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Other than anticoagulation, what is the best therapy for those with atrial fibrillation?


Rate control with long-term anticoagulation is recommended for most patients with atrial fibrillation (strength of recommendation [SOR]: A, based on randomized controlled trials [RCTs]). A rhythm-control strategy provides no survival or quality-of-life benefit when compared with rate control and causes more adverse drug effects and increased hospitalizations (SOR: A, based on RCTs).

Non-dihydropyridine calcium-channel blockers (diltiazem, verapamil) and most beta-blockers are effective for controlling heart rate both at rest and during exercise (SOR: A, based on RCTs). Digoxin is only effective for rate control at rest and should be reserved for patients with systolic dysfunction or as an adjunct for those inadequately rate-controlled on calcium-channel blockers or beta-blockers (SOR: B, based on RCTs).

Subgroups in whom rhythm control may be superior are patients with persistent fatigue and dyspnea despite ventricular rate control and those unable to achieve adequate rate control. Both pharmacologic conversion (SOR: B, based on RCTs) and direct-current cardioversion (SOR: B, based on observational studies) are appropriate options in these patients.

Long-term anticoagulation is necessary for high-risk patients even if they are successfully managed with rhythm control (SOR: A, based on RCTs).


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-to-treat 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], brady-cardia [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)

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 sample 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%.)


The American Academy of Family Practice/ American College of Physicians' clinical guidelines support a rate-control strategy for most patients with atrial fibrillation and recommend atenolol, metoprolol, diltiazem, or verapamil as the first-choice drugs. (8) Digoxin is recommended as a second-line agent. DC cardioversion and pharmacologic conversion for patients who desire a rhythm-control strategy are described as "appropriate options." (8)


(1.) Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347:1825-1833.

(2.) Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation--Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet 2000; 356:1789-1794.

(3.) Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002; 347:1834-1840.

(4.) Carlsson J, Miketic S, Windeler J, et al. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the strategies of treatment of atrial fibrillation (STAF) study. J Am Coll Cardiol 2003; 41:1690-1696.

(5.) Opolski G, Torbicki A, Kosior D, et al. Rhythm control versus rate control in patients with persistent atrial fibrillation. Results of the HOT CAFE Polish study. Kardiol Pol 2003; 59:1-16.

(6.) McNamara RL, Tamariz LJ, Segal JB, Bass EB. Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography. Ann Intern Med 2003; 139:1018-1033.

(7.) Segal JB, McNamara RL, Miller MR, et al. The evidence regarding the drugs used for ventricular rate control. J Fam Prac 2000;49:47-59.

(8.) Snow V, Weiss KB, LeFevre M, et al. Management of newly detected atrial fibrillation: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Intern Med 2003; 139:1009-1017.

(9.) AFFIRM First Antiarrhythmic Drug Substudy Investigators. Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug. J Am Coll Cardiol 2003; 42:20-29.


Rate control best for atrial fibrillation

AFFIRMed at last, it's rate-controlling and not rhythm-controlling drugs that get the evidence-based nod for most types of atrial fibrillation. While rate and rhythm control were equally efficacious in most patient-oriented outcomes, the antiarrhythmics sent more people to the hospital and, potentially, killed more people than the rate controlling medications. The antiarrhythmics, especially amiodarone, (9) do have a place in maintaining sinus rhythm in select patients with atrial fibrillation; but that role is limited and may be best managed with the help and support of a cardiologist.

The atrial fibrillation evidence also suggests that we need to place beta-blocker and non-dihydropyridine calcium-channel blockers (ie, verapamil and diltiazem) as first-line choices for rate-control therapy. Digoxin still has a place in our medical armamentarium; but its role is as an adjunct or backup to the blockers for most patients.

Clint Koenig, MD, MS, Fulton, Missouri

Kara Cadwallader, MD, Family Practice Residency of Idaho, University of Washington, Seattle; Terry Ann Jankowski, MLS, University of Washington Health Sciences Libraries, Seattle
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Title Annotation:Clinical inquiries: from the family practice inquiries network
Author:Cadwallader, Kara; Jankouski, Terry Ann
Publication:Journal of Family Practice
Geographic Code:1USA
Date:Jul 1, 2004
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