Effect of Combined Spironolactone–β-Blocker ± Enalapril Treatment on Occurrence of Symptomatic Atrial Fibrillation Episodes in Patients With a History of Paroxysmal Atrial Fibrillation (SPIR-AF Study)

Angiotensin II and aldosterone are key factors responsible for the structural and neurohormonal remodeling of the atria and ventricles in patients with atrial fibrillation (AF). The aim of the present study was to evaluate the antiarrhythmic effects of spironolactone compared to angiotensin-converting enzyme inhibitors in patients with recurrent AF. A cohort of 164 consecutive patients (mean age 66 years, 87 men), with an average 4-year history of recurrent AF episodes, was enrolled in a prospective, randomized, 12-month trial with 4 treatment arms: group A, spironolactone, enalapril, and a β blocker; group B, spironolactone and a β blocker; group C, enalapril plus a β blocker; and group D, a β blocker alone. The primary end point of the trial was the presence of symptomatic AF episodes documented on the electrocardiogram. At 3-, 6-, 9-, and 12 months, a significant (p <0.001) reduction had occurred in the incidence of AF episodes in both spironolactone-treated groups (group A, spironolactone, enalapril, and a β blocker; and group B, spironolactone plus a β blocker) compared to the incidence in patients treated with enalapril and a β blocker (group C) or a β blocker alone (group D). No significant difference was seen in AF recurrences between patients taking spironolactone and a β blocker with (group A) and without (group B) enalapril. No significant differences were found in the systolic or diastolic blood pressure or heart rate among the groups before and after 1 year of follow-up. In conclusion, combined spironolactone plus β-blocker treatment might be a simple and valuable option in preventing AF episodes in patients with normal left ventricular function and a history of refractory paroxysmal AF.