Rate versus rhythm control in patients with atrial fibrillation: what the trials really say.

Despite new insights into the pathophysiological triggers of atrial fibrillation (AF) and the development of novel ablative techniques and antiarrhythmic drugs, the management of this chronic rhythm disturbance remains problematic. At present, there are two fundamental interventional choices: restoration and maintenance of normal sinus rhythm (NSR) or control of the ventricular rate. While there are compelling theoretical benefits in restoring and maintaining NSR, until recently there has been little evidence supporting the comparative advantages of either strategy. During the past few years, five randomised trials investigating the two treatment strategies have been completed: PIAF (Pharmacological Intervention in Atrial Fibrillation), STAF (Strategies of Treatment of Atrial Fibrillation), RACE (RAte Control versus Electrical conversion), AFFIRM (Atrial Fibrillation Follow-up of Rhythm Management) and HOT-CAFE (How to Treat Chronic Atrial Fibrillation). Results from these studies indicate that a strategy of rate control in AF patients can be at least as effective as efforts to control rhythm with respect to several specific outcomes. These trials have also revealed the necessity of continuing antithrombotic treatment even when long-term sinus rhythm is obtained. However, these trials had different patient selection criteria, endpoints and therapeutic interventions, limiting the applicability of their findings to all AF populations. This article looks beyond the primary results from these important studies, using recent substudy analyses to draw new conclusions and to generate hypotheses that will require prospective evaluation in adequately powered trials. One substudy suggested, for instance, that failure of rhythm control to show superiority may be a result of the toxicity of current antiarrhythmic drugs. New class III compounds with novel mechanisms are now in varying stages of clinical development. These drugs appear to block multiple membrane ion channels, with predominant effects on the atria and low proarrhythmic potential. It is anticipated that these agents will be safer than, and at least as effective as, currently available drugs, thereby reducing AF-related morbidity and mortality. Until more effective treatments are available, physicians should use the evidence generated from the major studies to guide decision making based upon the characteristics and symptomatic presentation of individual patients.