc Analysis of the Randomized, Placebo-Controlled TOPCAT Trial

Jolien Neefs, Nicoline W E van den Berg, Sébastien P J Krul, S Matthijs Boekholdt, Joris R de Groot, Jolien Neefs, Nicoline W E van den Berg, Sébastien P J Krul, S Matthijs Boekholdt, Joris R de Groot

Abstract

Background: Mineralocorticoid receptor antagonists (MRAs) reduce the risk of atrial fibrillation (AF) in patients with heart failure (HF) and a reduced ejection fraction. The efficacy of MRAs for AF prevention in patients with HF and a preserved ejection fraction (HFpEF) is unclear.

Objectives: We performed a secondary analysis of a randomized placebo-controlled trial to determine the efficacy of spironolactone in reducing new-onset AF and recurrence of AF in 2733 patients with symptomatic HFpEF.

Methods: Patients with and without prevalent AF at baseline were included, and those with permanent AF were excluded. Patients were randomized 1:1 to spironolactone or placebo. The risk of new-onset AF or the recurrence of AF was quantified using hazard ratios (HRs) with corresponding 95% confidence intervals (CIs).

Results: At baseline, 2228 (64.7%) patients had no history of AF (spironolactone, n = 1111; placebo, n = 1117), whereas 505 (18.4%) patients had prevalent AF (spironolactone, n = 260; placebo, n = 245). During a median follow-up of 3.1 years (interquartile range [IQR] 2.0-4.9), the incidence of new-onset AF was similar in both treatment arms: spironolactone 5.2% (n = 58) versus placebo 4.4% (n = 49); p = 0.41. The risk of new-onset AF was similar in both treatment arms: HR 1.19; 95% CI 0.81-1.74; p = 0.38. AF recurrence was also similar in both treatment arms during a median follow-up of 3.3 years (IQR 1.9-4.7): spironolactone 11.5% (n = 30) versus placebo 11.8% (n = 29); p = 1.00. The risk of recurrence of AF did not differ per treatment arm: HR 0.94; 95% CI 0.57-1.58; p = 0.83.

Conclusion: Spironolactone does not reduce the risk of new-onset AF or AF recurrence in patients with HFpEF. This is in contrast to results in cohorts of patients with HF and a reduced ejection fraction.

Clinical trial registration: ClinicalTrials.gov identifier no. NCT00094302 (TOPCAT).

Conflict of interest statement

Dr. de Groot is a consultant for AtriCure and Daichii Sankyo; has received research grants from AtriCure, Medtronic, Boston Scientific and Abbott and a grant from ZonMW/now (106.146.310) outside the submitted work. Jolien Neefs, Nicoline van den Berg, Sébastien Krul and S. Matthijs Boekholdt have no potential conflicts of interest that might be relevant to this work.

Figures

Fig. 1
Fig. 1
Cumulative hazard ratio (%) of a new-onset atrial fibrillation (AF) and b recurrence of AF for spironolactone versus placebo
Fig. 2
Fig. 2
Number of patients with new-onset AF or recurrence of AF during follow-up for spironolactone versus placebo. AF atrial fibrillation, CI confidence interval, HR hazard ratio
Fig. 3
Fig. 3
Forest plot of the hazard ratios of new-onset AF or recurrence of AF stratified for region of inclusion. The Americas included the USA, Canada, Argentina and Brazil. AF atrial fibrillation, CI confidence interval, HR hazard ratio, p p value

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Source: PubMed

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