Treatment of Patients with Atrial Fibrillation

DECEMBER 01, 2004
Mohammad J. Tafreshi, PharmD, BCPS; Kim N. Hoang, PharmD; and Melinda L. Adkins, PharmD

Atrial fibrillation (AF) is the most common type of arrhythmia in adults. The incidence of AF is <1% in those under the age of 60 and >8% in those over 80.1

Two recently published articles described current recommendations for the management of patients with AF.1,2 Whereas one is a review that focuses on AF in general, the other article describes the guidelines for newly detected AF.

The present article gives a summary of these recommendations. Following a brief discussion of each topic, we have italicized the recommendations from the guidelines. These comments are taken directly from the American Academy of Family Physicians (AAFP) and the American College of Physicians (ACP) guidelines for management of patients with newly detected AF.

These recommendations do not apply to patients with postoperative or post-myocardial infarction AF, patients with class IV heart failure, patients already taking antiarrhythmic drugs, or patients with valvular disease.1 The Table3 describes the recommendation gradings.


It is imperative for pharmacists, as it is for all other health care professionals, to know the most current recommendations, to practice evidence-based medicine, and to understand the rationale behind the development of specific recommendations in clinical practice guidelines.

Rhythm Control Versus Rate Control

The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) clinical trial had the greatest influence on the recommendations of the AAFP/ACP. The AFFIRM study was a multicenter randomized controlled trial that enrolled 4060 patients. It was the largest study reviewed by the AAFP/ACP.2 In the AFFIRM trial, patients were randomly assigned to receive rate-control or rhythm-control therapy.

Overall mortality was not statistically significantly different between the groups. There was a higher risk for death, however, in the rhythm-control group than in the rate-control group for elderly patients (>65), those without congestive heart failure (CHF), and those with coronary heart disease. Rates of stroke did not differ between groups, but more hospitalizations were reported in the rhythm-control group.4

Other studies that were reviewed by the AAFP/ACP included the RAte Control versus Electrical cardioversion for persistent atrial fibrillation (RACE), the Pharmacological Intervention in Atrial Fibrillation (PIAF), and the Strategies of Treatment of Atrial Fibrillation (STAF) trial. The researchers concluded that none of these trials demonstrated improvement in mortality by aggressively controlling rhythm and that rate control with antithrombotic therapy is as effective as rhythm control in many if not most patients with AF.2

Rate control with chronic anticoagulation is the recommended strategy for the majority of patients with atrial fibrillation. Rhythm control has not been shown to be superior to rate control (with chronic anticoagulation) in reducing morbidity and mortality and may be inferior in some patient subgroups to rate control. Rhythm control is appropriate when based on other special considerations, such as patient symptoms, exercise tolerance, and patient preference.1 (Grading recommendation: 2A)


Sixteen studies were evaluated to determine the role of anticoagulation in patients with AF. According to the AAFP/ACP recommendations, "evidence did not support the use of low-dose warfarin over other treatments,"including conventional-dose warfarin.2 There is strong evidence for the use of warfarin in AF patients who have an average or greater risk for stroke, unless they have an increased risk for bleeding.2 Evidence also may support the use of aspirin in warfarin-ineligible patients who have a lower risk for stroke to manage AF, depending on patients'risks for bleeding.

Patients with atrial fibrillation should receive chronic anticoagulation with adjusted-dose warfarin, unless they are at low risk of stroke or have a specific contraindication to the use of warfarin (thrombocytopenia, recent trauma or surgery, alcoholism).1 (Grading recommendation: 1A)

Rate Control

In the study of chronic AF, the researchers focused on studies evaluating digoxin, calcium-channel blockers (CCBs), and beta-blockers (BBs). Digoxin yielded inconsistent results in rate-control studies. When compared with placebo or digoxin in patients with AF, nondihydropyridine CCBs (verapamil and diltiazem) were effective in reducing ventricular rate both at rest and during exercise. The efficacy of BBs in rate control was "agent specific." Atenolol, metoprolol, timolol, pindolol, and nadolol were shown to control ventricular rate both at rest and with exercise. Both CCBs and BBs showed improved efficacy, compared with digoxin. Some evidence suggests that the addition of digoxin to a BB or nondihydropyridine CCB may provide additional benefit over either drug alone.2

Studies of new-onset AF showed that atenolol and metoprolol improved both resting and exercise rate control, whereas other BBs were less consistent. The combination of digoxin with diltiazem, atenolol, or betaxolol also was effective both at rest and during exercise. Most of these trials excluded patients with CHF.

For patients with atrial fibrillation, the following drugs are recommended for their demonstrated efficacy in rate control during exercise and while at rest: atenolol, metoprolol, diltiazem, and verapamil (drugs listed alphabetically by class). Digoxin is only effective for rate control at rest and therefore should only be used as a second-line agent for rate control in atrial fibrillation.1 (Grading recommendation: 1B)

Acute Conversion

Direct-current cardioversion of AF has become less invasive and more efficient with the advent of external biphasic defibrillators. The immediate efficacy of this method is > 90%. The risk for thromboembolic events does not seem to differ from pharmacologic conversion. Although initiating antiarrhythmic therapy raises concern for the risk of developing torsades de pointes due to QT prolongation, side effects of direct-current cardioversion may include skin burns.1,2 Data do not support the routine use of antiarrhythmic agents before direct-current cardioversion to improve the efficacy of restoring sinus rhythm.2

For those patients who elect to undergo acute cardioversion to achieve sinus rhythm in atrial fibrillation, both direct-current cardioversion (Grading recommendation: 1C+) and pharmacological conversion (Grading recommendation: 2A) are appropriate options.1

Maintenance Therapy

Antiarrhythmic therapy may result in serious ventricular tachycardia such as torsades de pointes. Although the studies on amiodarone had no reported ventricular arrhythmias, studies on propafenone, sotalol, quinidine, and azimilide reported ventricular arrhythmias. Whereas amiodarone is associated with fewer cardiac side effects, it may cause several, sometimes life-threatening, noncardiac side effects.

Most patients converted to sinus rhythm from atrial fibrillation should not be placed on rhythm maintenance therapy since the risks outweigh the benefits. In a selected group of patients whose quality of life is compromised by atrial fibrillation, the recommended pharmacologic agents for rhythm maintenance are amiodarone, disopyramide, propafenone, and sotalol (drugs listed in alphabetical order). The choice of agent predominantly depends on the specific risk or side effects based on patient characteristics.1 (Grading recommendation: 2A)


AAFP/ACP recently published practice guidelines for the management of patients with AF. A summary of these recommendations is presented here. Several studies have evaluated the treatment of patients with AF. In general, rate control with chronic anticoagulation with warfarin is the recommended strategy for the management of patients with AF. BBs and nondihydropyridine CCBs are effective for rate control during exercise and while at rest. Both pharmacologic and direct-current cardioversion appear to be appropriate rhythm-control strategies. Finally, most patients who have been converted to sinus rhythm should not be placed on rhythm-maintenance therapy.

As always, the final decision should be tailored to individual patients. They should be encouraged to become actively involved in the decision-making process. Together, clinicians and patients should consider all potential benefits and risks.

Dr. Tafreshi is an associate professor of pharmacy and medicine and director of the cardiology pharmacy practice residency at Midwestern University, College of Pharmacy—Glendale (MWU-CPG), Glendale, Ariz. At the time of completion of this article, Drs. Adkins and Hoang were senior pharmacy students at MWU-CPG.

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