decreasing the frequency and duration of episodes. The primary endpoint of many clinical trials involving antiarrhythmic drugs has been time to first recurrence of AF. However, there is great variation in efficacy of antiarrhythmic drugs from patient to patient. Although a drug may be shown to significantly prolong the time to recurrence of AF in a clinical trial, some patients will experience no benefit and others will experience a dramatic reduction in AF frequency. Other outcomes are also important. These include the effect of the drug on overall AF burden, AF episode duration, symptoms, ventricular rate control, and hospitalizations. A single recurrence of AF on a drug does not necessarily indicate treatment failure or require a change in therapy. When the rhythm control strategy is chosen, the recommended drugs for maintenance of sinus rhythm vary with the clinical setting ( table 1 and algorithm 1). Optimal antiarrhythmic drug therapy should be both effective and have a low incidence of toxicity, including proarrhythmia. Amiodarone, sotalol, dofetilide, dronedarone, flecainide, and propafenone are effective in the maintenance of sinus rhythm. Of these, amiodarone is the most effective, but is associated with the development of more frequent side effects. Dronedarone is also associated with the development of significant side effects as well as worse outcomes in some groups of patients with AF. (See 'Amiodarone' above and 'Dronedarone' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. 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. 2. 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. 3. Falk RH. Atrial fibrillation. N Engl J Med 2001; 344:1067. 4. Connolly SJ. Appropriate outcome measures in trials evaluating treatment of atrial fibrillation. Am Heart J 2000; 139:752. https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-clinical-trials/print 12/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - UpToDate 5. 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. 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. 7. 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. 8. Flaker GC, Blackshear JL, McBride R, et al. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol 1992; 20:527. 9. Valembois L, Audureau E, Takeda A, et al. Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation. Cochrane Database Syst Rev 2019; 9:CD005049. 10. S dermark T, Jonsson B, Olsson A, et al. Effect of quinidine on maintaining sinus rhythm after conversion of atrial fibrillation or flutter. A multicentre study from Stockholm. Br Heart J 1975; 37:486. 11. Lloyd EA, Gersh BJ, Forman R. The efficacy of quinidine and disopyramide in the maintenance of sinus rhythm after electroconversion from atrial fibrillation. A double-blind study comparing quinidine, disopyramide and placebo. S Afr Med J 1984; 65:367. 12. Reimold SC, Chalmers TC, Berlin JA, Antman EM. Assessment of the efficacy and safety of antiarrhythmic therapy for chronic atrial fibrillation: observations on the role of trial design and implications of drug-related mortality. Am Heart J 1992; 124:924. 13. Podrid PJ, Lampert S, Graboys TB, et al. Aggravation of arrhythmia by antiarrhythmic drugs incidence and predictors. Am J Cardiol 1987; 59:38E. 14. Karlson BW, Torstensson I, Abj rn C, et al. Disopyramide in the maintenance of sinus rhythm after electroconversion of atrial fibrillation. A placebo-controlled one-year follow-up study. Eur Heart J 1988; 9:284. 15. Szekely P, Sideris DA, Batson GA. Maintenance of sinus rhythm after atrial defibrillation. Br Heart J 1970; 32:741. 16. Madrid AH, Moro C, Mar n-Huerta E, et al. Comparison of flecainide and procainamide in cardioversion of atrial fibrillation. Eur Heart J 1993; 14:1127. https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-clinical-trials/print 13/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - UpToDate 17. Hjelms E. Procainamide conversion of acute atrial fibrillation after open-heart surgery compared with digoxin treatment. Scand J Thorac Cardiovasc Surg 1992; 26:193. 18. Van Gelder IC, Crijns HJ, Van Gilst WH, et al. Efficacy and safety of flecainide acetate in the maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation or atrial flutter. Am J Cardiol 1989; 64:1317. 19. Anderson JL, Gilbert EM, Alpert BL, et al. Prevention of symptomatic recurrences of paroxysmal atrial fibrillation in patients initially tolerating antiarrhythmic therapy. A multicenter, double-blind, crossover study of flecainide and placebo with transtelephonic monitoring. Flecainide Supraventricular Tachycardia Study Group. Circulation 1989; 80:1557. 20. Pritchett EL, McCarthy EA, Wilkinson WE. Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias. A randomized, placebo-controlled, crossover trial in patients tolerating oral therapy. Ann Intern Med 1991; 114:539. 21. A randomized, placebo-controlled trial of propafenone in the prophylaxis of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation. UK Propafenone PSVT Study Group. Circulation 1995; 92:2550. 22. Stroobandt R, Stiels B, Hoebrechts R. Propafenone for conversion and prophylaxis of atrial fibrillation. Propafenone Atrial Fibrillation Trial Investigators. Am J Cardiol 1997; 79:418. 23. Antman EM, Beamer AD, Cantillon C, et al. Therapy of refractory symptomatic atrial fibrillation and atrial flutter: a staged care approach with new antiarrhythmic drugs. J Am Coll Cardiol 1990; 15:698. 24. Geller JC, Geller M, Carlson MD, Waldo AL. Efficacy and safety of moricizine in the maintenance of sinus rhythm in patients with recurrent atrial fibrillation. Am J Cardiol 2001; 87:172. 25. Meinertz T, Lip GY, Lombardi F, et al. Efficacy and safety of propafenone sustained release in the prophylaxis of symptomatic paroxysmal atrial fibrillation (The European Rythmol/Rytmonorm Atrial Fibrillation Trial [ERAFT] Study). Am J Cardiol 2002; 90:1300. 26. Pritchett EL, Page RL, Carlson M, et al. Efficacy and safety of sustained-release propafenone (propafenone SR) for patients with atrial fibrillation. Am J Cardiol 2003; 92:941. 27. Chimienti M, Cullen MT Jr, Casadei G. Safety of long-term flecainide and propafenone in the management of patients with symptomatic paroxysmal atrial fibrillation: report from the Flecainide and Propafenone Italian Study Investigators. Am J Cardiol 1996; 77:60A. 28. Aliot E, Denjoy I. Comparison of the safety and efficacy of flecainide versus propafenone in hospital out-patients with symptomatic paroxysmal atrial fibrillation/flutter. The Flecainide AF French Study Group. Am J Cardiol 1996; 77:66A. https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-clinical-trials/print 14/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - UpToDate 29. Zarembski DG, Nolan PE Jr, Slack MK, Caruso AC. Treatment of resistant atrial fibrillation. A meta-analysis comparing amiodarone and flecainide. Arch Intern Med 1995; 155:1885. 30. Schumacher B, Jung W, Lewalter T, et al. Radiofrequency ablation of atrial flutter due to administration of class IC antiarrhythmic drugs for atrial fibrillation. Am J Cardiol 1999; 83:710. 31. Nabar A, Rodriguez LM, Timmermans C, et al. Radiofrequency ablation of "class IC atrial flutter" in patients with resistant atrial fibrillation. Am J Cardiol 1999; 83:785. 32. 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. 33. 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. 34. 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. 35. Singh BN, Singh SN, Reda DJ, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005; 352:1861. 36. Kochiadakis GE, Igoumenidis NE, Marketou ME, et al. Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study. Heart 2000; 84:251. 37. 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. 38. Dorian P, Mangat I. Restoring sinus rhythm in atrial fibrillation: a Pyrrhic victory? J Am Coll Cardiol 2003; 42:30. 39. Zimetbaum P. Amiodarone for atrial fibrillation. N Engl J Med 2007; 356:935. 40. Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Amiodarone Trials Meta-Analysis Investigators. Lancet 1997; 350:1417. 41. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005; 352:225. 42. Brodsky MA, Allen BJ, Walker CJ 3rd, et al. Amiodarone for maintenance of sinus rhythm after conversion of atrial fibrillation in the setting of a dilated left atrium. Am J Cardiol 1987; 60:572. https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-clinical-trials/print 15/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - UpToDate 43. Gold RL, Haffajee CI, Charos G, et al. Amiodarone for refractory atrial fibrillation. Am J Cardiol 1986; 57:124. 44. Horowitz LN, Spielman SR, Greenspan AM, et al. Use of amiodarone in the treatment of persistent and paroxysmal atrial fibrillation resistant to quinidine therapy. J Am Coll Cardiol 1985; 6:1402. 45. Skoularigis J, R thlisberger C, Skudicky D, et al. Effectiveness of amiodarone and electrical cardioversion for chronic rheumatic atrial fibrillation after mitral valve surgery. Am J Cardiol 1993; 72:423. 46. Gallik DM, Kim SG, Ferrick KJ, et al. Efficacy and safety of sotalol in patients with refractory atrial fibrillation or flutter. Am Heart J 1997; 134:155. 47. Alt E, Ammer R, Lehmann G, et al. Patient characteristics and underlying heart disease as predictors of recurrent atrial fibrillation after internal and external cardioversion in patients treated with oral sotalol. Am Heart J 1997; 134:419. 48. Benditt DG, Williams JH, Jin J, et al. Maintenance of sinus rhythm with oral d,l-sotalol therapy in patients with symptomatic atrial fibrillation and/or atrial flutter. d,l-Sotalol Atrial Fibrillation/Flutter Study Group. Am J Cardiol 1999; 84:270. 49. Reimold SC, Cantillon CO, Friedman PL, Antman EM. Propafenone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Am J Cardiol 1993; 71:558. 50. Bellandi F, Simonetti I, Leoncini M, et al. Long-term efficacy and safety of propafenone and sotalol for the maintenance of sinus rhythm after conversion of recurrent symptomatic atrial fibrillation. Am J Cardiol 2001; 88:640. 51. Singh S, Zoble RG, Yellen L, et al. Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study. Circulation 2000; 102:2385. 52. Ferguson JJ. Meeting highlights. Highlights of the 71st scientific sessions of the American Heart Association. Circulation 1999; 99:2486. 53. Pritchett EL, Wilkinson WE. Effect of dofetilide on survival in patients with supraventricular arrhythmias. Am Heart J 1999; 138:994. 54. Touboul P, Brugada J, Capucci A, et al. Dronedarone for prevention of atrial fibrillation: a dose-ranging study. Eur Heart J 2003; 24:1481. 55. Kathofer S, Thomas D, Karle CA. The novel antiarrhythmic drug dronedarone: comparison with amiodarone. Cardiovasc Drug Rev 2005; 23:217. https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-clinical-trials/print 16/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - UpToDate 56. Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med 2007; 357:987. 57. K ber L, Torp-Pedersen C, McMurray JJ, et al. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med 2008; 358:2678. 58. Hohnloser SH, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med 2009; 360:668. 59. Le Heuzey JY, De Ferrari GM, Radzik D, et al. A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation: the DIONYSOS study. J Cardiovasc Electrophysiol 2010; 21:597. 60. 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. 61. Stambler BS, Wood MA, Ellenbogen KA, et al. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators. Circulation 1996; 94:1613. 62. Nasr IA, Bouzamondo A, Hulot JS, et al. Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis. Eur Heart J 2007; 28:457. 63. Tieleman RG, De Langen C, Van Gelder IC, et al. Verapamil reduces tachycardia-induced electrical remodeling of the atria. Circulation 1997; 95:1945. 64. 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. 65. Van Noord T, Van Gelder IC, Tieleman RG, et al. VERDICT: the Verapamil versus Digoxin Cardioversion Trial: A randomized study on the role of calcium lowering for maintenance of sinus rhythm after cardioversion of persistent atrial fibrillation. J Cardiovasc Electrophysiol 2001; 12:766. 66. Knight BP. Calcium channel blockade for prevention of recurrent atrial fibrillation: have we reached a VERDICT? J Cardiovasc Electrophysiol 2001; 12:770. 67. De Simone A, De Pasquale M, De Matteis C, et al. VErapamil plus antiarrhythmic drugs reduce atrial fibrillation recurrences after an electrical cardioversion (VEPARAF Study). Eur Heart J 2003; 24:1425. 68. Fetsch T, Bauer P, Engberding R, et al. Prevention of atrial fibrillation after cardioversion: results of the PAFAC trial. Eur Heart J 2004; 25:1385. https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-clinical-trials/print 17/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - UpToDate 69. Patten M, Maas R, Bauer P, et al. Suppression of paroxysmal atrial tachyarrhythmias results of the SOPAT trial. Eur Heart J 2004; 25:1395. 70. Zhang Y, Zhang P, Mu Y, et al. The role of renin-angiotensin system blockade therapy in the prevention of atrial fibrillation: a meta-analysis of randomized controlled trials. Clin Pharmacol Ther 2010; 88:521. 71. Frick M, Darp B, Ostergren J, Rosenqvist M. The effect of oral magnesium, alone or as an adjuvant to sotalol, after cardioversion in patients with persistent atrial fibrillation. Eur Heart J 2000; 21:1177. 72. Siu CW, Lau CP, Tse HF. Prevention of atrial fibrillation recurrence by statin therapy in patients with lone atrial fibrillation after successful cardioversion. Am J Cardiol 2003; 92:1343. 73. Fauchier L, Pierre B, de Labriolle A, et al. Antiarrhythmic effect of statin therapy and atrial fibrillation a meta-analysis of randomized controlled trials. J Am Coll Cardiol 2008; 51:828. 74. Young-Xu Y, Jabbour S, Goldberg R, et al. Usefulness of statin drugs in protecting against atrial fibrillation in patients with coronary artery disease. Am J Cardiol 2003; 92:1379. 75. Dotani MI, Elnicki DM, Jain AC, Gibson CM. Effect of preoperative statin therapy and cardiac outcomes after coronary artery bypass grafting. Am J Cardiol 2000; 86:1128. 76. Garc a Seara J, Raposeiras Roubin S, Gude Sampedro F, et al. Failure of hybrid therapy for the prevention of long-term recurrence of atrial fibrillation. Int J Cardiol 2014; 176:74. 77. Anastasio N, Frankel DS, Deyell MW, et al. Nearly uniform failure of atrial flutter ablation and continuation of antiarrhythmic agents (hybrid therapy) for the long-term control of atrial fibrillation. J Interv Card Electrophysiol 2012; 35:57. Topic 1038 Version 37.0 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-clinical-trials/print 18/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - 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-clinical-trials/print 19/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - 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-clinical-trials/print 20/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - UpToDate ACC/AHA/ESC guideline summary: Maintenance of sinus rhythm in atrial fibrillation (AF) Class I - There is evidence and/or general agreement that the following approach is effective for the maintenance of sinus rhythm in patients with AF Treatment of precipitating or reversible causes of AF before initiating therapy with antiarrhythmic drugs. Class IIa - The weight of evidence or opinion is in favor of the usefulness of the following approaches for the maintenance of sinus rhythm in patients with AF Antiarrhythmic drug therapy to maintain sinus rhythm and prevent tachycardia-induced cardiomyopathy. Infrequent, well tolerated recurrent episodes of recurrent AF is reasonable as a successful outcome of antiarrhythmic drug therapy. Outpatient initiation of therapy in patients with no associated heart disease when the antiarrhythmic drug is well tolerated. In patients with lone AF and no structural heart disease, outpatient initiation of propafenone or flecainide therapy in patients with paroxysmal AF who are in sinus rhythm at the time of drug initiation. Sotalol in outpatients in sinus rhythm who have little or no heart disease, are prone to paroxysmal AF, a baseline uncorrected QT interval less than 460 msec, normal serum electrolytes, and no risk factors for class III drug-related proarrhythmia. Catheter ablation as an alternative to antiarrhythmic drug therapy to prevent recurrent AF in symptomatic patients with little or no left atrial enlargement. Class III - There is evidence and/or general agreement that the following approaches are not useful or may be harmful for the maintenance of sinus rhythm in patients with AF Use of a particular antiarrhythmic drug is not recommended in patients with well-defined risk factors for proarrhythmia with that drug. Antiarrhythmic drug therapy is not recommended in patients with advanced sinus node disease or atrioventricular node dysfunction unless they have a functioning electronic cardiac pacemaker. 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 78424 Version 2.0 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-clinical-trials/print 21/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - UpToDate Maintenance of sinus rhythm Therapy to maintain sinus rhythm in patients with recurrent paroxysmal or persistent atrial fibrillation. Drugs are listed alphabetically and not in order of suggested use. The seriousness of heart disease progresses from left to right, and selection of therapy in patients with multiple conditions depends on the most serious condition present. LVH: left ventricular hypertrophy. Reproduced from: Fuster V, Ryden LE, Cannom DS, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial brillation: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. J Am Coll Cardiol 2011; 57:223. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 83173 Version 2.0 https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-clinical-trials/print 22/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - 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-clinical-trials/print 23/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - 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-clinical-trials/print 24/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - 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-clinical-trials/print 25/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - 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-clinical-trials/print 26/27 7/5/23, 9:02 AM Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials - 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. Conflict of interest policy https://www.uptodate.com/contents/antiarrhythmic-drugs-to-maintain-sinus-rhythm-in-patients-with-atrial-fibrillation-clinical-trials/print 27/27