Efficacy of class III antiarrhythmics and magnesium combination therapy for atrial fibrillation
Main Article Content
Atrial fibrillation is a common cardiac arrhythmia, and has been a significant financial burden. Class III antiarrhythmics such as dofetilide, ibutilide, and amiodarone are indicated for rhythm control. Magnesium may possess intrinsic antiarrhythmic properties, and may potentially increase the efficacy of class III antiarrhythmics when used concomitantly.
Objective: The purpose of this article is to review the literature on the efficacy of magnesium in addition to Class III antiarrhythmics, specifically amidarone, ibutilide, and dofetilide for the cardioversion of atrial fibrillation.
Methods: Databases Pubmed and CINAHL are utilized along with the search terms amiodarone, dofetilide, ibutlide, magnesium, atrial fibrillation, conversion, rhythm control, and cardioversion.
Results: One study on dofetilide and 5 studies on ibutilide were identified. No studies were found on amiodarone. Patients with atrial fibrillation who received dofetilide and magnesium had higher rates of successful cardioversion as compared to those who only received dofetilide. Conversion rates were similar between the 2 treatment groups for patients with atrial flutter. As for ibutilide, 4 studies have shown that the addition of magnesium significantly increases conversion rates for patients with atrial fibrillation or typical atrial flutter. Conversion rates were similar for patients with atypical atrial flutter. One study showed that addition of magnesium did not improve efficacy of ibutilide. Higher doses of magnesium (4 g) were associated with improved outcomes. Adverse effects of magnesium were mild and included flushing, tingling, and dizziness. Patients who received magnesium had shorter corrected QT intervals and smaller increase in corrected QT interval from baseline.
Compare to previous studies, studies included in this review had higher conversion rates for dofetilide and ibutilide as well as dofetilide and magnesium or ibutilide and magnesium combination therapies. However, only 2 ibutilide studies and 1 dofetilide study reported baseline characteristics such as left atrial size, history of heart failure, and duration of atrial fibrillation, which are significant predictors of successful cardioversion. Therefore, differences in baseline demographics may have influenced the results.
Conclusion: Magnesium may be used as adjunct for dofetilide and ibutilide due to potential improved efficacy and minimal toxicity. Dose ranging studies should be conducted in the future to establish the optimal dose and duration of therapy as well as the optimal serum magnesium concentration in order for the clinician to manage and monitor patients appropriately.
2. American College of Cardiology, American Heart Association, and European Society of Cardiology. 2011 ACCF/AHA/HRS Focused update on the management of patients with atrial fibrillation (updating the 2006 guideline). J Am Coll Cardiol. 2011;57(2):223-242.
3. Khan IA, Mehta NJ, Gowda RM. Amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation. Int J Cardiol. 2003;89(2-3):239-248.
4. Galve E, Rius T, Ballester R, Angeles Artaza M, Arnau JM, Garcia-Dorado D, Soler-Soler J. Intravenous amiodarone in treatment of recent-onset atrial fibrillation: results of a randomized, controlled study. J Am Coll Cardiol. 1996;27(5):1079-1082.
5. Stambler BS, Wood MA, Ellenbogen KA, Perry KT, Wakefield LK, VanderLugt JT. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Circulation. 1996;94(7):1613-1621.
6. Caron MF, Kluger J, Tsikouris JP, Ritvo A, Kalus JS, White CM. Effects of intravenous magnesium sulfate on the QT interval in patients receiving ibutilide. Pharmacotherapy. 2003;23(3):296-300.
7. White CM, Xie J, Chow MSS, Kluger J. Prophylactic Magnesium to Decrease the Arrhythmogenic Potential of Class III Antiarrhythmic Agents in a Rabbit Model. Pharmacotherapy. 1999;19(5):635-640.
8. American Heart Association and the American College of Cardiology Foundation. Prevention of torsade de pointes in hospital settings. J Am Coll Cardiol. 2010;55(9):934-947.
9. Singh S, Zoble RG, Yellen L, Brodsky MA, Feld GK, Berk M, Billing CB. The 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(19):2385-2390.
10. Wolbrette DL. Risk of proarrhythmia with class III antiarrhythmic agents: sex-based differences and other issues. Am J Cardiol. 2003;91(6A):39D-44D.
11. Spearritt D. Torsades de pointes following cardioversion: case history and literature review. Aust Crit Care. 2003;16(4):144-149.
12. Torp-Pedersen C, Møller M, Bloch-Thomsen PE, Køber L, Sandøe E, Egstrup K, Agner E. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. New Engl J Med, 1999;341(12):857-865.
13. Reinhart RA. Clinical correlates of the molecular and cellular actions of magnesium on the cardiovascular system. Am Heart J. 1991;121(5):1513-1521.
14. White RE, Hartzell HC. Magnesium in cardiac function: regulator of ion channels and second messengers. Biochem Pharmacol. 1989;38(6):859-867.
15. Coleman CI, Sood N, Chawla D, Talati R, Ghatak A, Kluger J. Intravenous magnesium sulfate enhances the ability of dofetilide to successfully cardiovert atrial fibrillation or flutter: results of the Dofetilide and Intravenous Magnesium Evaluation. Europace. 2009;11(7):892-895.
16. Kalus JS, Spencer AP, Tsikouris JP, Chung JO, Kenyon KW, Ziska M, Kluger J, White CM. Impact of prophylactic i.v. magnesium on the efficacy of ibutilide for conversion of atrial fibrillation or flutter. Am J Health Syst Pharm. 2003;60(22):2308-2312.
17. Patsilinakos S, Christou A, Kafkas N, Nikolaou N, Antonatos D, Katsanos S, Spanodimos S, Babalis D. Effect of high doses of magnesium on converting ibutilide to a safe and more effective agent. Am J Cardiol. 2010;106(5):673-676.
18. Steinwender C, Hönig S, Kypta A, Kammler J, Schmitt B, Leisch F, Hofmann R. Pre-injection of magnesium sulfate enhances the efficacy of ibutilide for the conversion of typical but not of atypical persistent atrial flutter. Int J Cardiol. 2010;141(3):260-265.
19. Tercius AJ, Kluger J, Coleman CI, White CM. Intravenous magnesium sulfate enhances the ability of intravenous ibutilide to successfully convert atrial fibrillation or flutter. Pacing Clin Electrophysiol. 2007;30(11):1331-1335.
20. Rasmussen HS, Thomsen PE. The electrophysiological effects of intravenous magnesium on human sinus node, atrioventricular node, atrium, and ventricle. Clin Cardiol. 1989;12(2):85-90.
21. Ho KM, Sheridan DJ, Paterson T. Use of intravenous magnesium to treat acute onset atrial fibrillation: a meta-analysis. Heart. 2007;93(11):1433-1440.
22. Onalan O, Crystal E, Daoulah A, Lau C, Crystal A, Lashevsky I. Meta-analysis of magnesium therapy for the acute management of rapid atrial fibrillation. Am J Cardiol. 2007;99(12):1726-1732.
23. Tikosyn® Package Insert. Pfizer Labs. Revised November 2006.
24. Granberry MC. Ibutilide: a new class III antiarrhythmic agent. Am J Health Syst Pharm. 1998;55(3):255-260.
25. Abi-Mansour P, Carberry PA, McCowan RJ, Henthorn RW, Dunn GH, Perry KT. Conversion efficacy and safety of repeated doses of ibutilide in patients with atrial flutter and atrial fibrillation. Am Heart J. 1998;136(4 Pt 1):632-642.
26. Gullestad L, Birkeland K, Mølstad P, Høyer MM, Vanberg P, Kjekshus J. The effect of magnesium versus verapamil on supraventricular arrhythmias. Clin Cardiol. 1993;16(5):429-434.