electrocardiogram be obtained after the initiation of antiarrhythmic drug therapy. Short- versus long-term therapy Based on concerns about drug related arrhythmias and the observation that the atrial action potential normalizes after two to four weeks of sinus rhythm (after AF), the concept that short-term therapy might be as effective and safer than long-term therapy has been proposed. This concept was tested in the Flec-SL non-inferiority trial, which randomly assigned 554 patients with persistent AF and who were intended to undergo cardioversion to either four weeks or six months of flecainide (200 to 300 mg per day) [33]. All patients had successful restoration of sinus rhythm and were then followed with daily telemetric electrocardiography (and Holter monitoring whenever AF was noted on two ECGs) for six months. The primary outcome of time to persistent AF or death occurred in 46 and 39 percent of patients, respectively, which did not meet the criteria of non-inferiority. In addition, a post-hoc analysis of patients who had not reached the primary endpoint in the first month found long- term therapy to be superior (Kaplan-Meier estimate of difference 14.3 percent; hazard ratio 0.3; p = 0.0001). We do not consider short-term therapy appropriate for most patients with persistent AF. Concerns about dronedarone Patients with severe heart failure (HF) (generally those with NYHA class III or IV HF, or those who have been hospitalized with HF in the past four weeks) or those with an ejection fraction of <35 percent should not receive dronedarone. (See "The management of atrial fibrillation in patients with heart failure", section on 'Antiarrhythmic drugs'.) The Permanent Atrial fibriLLAtion outcome Study (PALLAS) was designed to test the hypothesis that dronedarone would improve major outcomes in 10,000 patients with permanent AF, over 70 percent of whom had New York Heart Association heart failure class I to III or left ventricular systolic dysfunction at baseline. The rationale was that patients with permanent AF, which affects up to 50 percent of patients with AF, have an increased risk of adverse cardiovascular outcomes including death and myocardial infarction as well as systemic embolization. The ATHENA trial showed a significant reduction in cardiovascular events with dronedarone in patients with paroxysmal or persistent AF. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials", section on 'Dronedarone'.) Patients in PALLAS were treated with standard therapies for AF and then randomly assigned to dronedarone or placebo. The study was stopped early (3236 patients enrolled), after a significantly increased risk (Hazard Ratio 2.29, 95% CI 1.34-3.94) of cardiovascular events https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 12/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate (cardiovascular death, myocardial infarction, stroke and systemic embolism) was observed in the dronedarone arm [34]. The individual secondary end points of stroke, death from cardiovascular causes, and hospitalization for heart failure were also significantly increased in the dronedarone group. (See 'Summary and recommendations' below.) The European Medicines Agency and the United States Food and Drug Agency (USFDA) have advised against the use of dronedarone in patients with permanent AF [35,36]. In addition, the USFDA now recommends that people taking the drug should have an electrocardiogram every three months to make sure that AF has not become permanent. For patients taking dronedarone, routine monitoring of lung and liver function is not mandated by the USFDA; however, periodic monitoring may be reasonable [37]. (See "Clinical uses of dronedarone", section on 'Maintenance of sinus rhythm'.) Follow-up We consider the following approach to follow-up reasonable: We perform an ECG one week after initiation of any antiarrhythmic drug. We typically see patients within three months of initiating a new antiarrhythmic drug to assess efficacy and side effects. This is in addition to commonly performing ambulatory monitoring after drug initiation. Patients are typically seen every 6 to 12 months unless there are particular concerns regarding QT interval prolongation, bradycardia, or other issues identified on the ECG. Specific follow-up recommendations for individual drugs are presented separately. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring" and "Clinical uses of sotalol", section on 'Major side effects' and "Clinical use of dofetilide", section on 'Safety' and "Major side effects of class I antiarrhythmic drugs", section on 'Flecainide' and "Major side effects of class I antiarrhythmic drugs", section on 'Propafenone'.) RECOMMENDATIONS OF OTHERS Our recommendations for the use of antiarrhythmic drugs to maintain sinus rhythm in patients with AF are generally in agreement with recommendations from the American Heart Association/American College of Cardiology/Heart Rhythm Society (2014) and its 2019 focused update, as well as the European Society of Cardiology (2016) [15,38-40]. (See 'Summary and recommendations' below.) SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 13/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topic (see "Patient education: Medicines for atrial fibrillation (The Basics)") SUMMARY AND RECOMMENDATIONS For those patients with atrial fibrillation (AF) in whom a rhythm-control strategy is chosen, the principal goal is to reduce symptoms by decreasing the frequency and duration of episodes [1,2]. (See 'Initial management decisions' above.) Beta blockers are modestly effective in maintaining sinus rhythm and can be tried first in selected patients, such as those without structural heart disease who are concerned about proarrhythmia. (See 'Selecting an antiarrhythmic drug' above.) Compared to placebo, amiodarone, sotalol, dofetilide, dronedarone, flecainide, and propafenone are effective for the maintenance of sinus rhythm, but maintenance rates at one year are significantly less than 75 percent. Amiodarone is consistently more effective than the other antiarrhythmic drugs. (See 'Selecting an antiarrhythmic drug' above.) In addition to less-than-optimal efficacy, serious drug-related adverse side effects limit the use of these drugs. Antiarrhythmic drug therapy should be prescribed only by practitioners familiar with their use. Patients should be fully informed of both the benefits and risks https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 14/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate associated with the use of these drugs. (See 'Drug-related arrhythmias and mortality' above.) Based upon the potential for drug toxicity in the form of induced bradycardia or tachycardia, many patients will need to be hospitalized for continuous electrocardiographic monitoring. Dofetilide must be initiated in a setting with continuous monitoring. (See 'Inpatient versus outpatient initiation' above.) For patients with no structural heart disease and no apparent risk for drug-induced bradycardia or tachycardia, we suggest flecainide or propafenone as the preferred antiarrhythmic drug (Grade 2B). Amiodarone, dofetilide, dronedarone, or sotalol may be used, with sotalol chosen more often by our authors and reviewers. Practitioners should choose only those agents with which they have significant familiarity. (See 'Atrial fibrillation without structural heart disease' above.) For patients with coronary artery disease who do not have advanced heart failure, we suggest dronedarone or sotalol in preference to amiodarone (Grade 2B). Amiodarone is a reasonable choice in patients who prefer its greater efficacy despite its worse extracardiac side-effect profile. (See 'Coronary heart disease' above.) For patients with heart failure, we suggest amiodarone in preference to dofetilide (Grade 2B). Flecainide, propafenone, dronedarone, and sotalol are contraindicated in these patients. (See 'Heart failure' above.) For patients with left ventricular hypertrophy, either amiodarone or dronedarone is generally preferred to other antiarrhythmic agents. Our authors and reviewers have differing approaches, with some choosing amiodarone more often and others choosing dronedarone more often. (See 'Left ventricular hypertrophy' above.) After the initiation of antiarrhythmic drug therapy, screening for drug-associated arrhythmia with ambulatory monitoring should be considered, particularly for patients at high risk of drug-induced arrhythmia. This includes those with baseline bradycardia or borderline QT prolongation, heart failure, or systolic left ventricular dysfunction. (See 'Ambulatory monitoring' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Falk RH. Atrial fibrillation. N Engl J Med 2001; 344:1067. https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 15/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate 2. Connolly SJ. Appropriate outcome measures in trials evaluating treatment of atrial fibrillation. Am Heart J 2000; 139:752. 3. 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. 4. 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. 5. 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. 6. K hlkamp 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. 7. 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. 8. Lafuente-Lafuente C, Mouly S, Long s-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. 9. 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. 10. 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. 11. 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. 12. 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. 13. 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. https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 16/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate 14. 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. 15. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and 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 ESC. Eur Heart J 2021; 42:373. 16. 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. 17. 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. 18. 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. 19. Singh BN, Singh SN, Reda DJ, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005; 352:1861. 20. 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. 21. 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. 22. Vorperian VR, Havighurst TC, Miller S, January CT. Adverse effects of low dose amiodarone: a meta-analysis. J Am Coll Cardiol 1997; 30:791. 23. Zimetbaum P, Josephson ME. Is there a role for maintaining sinus rhythm in patients with atrial fibrillation? Ann Intern Med 2004; 141:720. 24. 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. https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 17/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate 25. 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. 26. 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. 27. Podrid PJ, Lampert S, Graboys TB, et al. Aggravation of arrhythmia by antiarrhythmic drugs incidence and predictors. Am J Cardiol 1987; 59:38E. 28. 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. 29. Reiffel JA, Camm AJ, Belardinelli L, et al. The HARMONY Trial: Combined Ranolazine and Dronedarone in the Management of Paroxysmal Atrial Fibrillation: Mechanistic and Therapeutic Synergism. Circ Arrhythm Electrophysiol 2015; 8:1048. 30. 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. 31. 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. 32. 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. 33. 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. 34. Connolly SJ, Camm AJ, Halperin JL, et al. Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med 2011; 365:2268. 35. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2011/09/new s_detail_001344.jsp&murl=menus/news_and_events/news_and_events.jsp&mid=WC0b01ac0 58004d5c1. 36. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalPro ducts/ucm264204.htm. 37. http://www.fda.gov/Drugs/DrugSafety/ucm240011.htm. 38. 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 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 18/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:e199. 39. 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. 40. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 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 Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019; 140:e125. Topic 1035 Version 60.0 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 19/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate GRAPHICS Rate control versus rhythm control in AFFIRM Results of the AFFIRM trial in which 4060 patients with atrial fibrillation (AF) that was likely to be recurrent were randomly assigned to rhythm or rate control. The primary end point was overall mortality. There was an almost significant trend toward lower mortality with rate control (21.3 versus 23.8 percent, hazard ratio 0.87, 95 percent CI 0.75 to 1.01). Data from Wyse DG, Waldo AL, DiMarco JP, et al. N Engl J Med 2002; 347:1825. Graphic 61608 Version 3.0 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 20/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Rate control versus rhythm control in RACE Results of the RACE trial in which 522 patients with recurrent persistent atrial fibrillation (AF) were randomly assigned to rhythm or rate control. The primary end point was a composite of cardiovascular death, heart failure, thromboembolism, bleeding, pacemaker placement, and antiarrhythmic drug side effects. There was an almost significant trend toward a lower incidence of the primary end point with rate control (17.2 versus 22.6 percent with rhythm control, hazard ratio 0.73, 90 percent CI 0.53 to 1.01). Data from Van Gelder IC, Hagens VE, Bosker HA, et al. N Engl J Med 2002; 347:1834. Graphic 74434 Version 3.0 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 21/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate The rate of recurrent atrial fibrillation is lowest with amiodarone The Canadian Trial of Atrial Fibrillation randomized 403 patients with at least one episode of atrial fibrillation (AF) during the prior six months to low-dose amiodarone, propafenone, or sotalol. After a mean follow-up of 16 months, the likelihood of being free from recurrent AF was highest with amiodarone (65 versus 37 percent for sotalol and propafenone) and the median time to recurrence was longer (>468 versus 98 days). Data from: Roy D, Talajic M, Dorian P, et al. N Engl J Med 2000; 342:913. Graphic 69285 Version 3.0 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 22/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Strategies for rhythm control in patients with paroxysmal* and persistent AF AF: atrial fibrillation; CAD: coronary artery disease; HF: heart failure; LVH: left ventricular hypertrophy; AV: atrioventricular. Catheter ablation is only recommended as first-line therapy for patients with paroxysmal AF (Class IIa recommendation). Drugs are listed alphabetically. Depending on patient preference when performed in experienced centers. Not recommended with severe LVH (wall thickness >1.5 cm). Should be used with caution in patients at risk for torsades de pointes ventricular tachycardia. Should be combined with AV nodal blocking agents. Reproduced from: 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. J Am Coll Cardiol 2014. DOI: 10.1016/j.jacc.2014.03.021. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 95079 Version 3.0 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 23/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Types of proarrhythmia during treatment with antiarrhythmic drugs (AADs) for atrial fibrillation or atrial flutter according to the Vaughan Williams Classification Ventricular proarrhythmia Torsade de pointes (Vaughan Williams class IA and type III drugs) Sustained monomorphic ventricular tachycardia (usually class IC drugs) Sustained polymorphic ventricular tachycardia/ventricular fibrillation without long QT interval (class IA, IC, and III drugs) Atrial proarrhythmia Provocation of recurrence (probably class IA, IC, and III drugs) Conversion of atrial fibrillation (AF) to atrial flutter (usually class IC drugs) with 1:1 conduction Increase of defibrillation threshold (a potential problem with class IC drugs) Abnormalities of conduction or impulse formation Accelerate ventricular rate during AF (class IA and type IC drugs) Accelerate conduction over accessory pathway (digoxin, type IV drugs) Sinus node dysfunction, atrioventricular block (almost all drugs) Vaughan Williams classification of AADs used for the treatment of atrial fibrillation or flutter Class IA - Disopyramide, procainamide, quinidine Class IC - Flecainide, propafenone Class III - Amiodarone, dofetilide, ibutilide, sotalol Class IV - Nondihydropyridine calcium channel blockers (diltiazem and verapamil) Data from Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC guidelines for the management of patients with atrial brillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001 guidelines for the management of patients with atrial brillation). J Am Coll Cardiol 2006; 48:e149. Graphic 66133 Version 4.0 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 24/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Encainide and flecainide increase cardiac mortality Results of the Cardiac Arrhythmia Suppression Trial (CAST) in patients with ventricular premature beats after myocardial infarction. Patients receiving encainide or flecainide had, when compared with those receiving placebo, a significantly lower rate of avoiding a cardiac event (death or resuscitated cardiac arrest) (left panel, p = 0.001) and a lower overall survival (right panel, p = 0.0006). The cause of death was arrhythmia or cardiac arrest. Data from Echt DS, Liebson PR, Mitchell B, et al. N Engl J Med 1991; 324:781. Graphic 59975 Version 5.0 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 25/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Some reported causes and potentiators of the long QT syndrome Congenital Jervell and Lange-Nielsen syndrome (including "channelopathies") Romano-Ward syndrome Idiopathic Acquired Metabolic disorders Other factors Androgen deprivation therapy Hypokalemia Myocardial ischemia or GnRH agonist/antagonist therapy Hypomagnesemia Bilateral surgical orchiectomy infarction, especially with Hypocalcemia Diuretic therapy via electrolyte disorders Starvation particularly hypokalemia and hypomagnesemia prominent T-wave Anorexia nervosa Herbs inversions Liquid protein diets Cinchona (contains quinine), iboga Intracranial Hypothyroidism (ibogaine), licorice extract in overuse via electrolyte disturbances disease Bradyarrhythmias HIV infection Sinus node dysfunction Hypothermia Toxic exposure: Organophosphate AV block: Second or third degree insecticides Medications* High risk Adagrasib Cisaparide Lenvatinib Selpercatinib (restricted availability) Ajmaline Levoketoconazole Sertindole Amiodarone Methadone Sotalol Delamanid Arsenic trioxide Mobocertinib Terfenadine Disopyramide Astemizole Papavirine (intracoronary) Vandetanib Dofetilide Bedaquline Vernakalant Dronedarone Procainamide Bepridil Ziprasidone Haloperidol (IV) Quinidine Chlorpromazine Ibutilide Quinine Ivosidenib Moderate risk Amisulpride (oral) Droperidol Inotuzumab Propafenone ozogamacin Azithromycin Encorafenib Propofol Isoflurane Capecitabine Entrectinib Quetiapine Carbetocin Erythromycin Ribociclib https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 26/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Certinib Escitalopram Levofloxacin Risperidone (systemic) Chloroquine Etelcalcetide Saquinavir Lofexidine Citalopram Fexinidazole Sevoflurane Meglumine antimoniate Clarithromycin Flecainide Sparfloxacin Clofazimine Floxuridine Sunitinib Midostaurin Clomipramine Fluconazole Tegafur Moxifloxacin Clozapine Fluorouracil (systemic) Terbutaline Nilotinib Crizotinib Thioridazine Olanzapine Flupentixol Dabrafenib Toremifene Ondansetrol (IV > Gabobenate Dasatinib Vemurafenib oral) dimeglumine Deslurane Voriconazole Osimertinib Gemifloxacin Domperidone Oxytocin Gilteritinib Doxepin Pazopanib Halofantrine Doxifluridine Pentamidine Haloperidol (oral) Pilsicainide Imipramine Pimozide Piperaquine Probucol Low risk Albuterol Fingolimod Mequitazine Ranolazine (due to bradycardia) Alfuzosin Fluoxetine Methotrimeprazine Relugolix Amisulpride (IV) Fluphenazine Metoclopramide (rare reports) Rilpivirine Amitriptyline Formoterol Metronidazole Romidepsin Anagrelide Foscarnet (systemic) Roxithromycin Apomorphine Fostemsavir Mifepristone Salmeterol Arformoterol Gadofosveset Mirtazapine Sertraline Artemether- Glasdegib Mizolastine lumefantrine Siponimod Goserelin Nelfinavir Asenapine Solifenacin Granisetron Norfloxacin Atomoxetine Sorafenib Hydroxychloroquine Nortriptyline Benperidol (rare reports) Sulpiride Ofloxacin (systemic) Bilastine Hydroxyzine Tacrolimus Olodaterol (systemic) Bosutinib Iloperidone Osilodrostat Tamoxifen Bromperidol Indacaterol Oxaliplatin Telavancin Buprenorphine Itraconazole Ozanimod Telithromycin Buserelin Ketoconazole (systemic) Pacritinib Teneligliptin Ciprofloxacin (Systemic) Lacidipine Paliperidone Tetrabenazine Cocaine (Topical) Lapatinib Panobinostat Trazodone Degarelix Lefamulin Pasireotide Triclabendazole https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 27/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Desipramine Leuprolide Pefloxacin Triptorelin Deutetrabenazine Leuprolide- norethindrone Periciazine Tropisetron Dexmedetomidine** Pimavanserin Vardenafil Levalbuterol Dolasetron Pipamperone Vilanterol Levomethadone Donepezil Pitolisant Vinflunine Lithium Efavirenz Ponesimod Voclosporin Loperamide in Eliglustat Primaquine Vorinostat overdose Eribulin Promazine Zuclopenthixol Lopinavir Ezogabine Radotinib Macimorelin Mefloquine This is not a complete list of all corrected QT interval (QTc)-prolonging drugs and does not include drugs with either a minor degree or isolated association(s) with QTc prolongation that appear to be safe in most patients but may need to be avoided in patients with congenital long QT syndrome depending upon clinical circumstances. A more complete list of such drugs is available at the CredibleMeds website. For clinical use and precautions related to medications and drug interactions, refer to the UpToDate topic review of acquired long QT syndrome discussion of medications and the Lexicomp drug interactions tool. AV: atrioventricular; IV: intravenous; QTc: rate-corrected QT interval on the electrocardiogram. Classifications provided by Lexicomp according to US Food & Drug Administration guidance: Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythic Potential for Non-Antiarrhythmic Drugs Questions and Answers; Guidance for Industry US Food and Drug Administration, June 2017 (revision 2) available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM [1,2] 073161.pdf with additional data from CredibleMeds QT drugs list criteria may lead to some agents being classified differently by other sources. . The use of other classification Not available in the United States. In contrast with other class III antiarrhythmic drugs, amiodarone is rarely associated with torsades de pointes; refer to accompanying text within UpToDate topic reviews of acquired long QT syndrome. Withdrawn from market in most countries due to adverse cardiovascular effects. IV amisulpride antiemetic use is associated with less QTc prolongation than the higher doses administered orally as an antipsychotic. Other cyclic antidepressants may also prolong the QT interval; refer to UpToDate clinical topic on cyclic antidepressant pharmacology, side effects, and separate UpToDate topic on tricyclic antidepressant poisoning. The "low risk" category includes drugs with limited evidence of clinically significant QTc prolongation or TdP risk; many of these drugs have label warnings regarding possible QTc effects or recommendations to avoid use or increase ECG monitoring when combined with other QTc prolonging drugs. https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 28/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Rarely associated with significant QTc prolongation at usual doses for treatment of opioid use disorder, making buprenorphine a suitable alternative for patients with methadone-associated QTc prolongation. Refer to UpToDate clinical topic reviews. * The United States FDA labeling for the sublingual preparation of dexmedetomidine warns against use in patients at elevated risk for QTc prolongation. Both intravenous (ie, sedative) and sublingual formulations of dexmedetomidine have a low risk of QTc prolongation and have not been implicated in TdP. Over-the-counter; available without a prescription. Not associated with significant QTc prolongation in healthy persons. Refer to UpToDate clinical topic for potential adverse cardiovascular (CV) effects in patients with CV disease. Data from: 1. Lexicomp Online. Copyright 1978-2023 Lexicomp, Inc. All Rights Reserved. 2. CredibleMeds QT drugs list website sponsored by Science Foundation of the University of Arizona. Available at http://crediblemeds.org/. Graphic 57431 Version 142.0 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 29/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 30/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-recommendations/print 31/32 7/6/23, 2:50 PM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations - UpToDate Contributor Disclosures Kapil Kumar, MD No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.