- PURPOSE OF REVIEW: This review summarizes recent clinical trial evidence showing a reduction in the development and recurrence of atrial fibrillation with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor-blocking agents (ARBs). It then explores the possible mechanisms for this effect based on current animal models and limited human study. RECENT FINDINGS: Post hoc analyses of trials in patients with heart failure, hypertension, or myocardial infarction have observed reductions in atrial fibrillation among patients treated with ACE inhibitors or ARBs. Recent studies of these agents in animal models of atrial fibrillation suggest that they may prevent atrial fibrillation by reversing the cardiac structural and electrical changes, known as cardiac remodeling, that lead to the development of atrial fibrillation. This concept is also supported by two prospective studies showing that ACE inhibitors and ARBs prevent the recurrence of atrial fibrillation after electrical cardioversion. SUMMARY: Inhibition of the renin-angiotensin-aldosterone system is a novel concept for the treatment of atrial fibrillation that may target the underlying substrate of atrial fibrillation. Further human research is required to determine whether ACE inhibitors and ARBs prevent atrial fibrillation, and if so, whether this is a result of blood pressure lowering alone or a specific effect of these agents. Ongoing research will establish whether ACE inhibitors or ARBs have specific benefits in patients with atrial fibrillation.