One in four men and women above 40 years of age can expect to develop atrial fibrillation (AF) in their lifetime.1， 2The burden of AF on healthcare system is overwhelming， given its independent association with stroke and systemic thromboembolism， heart failure， and mortality.1An old controversy regarding the management of AF is whether restoring and maintaining sinus rhythm (i.e.， rhythm-control therapy) should be preferred to an approach aimed at controlling only the ventricular rate during AF (i.e.， rate-control therapy).3-6 This article will briefly review the state of the art on rhythm- versus rate-control treatment strategies for AF.
Rhythm- versus rate-control: pharmacological trials
There is no question that AFindependently increases the risk of stroke， heart failure， and mortality compared to normal sinus rhythm.1， 2， 7 Accordingly， restoring and maintaining sinus rhythm (coupled with prevention of thromboembolic complications) is the main endpoint of AF treatment. The controversy on rate- versus rhythm-control for AF essentially derives from the fact that “rhythm-control” therapy， at least with currently available antiarrhythmic drugs， does not translate into a consistent restoration and maintenance of sinus rhythm.4The long-term effectiveness of currently available pharmacological agents for the rhythm-control of AF is clearly suboptimal.8In the Canadian Trial of Atrial Fibrillation， sinus rhythm was maintained in only 37% of patients receiving sotalol or propafenone at an average follow-up of 16 months， and in about 65% of those receiving amiodarone.9 Similar findings were confirmed in a pooled analysis of pharmacological trials comparing rhythm-control versus rate-control for AF， with an incremental benefit in terms of AF-free survival for antiarrhythmic drug therapy of only 21.5%， 33.1%， and 17.4% for class IA， IC， and class III agents， respectively.10 Taken together， these findings contributed to the false perception that rhythm-control and rate-control in AF are equivalent strategies.1
On the other hand， when analyzing the data from such large trials according to the patients’ actual rhythm， being consistently in sinus rhythm was confirmed as one of the most powerful predictors of survival.11In a sub-analysis of theAF Follow-up Investigation of Rhythm Management(AFFIRM) trial， patients in sinus rhythm had almost 50% lower mortality as compared to those in AF;11 similar findings have been confirmed in other large multicenter studies.12， 13In addition， use of antiarrhythmic drugs has been alsoreported to be associated with increased mortality， which possibly offsets the survival benefit of sinus rhythm maintenance.14 In conclusions， large pharmacological trials comparing rhythm- versus rate-control for AF mainly prove the inadequacy of current antiarrhythmic pharmacological agents to effectively restore and maintain sinus rhythm. On the other side， if sinus rhythm is effectively restored and consistently maintained， there is no doubt that this would translate in a survival benefit， as presence of AF per se has been independently associated with increased risk of morbidity and mortality in multiple studies.
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