Orally Inhaled Flecainide for Paroxysmal Atrial Fibrillation: Emerging Evidence and Therapeutic Potential in Cardioversion to Sinus Rhythm

Atrial fibrillation (AF) remains the most common sustained arrhythmia, with a growing need for rapid, effective, and patient-centered rhythm control strategies. Inhaled flecainide, a novel formulation of a well-established class individual consideration antiarrhythmic, offers an innovative approach by utilizing the pulmonary route to achieve rapid systemic absorption and therapeutic onset. This review examines the clinical efficacy, safety, and practical implications of inhaled flecainide for the treatment of recent-onset paroxysmal AF. Data from the RESTORE-1 trial and related studies suggest that inhaled flecainide enables conversion to sinus rhythm within 30 minutes at reduced dosages, with fewer systemic side effects compared to intravenous therapies. The most commonly reported adverse events-cough and oropharyngeal discomfort-were transient and nonserious. Despite promising early results, challenges such as delivery device variability, long-term pulmonary safety, and regulatory hurdles remain. Advances in nebulizer technology and drug formulation, including 2-hydroxypropyl-beta-cyclodextrin complexes, aim to improve dosing consistency and therapeutic outcomes. Larger, controlled trials are needed to confirm efficacy, define optimal dosing, and support broader clinical adoption. Inhaled flecainide holds strong potential for use in both clinical and outpatient settings, offering a faster, safer, and more accessible alternative for rhythm control in AF.