Abstract 16516: Spironolactone In Patients With Atrial Fibrillation And Preserved Ejection Fraction Does Not Reduce Arrhythmia Burden: Results From A Randomized, Double-blind, Placebo-controlled Trial (INSPIRE-AF)

BackgroundSpironolactone has antifibrotic properties and may reduce the burden of arrhythmia in patients with atrial fibrillation (AF). PurposeTo evaluate the efficacy of spironolactone versus placebo added to optimal standard medical treatment in patients with paroxysmal and persistent AF with respect to arrhythmia burden, defined as the total number of documented recurrent episodes of AF.MethodsINSPIRE-AF is an investigator-initiated, randomized, double-blind, placebo-controlled trial NCT02764619). Study participants with paroxysmal (n=58) and persistent (n=67) non-valvular AF, left ventricle ejection fraction (LVEF) ≥40%, with or without hypertension, symptomatic recurrent AF (EHRA score ≥II), and no prior ablation were randomized to either spironolactone 25 mg (SPL group) or placebo (PL group) once daily in addition to guideline-directed care. Recurrent episodes of AF were documented with 12-lead electrocardiograms. The number of direct current (DC) cardioversions were recorded.ResultsA total of 125 subjects (mean age 64 years, 64% male, LVEF 55±6%) were randomized to the SPL-group (n=63) and the PL-group (n=62), respectively. Baseline characteristics, including medication use, were similar between the two groups. Subjects in the SPL-group more often discontinued their study medication due to adverse events (9.5%) than those in the PL-group (3.2%), but mean time on study medication did not differ significantly (SPL-group= 363±64 days vs. PL-group=354±72 days, P=0.47). We found no evidence of reduction in the total arrhythmia burden (IRR=0.79, P=0.17) or in the total number of DC cardioversions (IRR=0.92, P=0.83) with SPL. In addition, there was no significant difference in time-to-first-AF recurrence (HR=0.94, P=0.81), even when stratified for type AF (HR with SPL =0.93, P=0.80). The risk of hyperkalemia (serum-potassium≥5 mmol/L) and gynecomastia were increased in SPL-group (for both P