Treatment of Patients with Atrial Fibrillation

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

Two recently published articles described current recommendationsfor the management of patients with AF.^1,2Whereas one is a review that focuses on AF in general, theother 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 haveitalicized the recommendations from the guidelines. Thesecomments are taken directly from the American Academyof Family Physicians (AAFP) and the American College ofPhysicians (ACP) guidelines for management of patientswith newly detected AF.

These recommendations do not apply to patients withpostoperative or post-myocardial infarction AF, patientswith class IV heart failure, patients already taking antiarrhythmicdrugs, or patients with valvular disease.¹ TheTable³ describes the recommendation gradings.

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

Rhythm Control Versus Rate Control

The Atrial Fibrillation Follow-up Investigation of RhythmManagement (AFFIRM) clinical trial had the greatest influenceon the recommendations of the AAFP/ACP. TheAFFIRM study was a multicenter randomized controlled trialthat enrolled 4060 patients. It was the largest studyreviewed by the AAFP/ACP.² In the AFFIRM trial, patientswere randomly assigned to receive rate-control or rhythm-controltherapy.

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

Other studies that were reviewed by the AAFP/ACPincluded the RAte Control versus Electrical cardioversionfor persistent atrial fibrillation (RACE), the PharmacologicalIntervention in Atrial Fibrillation (PIAF), and the Strategiesof Treatment of Atrial Fibrillation (STAF) trial. Theresearchers concluded that none of these trials demonstratedimprovement in mortality by aggressively controllingrhythm and that rate control with antithrombotic therapyis as effective as rhythm control in many if not mostpatients with AF.²

Rate control with chronic anticoagulation is the recommendedstrategy 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 mortalityand may be inferior in some patient subgroups to rate control.Rhythm control is appropriate when based on other specialconsiderations, such as patient symptoms, exercise tolerance, andpatient preference.¹ (Grading recommendation: 2A)

Anticoagulation

Sixteen studies were evaluated to determine the role ofanticoagulation in patients with AF. According to theAAFP/ACP recommendations, "evidence did not support theuse of low-dose warfarin over other treatments,"includingconventional-dose warfarin.² There is strong evidence forthe use of warfarin in AF patients who have an average orgreater risk for stroke, unless they have an increased risk forbleeding.² Evidence also may support the use of aspirin inwarfarin-ineligible patients who have a lower risk for stroketo manage AF, depending on patients'risks for bleeding.

Patients with atrial fibrillation should receive chronic anticoagulationwith adjusted-dose warfarin, unless they are at low riskof 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 onstudies evaluating digoxin, calcium-channel blockers(CCBs), and beta-blockers (BBs). Digoxin yielded inconsistent results in rate-control studies. When compared withplacebo or digoxin in patients with AF, nondihydropyridineCCBs (verapamil and diltiazem) were effective in reducingventricular rate both at rest and during exercise. The efficacyof BBs in rate control was "agent specific." Atenolol,metoprolol, timolol, pindolol, and nadolol were shown tocontrol ventricular rate both at rest and with exercise. BothCCBs and BBs showed improved efficacy, compared withdigoxin. Some evidence suggests that the addition of digoxinto a BB or nondihydropyridine CCB may provide additionalbenefit over either drug alone.²

Studies of new-onset AF showed that atenolol and metoprololimproved both resting and exercise rate control,whereas other BBs were less consistent. The combination ofdigoxin with diltiazem, atenolol, or betaxolol also was effectiveboth at rest and during exercise. Most of these trialsexcluded 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 invasiveand more efficient with the advent of external biphasicdefibrillators. The immediate efficacy of this method is> 90%. The risk for thromboembolic events does not seemto differ from pharmacologic conversion. Although initiatingantiarrhythmic therapy raises concern for the risk ofdeveloping torsades de pointes due to QT prolongation,side effects of direct-current cardioversion may include skinburns.^1,2 Data do not support the routine use of antiarrhythmicagents before direct-current cardioversion toimprove 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 suchas torsades de pointes. Although the studies on amiodarone had no reportedventricular arrhythmias, studies on propafenone, sotalol, quinidine, andazimilide reported ventricular arrhythmias. Whereas amiodarone is associatedwith 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)

Conclusion

AAFP/ACP recently published practice guidelines for the management ofpatients 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 recommendedstrategy for the management of patients with AF. BBs and nondihydropyridineCCBs are effective for rate control during exercise and while at rest. Bothpharmacologic and direct-current cardioversion appear to be appropriaterhythm-control strategies. Finally, most patients who have been converted tosinus rhythm should not be placed on rhythm-maintenance therapy.

As always, the final decision should be tailored to individual patients. Theyshould be encouraged to become actively involved in the decision-makingprocess. Together, clinicians and patients should consider all potential benefitsand risks.

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

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