Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations
- Kapil Kumar, MD
Kapil Kumar, MD
- Clinical Instructor in Medicine
- Harvard Medical School
- Section Editors
- Peter J Zimetbaum, MD
Peter J Zimetbaum, MD
- Section Editor — Cardiac Arrhythmias
- Professor of Medicine
- Harvard Medical School
- Bradley P Knight, MD, FACC
Bradley P Knight, MD, FACC
- Section Editor — Cardiac Arrhythmias
- Professor of Medicine
- Feinberg School of Medicine, Northwestern University
For patients with atrial fibrillation (AF), there are two main strategies to manage the irregular rhythm and its impact on symptoms: rhythm control (restoration followed by maintenance of sinus rhythm with either antiarrhythmic drugs or catheter ablation); and rate control with atrioventricular (AV) nodal blockers. (See 'Rhythm versus rate control' below.)
For those patients in whom a rhythm control strategy is chosen, the main goal of therapy is to reduce symptoms by decreasing the frequency and duration of episodes as well as the symptoms during recurrences [1,2]. As antiarrhythmic drugs are associated with a potential for serious adverse side effects, particularly the induction of proarrhythmia, they should be prescribed only by practitioners familiar with their use. Patients should be fully informed of both the benefits and risks associated with the use of these drugs. (See 'Drug-related arrhythmias and mortality' below.)
Rhythm control can be achieved with either antiarrhythmic drug therapy or nonpharmacologic methods. This topic provides recommendations for the former. The clinical trials describing the efficacy and toxicity (including proarrhythmia) of the different antiarrhythmic drugs are presented separately. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials".)
Nonpharmacologic methods to maintain sinus rhythm (including surgery and radiofrequency ablation or cryoballoon ablation) in selected patients who are refractory to conventional therapy are discussed elsewhere. (See "Catheter ablation to prevent recurrent atrial fibrillation: Clinical applications" and "Surgical ablation to prevent recurrent atrial fibrillation".)
There are three settings in which a rhythm control strategy for the maintenance of sinus rhythm should be considered :
- Falk RH. Atrial fibrillation. N Engl J Med 2001; 344:1067.
- Connolly SJ. Appropriate outcome measures in trials evaluating treatment of atrial fibrillation. Am Heart J 2000; 139:752.
- 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.
- Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347:1825.
- 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.
- Kühlkamp V, Schirdewan A, Stangl K, et al. Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 2000; 36:139.
- Steeds RP, Birchall AS, Smith M, Channer KS. An open label, randomised, crossover study comparing sotalol and atenolol in the treatment of symptomatic paroxysmal atrial fibrillation. Heart 1999; 82:170.
- Plewan A, Lehmann G, Ndrepepa G, et al. Maintenance of sinus rhythm after electrical cardioversion of persistent atrial fibrillation; sotalol vs bisoprolol. Eur Heart J 2001; 22:1504.
- Tieleman RG, De Langen C, Van Gelder IC, et al. Verapamil reduces tachycardia-induced electrical remodeling of the atria. Circulation 1997; 95:1945.
- Daoud EG, Knight BP, Weiss R, et al. Effect of verapamil and procainamide on atrial fibrillation-induced electrical remodeling in humans. Circulation 1997; 96:1542.
- Bertaglia E, D'Este D, Zerbo F, et al. Effects of verapamil and metoprolol on recovery from atrial electrical remodeling after cardioversion of long-lasting atrial fibrillation. Int J Cardiol 2003; 87:167.
- Wann LS, Curtis AB, January CT, et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (Updating the 2006 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2011; 57:223.
- 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.
- Lafuente-Lafuente C, Mouly S, Longás-Tejero MA, et al. Antiarrhythmic drugs for maintaining sinus rhythm after cardioversion of atrial fibrillation: a systematic review of randomized controlled trials. Arch Intern Med 2006; 166:719.
- Flaker G, Lopes RD, Hylek E, et al. Amiodarone, anticoagulation, and clinical events in patients with atrial fibrillation: insights from the ARISTOTLE trial. J Am Coll Cardiol 2014; 64:1541.
- Coplen SE, Antman EM, Berlin JA, et al. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. A meta-analysis of randomized control trials. Circulation 1990; 82:1106.
- Herweg B, Dalal P, Nagy B, Schweitzer P. Power spectral analysis of heart period variability of preceding sinus rhythm before initiation of paroxysmal atrial fibrillation. Am J Cardiol 1998; 82:869.
- Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC)Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESCEndorsed by the European Stroke Organisation (ESO). Eur Heart J 2016.
- European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace 2010; 12:1360.
- Piccini JP, Hasselblad V, Peterson ED, et al. Comparative efficacy of dronedarone and amiodarone for the maintenance of sinus rhythm in patients with atrial fibrillation. J Am Coll Cardiol 2009; 54:1089.
- Roy D, Talajic M, Dorian P, et al. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med 2000; 342:913.
- Singh BN, Singh SN, Reda DJ, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005; 352:1861.
- 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.
- Goldschlager N, Epstein AE, Naccarelli G, et al. Practical guidelines for clinicians who treat patients with amiodarone. Practice Guidelines Subcommittee, North American Society of Pacing and Electrophysiology. Arch Intern Med 2000; 160:1741.
- Vorperian VR, Havighurst TC, Miller S, January CT. Adverse effects of low dose amiodarone: a meta-analysis. J Am Coll Cardiol 1997; 30:791.
- Zimetbaum P, Josephson ME. Is there a role for maintaining sinus rhythm in patients with atrial fibrillation? Ann Intern Med 2004; 141:720.
- European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010; 31:2369.
- Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324:781.
- Podrid PJ, Anderson JL. Safety and tolerability of long-term propafenone therapy for supraventricular tachyarrhythmias. The Propafenone Multicenter Study Group. Am J Cardiol 1996; 78:430.
- Podrid PJ, Lampert S, Graboys TB, et al. Aggravation of arrhythmia by antiarrhythmic drugs--incidence and predictors. Am J Cardiol 1987; 59:38E.
- Morganroth J, Anderson JL, Gentzkow GD. Classification by type of ventricular arrhythmia predicts frequency of adverse cardiac events from flecainide. J Am Coll Cardiol 1986; 8:607.
- Maisel WH, Kuntz KM, Reimold SC, et al. Risk of initiating antiarrhythmic drug therapy for atrial fibrillation in patients admitted to a university hospital. Ann Intern Med 1997; 127:281.
- Hauser TH, Pinto DS, Josephson ME, Zimetbaum P. Safety and feasibility of a clinical pathway for the outpatient initiation of antiarrhythmic medications in patients with atrial fibrillation or atrial flutter. Am J Cardiol 2003; 91:1437.
- Lafuente-Lafuente C, Longas-Tejero MA, Bergmann JF, Belmin J. Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation. Cochrane Database Syst Rev 2012; :CD005049.
- Kirchhof P, Andresen D, Bosch R, et al. Short-term versus long-term antiarrhythmic drug treatment after cardioversion of atrial fibrillation (Flec-SL): a prospective, randomised, open-label, blinded endpoint assessment trial. Lancet 2012; 380:238.
- Connolly SJ, Camm AJ, Halperin JL, et al. Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med 2011; 365:2268.
- January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:e199.
- January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:2071.
- INITIAL MANAGEMENT DECISIONS
- Rhythm versus rate control
- Addressing precipitating factors
- AV nodal blocker therapy
- Possible role of angiotensin inhibition
- Restoration of sinus rhythm
- SELECTING AN ANTIARRHYTHMIC DRUG
- AF without structural heart disease
- AF associated with structural heart disease
- - Coronary heart disease
- - Heart failure
- - Left ventricular hypertrophy
- Drug-resistant AF
- INPATIENT VERSUS OUTPATIENT INITIATION
- LONG-TERM ISSUES
- AF recurrence
- Drug-related arrhythmias and mortality
- - Proarrhythmia
- - Bradyarrhythmia
- - Ambulatory monitoring
- Short- versus long-term therapy
- Concerns about dronedarone
- RECOMMENDATIONS OF OTHERS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS