Beta-Blockers Versus Flecainide for Atrial Fibrillation: A First-Line Strategy Review of Efficacy, Safety, and Patient Selection

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The choice of initial pharmacotherapy-rate control versus rhythm control and which agent-is a critical clinical decision. Beta‑blockers and flecainide are both used first line, but have distinct mechanisms and safety profiles that dictate appropriate patient selection. This state‑of‑the‑art review provides a clinically focused, evidence‑based comparison of beta‑blockers and flecainide for first‑line AF management, emphasizing patient selection and practical decision‑making, synthesizing data from landmark trials (Cardiac Arrhythmia Suppression Trial, Atrial Fibrillation Follow-up Investigation of Rhythm Management, RACE, EAST‑AFNET 4), recent guidelines (American College of Cardiology/American Heart Association/American College of Chest Physicians/Heart Rhythm Society 2023, European Society of Cardiology 2020), and contemporary studies. Beta‑blockers are safe and mortality‑reducing in patients with structural heart disease (coronary artery disease, heart failure with reduced ejection fraction, left ventricular hypertrophy) and are effective for both rate and rhythm control. Flecainide offers superior rhythm control efficacy but is absolutely contraindicated in structural heart disease due to proarrhythmic risk (Cardiac Arrhythmia Suppression Trial). In patients with structurally normal hearts, flecainide is a first‑line rhythm‑control option, including a "pill‑in‑the‑pocket" strategy. No direct head‑to‑head trial compares beta‑blockers versus flecainide as monotherapy. The presence or absence of structural heart disease is the primary determinant of first‑line drug selection. A practical clinical algorithm based on this assessment is provided to guide therapy. Ongoing uncertainties include the role of these agents in the era of early ablation and in heart failure with preserved ejection fraction.