Atrial Fibrillation: What Have Recent Trials Taught Us Regarding Pharmacologic Management of Rate and Rhythm Control?

The management of atrial fibrillation (AF) focuses on control of heart rate, correction of rhythm disturbance, prophylaxis of thromboembolism, treatment of underlying disorders, and pathophysiologic mechanisms, and more recently on costs, hospitalizations, and other AF consequences. The goals of therapy are to reduce morbidity and mortality and improve quality of life (QOL). Several large studies have examined the relative efficacy of rhythm- versus rate-control strategies with respect to these outcomes, and have largely failed to demonstrate a survival advantage with either approach by intention-to-treat analysis--both in patients with and without heart failure (HF). However, the results do not support the hypothesis that rate control is preferable as first-line therapy for AF with respect to survival and do not disprove the hypothesis that maintenance of sinus rhythm is preferable to the continuation of AF, particularly if rate control fails to restore adequate QOL or if selective approaches are employed. Many post hoc analyses and substudies have assessed QOL, functional status, and exercise tolerance, with the majority demonstrating important benefits associated with achievement of rhythm control. Moreover, some subanalyses and additional trials have suggested that sinus rhythm can be associated with longer survival, including in patients with HF. In addition, ATHENA demonstrated that a drug, dronedarone, could improve the composite endpoint of cardiovascular hospitalizations and all-cause mortality in a carefully selected, high-risk, nonpermanent AF population, in addition to its recognized reduction in AF. This review examines the clinical outcomes of several important AF trials, discusses the limitations in applying the major morbidity/mortality findings to everyday clinical practice, and summarizes the lessons learned.