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Objectives: The aim of the present study was to verify whether angiotensin-II converting enzyme (ACE) inhibition is also effective in preventing relapses of lone atrial fibrillation (LAF), that is, in the absence of hypertension and/or heart disease., Background: Several studies have shown that ACE inhibitors are effective in preventing atrial fibrillation (AF) relapses in patients with arterial hypertension or several forms of heart disease, that is, in the presence of clinical conditions that are recognized as causing a higher risk of atrial arrhythmias., Methods: Sixty-two patients admitted to the emergency department of our institution for a first-ever episode of LAF were enrolled in the study after excluding the presence of cardiac or extracardiac conditions known to be associated with an increased risk of AF, by medical history, physical examination, complete echocardiographic study, and the evaluation of blood pressure, thyroid function, urinary catecholamines, serum electrolytes, blood glucose, red blood cell count, and arterial blood gases. After cardioversion to sinus rhythm by intravenous propafenone, patients were randomized to either ramipril 5 mg/day (n = 31) or placebo (n = 31). Holter monitoring and clinical examination were performed every 3 months., Results: After a 3-year follow-up, AF relapses were observed in 3 patients treated with ramipril and in 10 patients allocated to placebo (p < 0.03, Kaplan-Meier, log-rank test). During follow-up, none of the patients developed arterial hypertension or other cardiac or extracardiac condition known to be associated with increased risk of AF, that is, in all patients the diagnosis of LAF was confirmed., Conclusions: Ramipril is effective in preventing relapses of LAF.