Drug Therapy in Atrial Fibrillation Management: Where Do We Stand in 2010? of the AF rhythm.12 AF Management Although AF is a benign disease, it is associated with increased morbidity. Of great significance are heart failure and stroke.13 Indeed, the risk of stroke significantly increases in AF (23.3% life-time risk in patients between 80 and 89 years of age).14 AF management creates a high economic burden because of the concomitant presence of heart failure, coronary artery disease, hypertension, and the need for frequent hospitalizations. Expensive antiarrhythmic drugs and interventional procedures are other important factors that raise the costs of AF care.15 Four major aspects should be considered in the AF management: I- Symptom control by slowing ventricular response during paroxysmal or persistent AF and long-term rate control in permanent AF, II- Cardioversion to sinus rhythm, III- Maintenance of sinus rhythm after successful cardioversion, and IV- Prevention of complications and thromboembolic events.15 The first three objects are related but anticoagulation is a different aspect in the AF management.16 In cases where there is a treatable cause for AF (endocrine disease, inflammation, cardiac surgery, etc.), there may be no need for the long-term management of AF except when treating the underling condition.16 Monotherapy with digoxin maybe a good option for old patients and ventricular rate response is an acceptable index for the evaluation of response to therapy.17 Be that as it may, digoxin is not an ideal drug for this purpose because it works well in lowering ventricular response at rest but with less effect during exertion. Adding a beta blocker or calcium antagonist may be useful, but in older patients it should be done cautiously.17 Rhythm versus Rate Control In order to prevent the complications and symptoms of AF, two main strategies exist: I - Rhythm control: converting the patient’s rhythm to sinus and maintaining the sinus rhythm, and II - Rate control: slowing the ventricular response rate without insisting on conversion to sinus rhythm.18 From a theoretical point of view, converting AF into sinus rhythm is the best option.6 Nonetheless; the most important trials reported in the existing literature thus far have mentioned no significant difference in terms of quality of life and other outcomes between the two strategies. It seems that the side effects of antiarrhythmic agents (pro-arrhythmia) in the long term, poor efficacy of drugs in the maintenance of sinus rhythm, and inappropriate discontinuation of anticoagulants TEHRAN HEART CENTER in the patients who still have AF episodes can interfere with good results in the rhythm-control arm.16 Therefore, many experts believe that rhythm control with safe antiarrhythmic drugs or catheter ablation will play an important role in the AF management. Antiarrhythmic agents from class IA, IC, and III can be effective; and by using less toxic drugs, the risk of tachycardia- mediated cardiomyopathy can also be lowered.19, 20 The main agents for slowing ventricular response in AF are beta blockers, calcium channel blockers, and digoxin.17 In the AFFIRM study, there was no survival difference between rate-control and rhythm-control strategies. In addition, the lower risk of adverse drug effects in the rate-control arm conferred some advantages in this arm. A post-hoc analysis of the AFFIRM data proved that there was no significant benefit in the rhythm-control group versus the rate-control group in patients with AF and left ventricular dysfunction.21 The RACE study showed that for the prevention of cardiovascular mortality and morbidity in AF, rhythm control was not superior to rate control.22 A later analysis of the RACE data showed that the rhythm-control strategy in AF patients with hypertension was associated with increased cardiovascular morbidity and mortality; accordingly, the rate-control strategy was deemed superior.23 In the PIAF trial, clinical outcomes were similar between the rate-control group and the rhythm-control group but exercise tolerance was better in the rhythm-control arm.24 The STAF study showed no difference between the two main strategies of the AF management in all end-points except for hospitalization.25 The HOT CAFÉ study demonstrated that rate control was similar to rhythm control with respect to AF mortality and morbidity such as stroke, thromboembolic events, and bleeding.26 Guedon-Moreau et al. posited that the management of paroxysmal AF with flecainide was associated with improved quality of life.27 Serial cardioversion in heart failure patients is correlated with poor outcome compared with normal left ventricular ejection fraction patients.28 The rhythm-control strategy is more popular than the rate-control strategy worldwide. Still, it seems that in patients with recurrent AF after cardioversion, slowing the ventricular response may be the choice and first step. Those with long-standing AF or previous failure of antiarrhythmic drugs should be selected for the rate-control strategy.29 Antiarrhythmic Drugs Class III antiarrhythmic agents have an important role as a part of cardioversion strategy and maintaining sinus rhythm. Amiodarone, which is the hallmark drug in this group, is a relatively safe and effective drug but frequent adverse effects The Journal of Tehran University Heart Center173