Five recent RCTs have demonstrated similar mortality and cardiovascular morbidity in atrial fibrillation patients treated with either a rate-control or rhythm-control strategy. ^1-5

The AFFIRM trial, the largest (n=4060), was a nonblinded, randomized, multicenter study with an average follow-up of 3.5 years.¹ The patients were aged 65 years or older and had at least 1 other risk factor for stroke. The rhythm-control group was given an antiarrhythmic medication chosen by the treating physician, while the rate-control group was given either a beta-blocker, a calcium-channel blocker, digoxin, or a combination of these as needed. Heart-rate goals were a resting pulse under 80 beats per minute, and a pulse after a 6-minute walk under 110 beats per minute. An intention-totreat analysis was followed.

There was no difference between the 2 groups for the composite endpoints of death, disabling stroke, disabling anoxic encephalopathy, major bleeding, or cardiac arrest. A nonsignificant trend was observed for mortality favoring the rate-control group (relative risk [RR]=1.15; 95% confidence interval [CI], 0.99–1.34). Quality-of-life measures were equivalent in the 2 groups at all points in the study.¹

More patients in the rhythm-control group required hospitalization (number needed to harm [NNH]=12.3; P<.001) and had adverse drug effects (P.001 for each of pulmonary events [NNH=18], gastrointestinal events [NNH=17], bradycardia [NNH=56], and prolonged QT [NNH=63]). This trial did not include younger patients without stroke risk factors, or those with paroxysmal atrial fibrillation.¹

The 4 other RCTs also found no greater benefit with a rhythm-control strategy vs rate-control for most patients with atrial fibrillation.^2-5

Two systematic reviews have looked at the efficacy of medications for ventricular rate control in atrial fibrillation.^6,7 The first analyzed 54 trials involving 17 agents and focused on digoxin calcium-channel blockers and beta-blockers. The second systematic review evaluated 45 trials with similar agents. Both reviews were unable to perform mathematical pooling due to the heterogeneity of the studies. However, both showed strong evidence for superior ventricular rate control at both exercise and rest with verapamil and diltiazem compared with placebo.^6,7

All beta-blockers tested were effective in rate-control during exercise and most (excluding labetalol and celiprolol) were effective at rest.^6,7 Digoxin was ineffective during exercise and less effective than beta-blockers or calcium-channel blockers at rest.^6-8 The combination of digoxin plus a calcium-channel blocker or beta-blocker may have increased benefit compared with either drug alone. ⁶ Evidence was insufficient to recommend propafenone, clonidine, or amiodarone for rate control.⁷

In select patients, a rhythm-control approach may be desirable. A meta-analysis of 60 RCTs evaluated 8 drugs for acute cardioversion. Ibutilide, flecainide, dofetilide, propafenone, and amiodarone were found to have the strongest evidence of efficacy.⁶ There was moderate evidence for quinidine and insufficient evidence for disopyramide and sotalol.⁶ Studies of pharmacologic conversion suffer from small ample size, short follow-up, and variable duration of atrial fibrillation.⁶ A review of limited research reveals an 80% to 85% immediate success rate for DC cardioversion, with rare side-effects of ventricular tachycardia, transient AV node dysfunction, and significant skin blistering.⁶

For patients who elect a rhythm-control approach, RCTs demonstrate the need for continued long-term anticoagulation in high-risk patients even if they are maintained in sinus rhythm.^1,4,5 (High-risk patients are defined as those aged >65 years, or those <65 years with 1 or more stroke risk factors: diabetes, hypertension, heart failure, prior transient ischemic attack or stroke or systemic embolism, or echocardiographic evidence of a left atrium >50 mm, a shortening fraction <25%, or an ejection fraction <40%.)