Pre-treatment with antiarrhythmic drugs for elective electrical cardioversion of atrial fibrillation: a systematic review and network meta-analysis

Characteristics of included studies.

Study	Design	Setting	Number of patients	Cardioversion	Arms	Follow-up	Risk of bias (acute \| maintenance)
Bianconi et al. 1996³⁰	Single blind	Single centre	100	External cardioversion Synchronized shocks in increasing energy levels (100J, 200J, 300J) until delivery of two 300J shocks	Propafenone: pre-cardioversion, three daily doses of 300 mg, 150 mg, and 300 mg for 48 h; post-cardioversion, ongoing propafenone therapy	N/A	Unclear
Bianconi et al. 1996³⁰	Single blind	Single centre	100		Matching placebo	N/A	Unclear
Boos et al. 2004¹⁸	Unblinded	Single centre	35	External cardioversion Five synchronized monophasic shocks (anterior-anterior: 200J, 360J, and 360J; then, anterior-posterior: 360J, and 360J)	Amiodarone: pre-cardioversion, 1 week of 200 mg PO three times daily; post-cardioversion, 3 weeks of 200 mg PO three times daily for 1 week, followed by 200 mg PO twice daily for 1 week, followed by 200 mg PO daily for 1 week	16 months	Unclear \| high
Boos et al. 2004¹⁸	Unblinded	Single centre	35		No treatment	16 months	Unclear \| high
Capucci 2000³¹	Unblinded	Single centre	92	External cardioversion Seven synchronized shocks (50J, 100J, 150J, 200J, 250J, 300J, and 360J)	Amiodarone: pre-cardioversion, 1 month of 400 mg PO daily; post-cardioversion, 200 mg PO daily	2 months	Unclear \| high
					Glucose-insulin-potassium solution: pre-cardioversion, continuous infusion for 24 h prior to cardioversion
					No treatment
Channer et al. 2004²⁸	Double blind	Multi-centre	161	External cardioversion Five anterolateral synchronized shocks (100J, 200J, 360J, 360J, and 360J) If unsuccessful, one additional anterolateral 360J shock	Amiodarone: pre-cardioversion, 400 mg PO twice daily for 2 weeks; post-cardioversion, 200 mg PO once daily for 8 weeks followed by matching placebo for 44 weeks	52 weeks	High \| high
					Amiodarone: pre-cardioversion, 400 mg PO twice daily for 2 weeks; post-cardioversion, 200 mg PO once daily for 52 weeks
					Matching placebo
Climent et al. 2004³²	Double blind	Single centre	54	External cardioversion Synchronized successive shocks (200J, 300J, and 360J) until technical success or delivery of two 360J shocks	Flecainide: pre-cardioversion, 2 mg/kg IV over 30 min	1 month	High \| high
Climent et al. 2004³²	Double blind	Single centre	54		Matching placebo	1 month	High \| high
De Simone et al. 2003³³	Unblinded	Multi-centre	162	External cardioversion Up to three synchronized external monophasic shocks (200J, 300J, and 360 J) If unsuccessful, internal cardioversion via biphasic shocks in increasing energy levels (5J, 10J, and 30J) until restoration of sinus rhythm	Amiodarone: pre-cardioversion, 600 mg PO daily for 7 days, followed by 400 mg PO daily for 7 days, then 200 mg PO daily for 14 days	3 months	Unclear \| high
De Simone et al. 2003³³	Unblinded	Multi-centre	162		Flecainide: pre-cardioversion, 200 mg PO daily for 3 days	3 months	Unclear \| high
Galperin et al. 2001³⁴	Double blind	Multi-centre	95	External cardioversion Initial shock of 200J and two more shocks of 360J if necessary	Amiodarone: pre-cardioversion, 600 mg PO daily for at least 4 weeks, then 200 mg PO daily	16 months	Unclear \| unclear
Galperin et al. 2001³⁴	Double blind	Multi-centre	95		Matching placebo	16 months	Unclear \| unclear
Hartel et al. 1974³⁵	Double blind	Single centre	52	External cardioversion Initial shock of 100W, followed by 200W and 300W if necessary	Disopyramide: pre-cardioversion, 100 mg PO three times daily starting the day before cardioversion; post-cardioversion, 500 mg PO daily (in 3 doses) for maintenance	3 months	Unclear \| unclear
Hartel et al. 1974³⁵	Double blind	Single centre	52		Matching placebo	3 months	Unclear \| unclear
Hillestad et al. 1972³⁶	Unblinded	Single centre	124	Direct-current cardioversion	Quinidine sulphate: pre-cardioversion, 0.2 g PO twice daily until serum quinidine level of between 4 and 6 mg/L	N/A	Unclear
Hillestad et al. 1972³⁶	Unblinded	Single centre	124	Direct-current cardioversion	No treatment	N/A	Unclear
Jacobs et al. 1998³⁷	Not specified	Single centre	100	Direct-current cardioversion Synchronized shocks at increasing energy levels (50J, 100J, 200J, 360J and 360J) If unsuccessful, the subject was crossed over to the other therapy for another attempt at cardioversion the following day	Procainamide: pre-cardioversion, 15 mg/kg IV (up to max of 1250 mg) over 60 min, followed by continuous infusion of 2 mg/mL prior to cardioversion	N/A	Unclear
Jacobs et al. 1998³⁷	Not specified	Single centre	100		Matching placebo	N/A	Unclear
Jong et al. 1995³⁸	Unblinded	Not specified	91	External cardioversion Four synchronized shocks (100J, 200J, 300J, and 360J)	Amiodarone: pre-cardioversion, 200 mg PO three times daily for 4 weeks; post-cardioversion, 200 mg daily for 1 month then 200 mg every other day for 1 month	2 months	Unclear \| high
Jong et al. 1995³⁸	Unblinded	Not specified	91		Matching placebo	2 months	Unclear \| high
Joseph et al. 2000²¹	Single blind	Multi-centre	120	External cardioversion. Sequential shocks (50J, 100J, 200J, 300J, and 360J) until restoration of sinus rhythm was restored	Amiodarone: pre-cardioversion, 5 mg/kg IV over 30 min then 200 mg PO every 8 h for 6 doses	N/A	Low
					Sotalol: pre-cardioversion, 1.5 mg/kg IV over 30 min then 80 mg PO every 8 h for 6 doses
					No treatment
Kanoupakis et al. 2004³⁹	Unblinded	Not specified	145	Internal cardioversion Intracardiac electrical shock ranging from 3J to a maximum of 15J	Amiodarone: 600 mg PO daily for first 2 weeks then 200 mg daily until end of study	4 weeks	Low \| high
					Carvedilol: 6.25 mg PO twice daily, titrated up to 25 mg twice daily up to end of study
					No treatment
Komatsu et al. 2009⁴⁰	No specified	Single centre	70	External cardioversion Initial anterolateral shock of 150J and another shock of 250 to 350J if necessary	Cibenzoline: 70 mg IV over 5 min	N/A	Unclear
Komatsu et al. 2009⁴⁰	No specified	Single centre	70		Pilsicainide: 50 mg IV over 5 min	N/A	Unclear
Lombardi et al. 2006⁴¹	Double blind	Not specified	658	Direct-current cardioversion	Azimilide: pre-cardioversion, 125 mg PO twice daily for 3 days; post-cardioversion, 125 mg PO daily or placebo daily for 26 weeks	N/A	High
					Sotalol: pre-cardioversion, 160 mg PO twice daily for 3 days; post-cardioversion, 160 mg PO twice daily for 26 weeks
					Matching placebo
Manios etal. 2003⁴²	Unblinded	Single centre	111	Internal cardioversion Intracardiac electrical shocks increasing from 3J to a maximum of 15J in 3J increments	Amiodarone: 600 mg PO daily for 2 weeks, then 200 mg daily up to end of study	6 weeks	Low \| high
					Diltiazem: 270 mg to 360 mg PO daily
					No treatment
Mazzocca et al. 2006⁴³	Unblinded	Single centre	32	Transthoracic biphasic cardioversion Shocks increasing from of 50J to a maximum of 200J (50J, 75J, 100J, 125J, 150J, 200J)	Ibutilide: pre-cardioversion, 0.01 mg/kg IV over 10 min	N/A	Unclear
Mazzocca et al. 2006⁴³	Unblinded	Single centre	32		No treatment	N/A	Unclear
Okishige et al. 2000⁴⁴	Not specified	Single centre	62	External and internal direct-current cardioversion External shocks attempted first at 220J and then at 400J if unsuccessful Intracardiac shock of 50J to 100J if external cardioversion was unsuccessful	Pilsicainide: pre-cardioversion, 150 mg PO daily for 4 weeks; post-cardioversion, 50 mg PO 3 times daily for 2 years	19 months	Unclear \| unclear
Okishige et al. 2000⁴⁴	Not specified	Single centre	62		Matching placebo	19 months	Unclear \| unclear
Oral et al. 1999¹⁹	Unblinded	Single centre	100	Transthoracic cardioversion Step-up protocol of 50J, 100J, 200J, 300J, and 360J	Ibutilide: pre-cardioversion, 1 mg IV over 10 min	6 months	Unclear \| high
Oral et al. 1999¹⁹	Unblinded	Single centre	100		No treatment	6 months	Unclear \| high
Pritchett et al. 2006²²	Double blind	Multi-centre	446	Electrical cardioversion	Azimilide: pre-cardioversion, 125 mg PO twice daily for 3 days; post-cardioversion, 125 mg daily for 6 months	N/A	Unclear
					Matched placebo
					No treatment
Singh et al. 2000⁴⁵	Double blind	Multi-centre	325	Electrical cardioversion	Dofetilide: pre-cardioversion, 125 μg twice daily for a minimum of 3 days or 5 doses; post-cardioversion, 125 μg twice daily for 12 months	12 months	Unclear \| unclear
					Dofetilide: pre-cardioversion, 250 μg twice daily for a minimum of 3 days or 5 doses; post-cardioversion, 125 μg twice daily for 12 months
					Dofetilide: pre-cardioversion, 500 μg twice daily for a minimum of 3 days or 5 doses; post-cardioversion, 125 μg twice daily for 12 months
					Matching placebo
Singh et al. 2005²⁷	Double blind	Multi-centre	665	External cardioversion Up to four standardized monophasic shocks (100J, 200J, 360J, and 360J) Biphasic shocks (150J, 175J, 200J, and 200J) were also used in the final year of the study	Amiodarone: 800 mg PO daily for first 14 days, then 600 mg PO daily for next 14 days, then 300 mg PO daily for first year, then 200 mg PO daily thereafter	1 year	Low \| low
					Sotalol: 80 mg PO twice daily for first week, then 160 mg PO twice daily thereafter
					Matching placebo
Sticherling et al. 2002⁴⁶	Not specified	Single centre	20	Transthoracic cardioversion Step-up protocol with either 100J, 200J, and 360J monophasic shocks or 75J, 120J, 150J, and 200J biphasic shocks If unsuccessful, the alternative study drug was administered, and cardioversion was repeated^a	Verapamil: pre-cardioversion, 0.15 mg/kg IV at rate of 2 mg/min	N/A	Unclear
Sticherling et al. 2002⁴⁶	Not specified	Single centre	20		Ibutilide: pre-cardioversion, 1 mg IV over 10 min	N/A	Unclear
Sticherling et al. 2005⁴⁷	Unblinded	Single centre	20	Transthoracic cardioversion Biphasic shocks of 75J, 120J, 150J, and 200J If unsuccessful, the alternative study drug was administered, and cardioversion was repeated^a	Verapamil: pre-cardioversion, 0.15 mg/kg IV at rate of 2 mg/min	N/A	Unclear
Sticherling et al. 2005⁴⁷	Unblinded	Single centre	20		Amiodarone: pre-cardioversion, 5 mg/kg IV over 5 min	N/A	Unclear
Stroobandt et al. 1997⁴⁸	Double blind	Multi-centre	136	Direct-current cardioversion Initial shock of 200J, subsequent shock of 400J if unsuccessful	Propafenone: pre-cardioversion, 2 mg/kg IV over 30 min followed 2 h later by 150 mg PO every 8 h; post-cardioversion, 150 mg PO 3 times daily for 6 months	6 months	Unclear \| unclear
Stroobandt et al. 1997⁴⁸	Double blind	Multi-centre	136		Matching placebo	6 months	Unclear \| unclear
Thomas et al. 2004²⁰	Unblinded	Single centre	140	Electrical cardioversion	Amiodarone: pre-cardioversion, 10 mg/kg IV amiodarone over 30 min; post-cardioversion, 200 mg PO twice daily until discharge	24 h	Unclear \| high
					Sotalol: pre-cardioversion, 1.5 mg/kg IV over 10 min; post-cardioversion, 80 mg PO twice daily until discharge
					No treatment
Vijayalakshmi et al. 2006⁴⁹	Unblinded	Single centre	94	External cardioversion Monophasic shocks using step-up protocol (100J, 200J, 360J, 360J) If unsuccessful, a final 360J shock was delivered after the administration of atropine	Amiodarone: pre-cardioversion, 200 mg PO three times daily for the first week, twice daily for the second week, and once daily for 4 weeks	6 months	High \| high
					Sotalol: pre-cardioversion, 160 mg PO twice daily for 6 weeks
					No treatment
Villani et al. 2000²³	Single blind	Single centre	120	External cardioversion Synchronized shocks using step-up protocol (50J, 100J, 150J, 200J, 250J, 300J, and 360 J)	Amiodarone: pre-cardioversion, 400 mg PO daily for 1 month; post-cardioversion, 200 mg PO daily	1 month	Unclear \| high
					Diltiazem: pre-cardioversion, 60 mg PO 3 times a day for 1 month (titrated until heart rate <80 beats/min or max dose of 360 mg/day); post-cardioversion, continued at established dose
					Digoxin: pre-cardioversion, 0.25 mg PO daily for 1 month; post-cardioversion, 0.25 mg PO daily

Study	Design	Setting	Number of patients	Cardioversion	Arms	Follow-up	Risk of bias (acute \| maintenance)
Bianconi et al. 1996³⁰	Single blind	Single centre	100	External cardioversion Synchronized shocks in increasing energy levels (100J, 200J, 300J) until delivery of two 300J shocks	Propafenone: pre-cardioversion, three daily doses of 300 mg, 150 mg, and 300 mg for 48 h; post-cardioversion, ongoing propafenone therapy	N/A	Unclear
Bianconi et al. 1996³⁰	Single blind	Single centre	100		Matching placebo	N/A	Unclear
Boos et al. 2004¹⁸	Unblinded	Single centre	35	External cardioversion Five synchronized monophasic shocks (anterior-anterior: 200J, 360J, and 360J; then, anterior-posterior: 360J, and 360J)	Amiodarone: pre-cardioversion, 1 week of 200 mg PO three times daily; post-cardioversion, 3 weeks of 200 mg PO three times daily for 1 week, followed by 200 mg PO twice daily for 1 week, followed by 200 mg PO daily for 1 week	16 months	Unclear \| high
Boos et al. 2004¹⁸	Unblinded	Single centre	35		No treatment	16 months	Unclear \| high
Capucci 2000³¹	Unblinded	Single centre	92	External cardioversion Seven synchronized shocks (50J, 100J, 150J, 200J, 250J, 300J, and 360J)	Amiodarone: pre-cardioversion, 1 month of 400 mg PO daily; post-cardioversion, 200 mg PO daily	2 months	Unclear \| high
					Glucose-insulin-potassium solution: pre-cardioversion, continuous infusion for 24 h prior to cardioversion
					No treatment
Channer et al. 2004²⁸	Double blind	Multi-centre	161	External cardioversion Five anterolateral synchronized shocks (100J, 200J, 360J, 360J, and 360J) If unsuccessful, one additional anterolateral 360J shock	Amiodarone: pre-cardioversion, 400 mg PO twice daily for 2 weeks; post-cardioversion, 200 mg PO once daily for 8 weeks followed by matching placebo for 44 weeks	52 weeks	High \| high
					Amiodarone: pre-cardioversion, 400 mg PO twice daily for 2 weeks; post-cardioversion, 200 mg PO once daily for 52 weeks
					Matching placebo
Climent et al. 2004³²	Double blind	Single centre	54	External cardioversion Synchronized successive shocks (200J, 300J, and 360J) until technical success or delivery of two 360J shocks	Flecainide: pre-cardioversion, 2 mg/kg IV over 30 min	1 month	High \| high
Climent et al. 2004³²	Double blind	Single centre	54		Matching placebo	1 month	High \| high
De Simone et al. 2003³³	Unblinded	Multi-centre	162	External cardioversion Up to three synchronized external monophasic shocks (200J, 300J, and 360 J) If unsuccessful, internal cardioversion via biphasic shocks in increasing energy levels (5J, 10J, and 30J) until restoration of sinus rhythm	Amiodarone: pre-cardioversion, 600 mg PO daily for 7 days, followed by 400 mg PO daily for 7 days, then 200 mg PO daily for 14 days	3 months	Unclear \| high
De Simone et al. 2003³³	Unblinded	Multi-centre	162		Flecainide: pre-cardioversion, 200 mg PO daily for 3 days	3 months	Unclear \| high
Galperin et al. 2001³⁴	Double blind	Multi-centre	95	External cardioversion Initial shock of 200J and two more shocks of 360J if necessary	Amiodarone: pre-cardioversion, 600 mg PO daily for at least 4 weeks, then 200 mg PO daily	16 months	Unclear \| unclear
Galperin et al. 2001³⁴	Double blind	Multi-centre	95		Matching placebo	16 months	Unclear \| unclear
Hartel et al. 1974³⁵	Double blind	Single centre	52	External cardioversion Initial shock of 100W, followed by 200W and 300W if necessary	Disopyramide: pre-cardioversion, 100 mg PO three times daily starting the day before cardioversion; post-cardioversion, 500 mg PO daily (in 3 doses) for maintenance	3 months	Unclear \| unclear
Hartel et al. 1974³⁵	Double blind	Single centre	52		Matching placebo	3 months	Unclear \| unclear
Hillestad et al. 1972³⁶	Unblinded	Single centre	124	Direct-current cardioversion	Quinidine sulphate: pre-cardioversion, 0.2 g PO twice daily until serum quinidine level of between 4 and 6 mg/L	N/A	Unclear
Hillestad et al. 1972³⁶	Unblinded	Single centre	124	Direct-current cardioversion	No treatment	N/A	Unclear
Jacobs et al. 1998³⁷	Not specified	Single centre	100	Direct-current cardioversion Synchronized shocks at increasing energy levels (50J, 100J, 200J, 360J and 360J) If unsuccessful, the subject was crossed over to the other therapy for another attempt at cardioversion the following day	Procainamide: pre-cardioversion, 15 mg/kg IV (up to max of 1250 mg) over 60 min, followed by continuous infusion of 2 mg/mL prior to cardioversion	N/A	Unclear
Jacobs et al. 1998³⁷	Not specified	Single centre	100		Matching placebo	N/A	Unclear
Jong et al. 1995³⁸	Unblinded	Not specified	91	External cardioversion Four synchronized shocks (100J, 200J, 300J, and 360J)	Amiodarone: pre-cardioversion, 200 mg PO three times daily for 4 weeks; post-cardioversion, 200 mg daily for 1 month then 200 mg every other day for 1 month	2 months	Unclear \| high
Jong et al. 1995³⁸	Unblinded	Not specified	91		Matching placebo	2 months	Unclear \| high
Joseph et al. 2000²¹	Single blind	Multi-centre	120	External cardioversion. Sequential shocks (50J, 100J, 200J, 300J, and 360J) until restoration of sinus rhythm was restored	Amiodarone: pre-cardioversion, 5 mg/kg IV over 30 min then 200 mg PO every 8 h for 6 doses	N/A	Low
					Sotalol: pre-cardioversion, 1.5 mg/kg IV over 30 min then 80 mg PO every 8 h for 6 doses
					No treatment
Kanoupakis et al. 2004³⁹	Unblinded	Not specified	145	Internal cardioversion Intracardiac electrical shock ranging from 3J to a maximum of 15J	Amiodarone: 600 mg PO daily for first 2 weeks then 200 mg daily until end of study	4 weeks	Low \| high
					Carvedilol: 6.25 mg PO twice daily, titrated up to 25 mg twice daily up to end of study
					No treatment
Komatsu et al. 2009⁴⁰	No specified	Single centre	70	External cardioversion Initial anterolateral shock of 150J and another shock of 250 to 350J if necessary	Cibenzoline: 70 mg IV over 5 min	N/A	Unclear
Komatsu et al. 2009⁴⁰	No specified	Single centre	70		Pilsicainide: 50 mg IV over 5 min	N/A	Unclear
Lombardi et al. 2006⁴¹	Double blind	Not specified	658	Direct-current cardioversion	Azimilide: pre-cardioversion, 125 mg PO twice daily for 3 days; post-cardioversion, 125 mg PO daily or placebo daily for 26 weeks	N/A	High
					Sotalol: pre-cardioversion, 160 mg PO twice daily for 3 days; post-cardioversion, 160 mg PO twice daily for 26 weeks
					Matching placebo
Manios etal. 2003⁴²	Unblinded	Single centre	111	Internal cardioversion Intracardiac electrical shocks increasing from 3J to a maximum of 15J in 3J increments	Amiodarone: 600 mg PO daily for 2 weeks, then 200 mg daily up to end of study	6 weeks	Low \| high
					Diltiazem: 270 mg to 360 mg PO daily
					No treatment
Mazzocca et al. 2006⁴³	Unblinded	Single centre	32	Transthoracic biphasic cardioversion Shocks increasing from of 50J to a maximum of 200J (50J, 75J, 100J, 125J, 150J, 200J)	Ibutilide: pre-cardioversion, 0.01 mg/kg IV over 10 min	N/A	Unclear
Mazzocca et al. 2006⁴³	Unblinded	Single centre	32		No treatment	N/A	Unclear
Okishige et al. 2000⁴⁴	Not specified	Single centre	62	External and internal direct-current cardioversion External shocks attempted first at 220J and then at 400J if unsuccessful Intracardiac shock of 50J to 100J if external cardioversion was unsuccessful	Pilsicainide: pre-cardioversion, 150 mg PO daily for 4 weeks; post-cardioversion, 50 mg PO 3 times daily for 2 years	19 months	Unclear \| unclear
Okishige et al. 2000⁴⁴	Not specified	Single centre	62		Matching placebo	19 months	Unclear \| unclear
Oral et al. 1999¹⁹	Unblinded	Single centre	100	Transthoracic cardioversion Step-up protocol of 50J, 100J, 200J, 300J, and 360J	Ibutilide: pre-cardioversion, 1 mg IV over 10 min	6 months	Unclear \| high
Oral et al. 1999¹⁹	Unblinded	Single centre	100		No treatment	6 months	Unclear \| high
Pritchett et al. 2006²²	Double blind	Multi-centre	446	Electrical cardioversion	Azimilide: pre-cardioversion, 125 mg PO twice daily for 3 days; post-cardioversion, 125 mg daily for 6 months	N/A	Unclear
					Matched placebo
					No treatment
Singh et al. 2000⁴⁵	Double blind	Multi-centre	325	Electrical cardioversion	Dofetilide: pre-cardioversion, 125 μg twice daily for a minimum of 3 days or 5 doses; post-cardioversion, 125 μg twice daily for 12 months	12 months	Unclear \| unclear
					Dofetilide: pre-cardioversion, 250 μg twice daily for a minimum of 3 days or 5 doses; post-cardioversion, 125 μg twice daily for 12 months
					Dofetilide: pre-cardioversion, 500 μg twice daily for a minimum of 3 days or 5 doses; post-cardioversion, 125 μg twice daily for 12 months
					Matching placebo
Singh et al. 2005²⁷	Double blind	Multi-centre	665	External cardioversion Up to four standardized monophasic shocks (100J, 200J, 360J, and 360J) Biphasic shocks (150J, 175J, 200J, and 200J) were also used in the final year of the study	Amiodarone: 800 mg PO daily for first 14 days, then 600 mg PO daily for next 14 days, then 300 mg PO daily for first year, then 200 mg PO daily thereafter	1 year	Low \| low
					Sotalol: 80 mg PO twice daily for first week, then 160 mg PO twice daily thereafter
					Matching placebo
Sticherling et al. 2002⁴⁶	Not specified	Single centre	20	Transthoracic cardioversion Step-up protocol with either 100J, 200J, and 360J monophasic shocks or 75J, 120J, 150J, and 200J biphasic shocks If unsuccessful, the alternative study drug was administered, and cardioversion was repeated^a	Verapamil: pre-cardioversion, 0.15 mg/kg IV at rate of 2 mg/min	N/A	Unclear
Sticherling et al. 2002⁴⁶	Not specified	Single centre	20		Ibutilide: pre-cardioversion, 1 mg IV over 10 min	N/A	Unclear
Sticherling et al. 2005⁴⁷	Unblinded	Single centre	20	Transthoracic cardioversion Biphasic shocks of 75J, 120J, 150J, and 200J If unsuccessful, the alternative study drug was administered, and cardioversion was repeated^a	Verapamil: pre-cardioversion, 0.15 mg/kg IV at rate of 2 mg/min	N/A	Unclear
Sticherling et al. 2005⁴⁷	Unblinded	Single centre	20		Amiodarone: pre-cardioversion, 5 mg/kg IV over 5 min	N/A	Unclear
Stroobandt et al. 1997⁴⁸	Double blind	Multi-centre	136	Direct-current cardioversion Initial shock of 200J, subsequent shock of 400J if unsuccessful	Propafenone: pre-cardioversion, 2 mg/kg IV over 30 min followed 2 h later by 150 mg PO every 8 h; post-cardioversion, 150 mg PO 3 times daily for 6 months	6 months	Unclear \| unclear
Stroobandt et al. 1997⁴⁸	Double blind	Multi-centre	136		Matching placebo	6 months	Unclear \| unclear
Thomas et al. 2004²⁰	Unblinded	Single centre	140	Electrical cardioversion	Amiodarone: pre-cardioversion, 10 mg/kg IV amiodarone over 30 min; post-cardioversion, 200 mg PO twice daily until discharge	24 h	Unclear \| high
					Sotalol: pre-cardioversion, 1.5 mg/kg IV over 10 min; post-cardioversion, 80 mg PO twice daily until discharge
					No treatment
Vijayalakshmi et al. 2006⁴⁹	Unblinded	Single centre	94	External cardioversion Monophasic shocks using step-up protocol (100J, 200J, 360J, 360J) If unsuccessful, a final 360J shock was delivered after the administration of atropine	Amiodarone: pre-cardioversion, 200 mg PO three times daily for the first week, twice daily for the second week, and once daily for 4 weeks	6 months	High \| high
					Sotalol: pre-cardioversion, 160 mg PO twice daily for 6 weeks
					No treatment
Villani et al. 2000²³	Single blind	Single centre	120	External cardioversion Synchronized shocks using step-up protocol (50J, 100J, 150J, 200J, 250J, 300J, and 360 J)	Amiodarone: pre-cardioversion, 400 mg PO daily for 1 month; post-cardioversion, 200 mg PO daily	1 month	Unclear \| high
					Diltiazem: pre-cardioversion, 60 mg PO 3 times a day for 1 month (titrated until heart rate <80 beats/min or max dose of 360 mg/day); post-cardioversion, continued at established dose
					Digoxin: pre-cardioversion, 0.25 mg PO daily for 1 month; post-cardioversion, 0.25 mg PO daily

a

We did not include post-crossover results in our analysis.

Table 1

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Characteristics of included studies.

Study	Design	Setting	Number of patients	Cardioversion	Arms	Follow-up	Risk of bias (acute \| maintenance)
Bianconi et al. 1996³⁰	Single blind	Single centre	100	External cardioversion Synchronized shocks in increasing energy levels (100J, 200J, 300J) until delivery of two 300J shocks	Propafenone: pre-cardioversion, three daily doses of 300 mg, 150 mg, and 300 mg for 48 h; post-cardioversion, ongoing propafenone therapy	N/A	Unclear
Bianconi et al. 1996³⁰	Single blind	Single centre	100		Matching placebo	N/A	Unclear
Boos et al. 2004¹⁸	Unblinded	Single centre	35	External cardioversion Five synchronized monophasic shocks (anterior-anterior: 200J, 360J, and 360J; then, anterior-posterior: 360J, and 360J)	Amiodarone: pre-cardioversion, 1 week of 200 mg PO three times daily; post-cardioversion, 3 weeks of 200 mg PO three times daily for 1 week, followed by 200 mg PO twice daily for 1 week, followed by 200 mg PO daily for 1 week	16 months	Unclear \| high
Boos et al. 2004¹⁸	Unblinded	Single centre	35		No treatment	16 months	Unclear \| high
Capucci 2000³¹	Unblinded	Single centre	92	External cardioversion Seven synchronized shocks (50J, 100J, 150J, 200J, 250J, 300J, and 360J)	Amiodarone: pre-cardioversion, 1 month of 400 mg PO daily; post-cardioversion, 200 mg PO daily	2 months	Unclear \| high
					Glucose-insulin-potassium solution: pre-cardioversion, continuous infusion for 24 h prior to cardioversion
					No treatment
Channer et al. 2004²⁸	Double blind	Multi-centre	161	External cardioversion Five anterolateral synchronized shocks (100J, 200J, 360J, 360J, and 360J) If unsuccessful, one additional anterolateral 360J shock	Amiodarone: pre-cardioversion, 400 mg PO twice daily for 2 weeks; post-cardioversion, 200 mg PO once daily for 8 weeks followed by matching placebo for 44 weeks	52 weeks	High \| high
					Amiodarone: pre-cardioversion, 400 mg PO twice daily for 2 weeks; post-cardioversion, 200 mg PO once daily for 52 weeks
					Matching placebo
Climent et al. 2004³²	Double blind	Single centre	54	External cardioversion Synchronized successive shocks (200J, 300J, and 360J) until technical success or delivery of two 360J shocks	Flecainide: pre-cardioversion, 2 mg/kg IV over 30 min	1 month	High \| high
Climent et al. 2004³²	Double blind	Single centre	54		Matching placebo	1 month	High \| high
De Simone et al. 2003³³	Unblinded	Multi-centre	162	External cardioversion Up to three synchronized external monophasic shocks (200J, 300J, and 360 J) If unsuccessful, internal cardioversion via biphasic shocks in increasing energy levels (5J, 10J, and 30J) until restoration of sinus rhythm	Amiodarone: pre-cardioversion, 600 mg PO daily for 7 days, followed by 400 mg PO daily for 7 days, then 200 mg PO daily for 14 days	3 months	Unclear \| high
De Simone et al. 2003³³	Unblinded	Multi-centre	162		Flecainide: pre-cardioversion, 200 mg PO daily for 3 days	3 months	Unclear \| high
Galperin et al. 2001³⁴	Double blind	Multi-centre	95	External cardioversion Initial shock of 200J and two more shocks of 360J if necessary	Amiodarone: pre-cardioversion, 600 mg PO daily for at least 4 weeks, then 200 mg PO daily	16 months	Unclear \| unclear
Galperin et al. 2001³⁴	Double blind	Multi-centre	95		Matching placebo	16 months	Unclear \| unclear
Hartel et al. 1974³⁵	Double blind	Single centre	52	External cardioversion Initial shock of 100W, followed by 200W and 300W if necessary	Disopyramide: pre-cardioversion, 100 mg PO three times daily starting the day before cardioversion; post-cardioversion, 500 mg PO daily (in 3 doses) for maintenance	3 months	Unclear \| unclear
Hartel et al. 1974³⁵	Double blind	Single centre	52		Matching placebo	3 months	Unclear \| unclear
Hillestad et al. 1972³⁶	Unblinded	Single centre	124	Direct-current cardioversion	Quinidine sulphate: pre-cardioversion, 0.2 g PO twice daily until serum quinidine level of between 4 and 6 mg/L	N/A	Unclear
Hillestad et al. 1972³⁶	Unblinded	Single centre	124	Direct-current cardioversion	No treatment	N/A	Unclear
Jacobs et al. 1998³⁷	Not specified	Single centre	100	Direct-current cardioversion Synchronized shocks at increasing energy levels (50J, 100J, 200J, 360J and 360J) If unsuccessful, the subject was crossed over to the other therapy for another attempt at cardioversion the following day	Procainamide: pre-cardioversion, 15 mg/kg IV (up to max of 1250 mg) over 60 min, followed by continuous infusion of 2 mg/mL prior to cardioversion	N/A	Unclear
Jacobs et al. 1998³⁷	Not specified	Single centre	100		Matching placebo	N/A	Unclear
Jong et al. 1995³⁸	Unblinded	Not specified	91	External cardioversion Four synchronized shocks (100J, 200J, 300J, and 360J)	Amiodarone: pre-cardioversion, 200 mg PO three times daily for 4 weeks; post-cardioversion, 200 mg daily for 1 month then 200 mg every other day for 1 month	2 months	Unclear \| high
Jong et al. 1995³⁸	Unblinded	Not specified	91		Matching placebo	2 months	Unclear \| high
Joseph et al. 2000²¹	Single blind	Multi-centre	120	External cardioversion. Sequential shocks (50J, 100J, 200J, 300J, and 360J) until restoration of sinus rhythm was restored	Amiodarone: pre-cardioversion, 5 mg/kg IV over 30 min then 200 mg PO every 8 h for 6 doses	N/A	Low
					Sotalol: pre-cardioversion, 1.5 mg/kg IV over 30 min then 80 mg PO every 8 h for 6 doses
					No treatment
Kanoupakis et al. 2004³⁹	Unblinded	Not specified	145	Internal cardioversion Intracardiac electrical shock ranging from 3J to a maximum of 15J	Amiodarone: 600 mg PO daily for first 2 weeks then 200 mg daily until end of study	4 weeks	Low \| high
					Carvedilol: 6.25 mg PO twice daily, titrated up to 25 mg twice daily up to end of study
					No treatment
Komatsu et al. 2009⁴⁰	No specified	Single centre	70	External cardioversion Initial anterolateral shock of 150J and another shock of 250 to 350J if necessary	Cibenzoline: 70 mg IV over 5 min	N/A	Unclear
Komatsu et al. 2009⁴⁰	No specified	Single centre	70		Pilsicainide: 50 mg IV over 5 min	N/A	Unclear
Lombardi et al. 2006⁴¹	Double blind	Not specified	658	Direct-current cardioversion	Azimilide: pre-cardioversion, 125 mg PO twice daily for 3 days; post-cardioversion, 125 mg PO daily or placebo daily for 26 weeks	N/A	High
					Sotalol: pre-cardioversion, 160 mg PO twice daily for 3 days; post-cardioversion, 160 mg PO twice daily for 26 weeks
					Matching placebo
Manios etal. 2003⁴²	Unblinded	Single centre	111	Internal cardioversion Intracardiac electrical shocks increasing from 3J to a maximum of 15J in 3J increments	Amiodarone: 600 mg PO daily for 2 weeks, then 200 mg daily up to end of study	6 weeks	Low \| high
					Diltiazem: 270 mg to 360 mg PO daily
					No treatment
Mazzocca et al. 2006⁴³	Unblinded	Single centre	32	Transthoracic biphasic cardioversion Shocks increasing from of 50J to a maximum of 200J (50J, 75J, 100J, 125J, 150J, 200J)	Ibutilide: pre-cardioversion, 0.01 mg/kg IV over 10 min	N/A	Unclear
Mazzocca et al. 2006⁴³	Unblinded	Single centre	32		No treatment	N/A	Unclear
Okishige et al. 2000⁴⁴	Not specified	Single centre	62	External and internal direct-current cardioversion External shocks attempted first at 220J and then at 400J if unsuccessful Intracardiac shock of 50J to 100J if external cardioversion was unsuccessful	Pilsicainide: pre-cardioversion, 150 mg PO daily for 4 weeks; post-cardioversion, 50 mg PO 3 times daily for 2 years	19 months	Unclear \| unclear
Okishige et al. 2000⁴⁴	Not specified	Single centre	62		Matching placebo	19 months	Unclear \| unclear
Oral et al. 1999¹⁹	Unblinded	Single centre	100	Transthoracic cardioversion Step-up protocol of 50J, 100J, 200J, 300J, and 360J	Ibutilide: pre-cardioversion, 1 mg IV over 10 min	6 months	Unclear \| high
Oral et al. 1999¹⁹	Unblinded	Single centre	100		No treatment	6 months	Unclear \| high
Pritchett et al. 2006²²	Double blind	Multi-centre	446	Electrical cardioversion	Azimilide: pre-cardioversion, 125 mg PO twice daily for 3 days; post-cardioversion, 125 mg daily for 6 months	N/A	Unclear
					Matched placebo
					No treatment
Singh et al. 2000⁴⁵	Double blind	Multi-centre	325	Electrical cardioversion	Dofetilide: pre-cardioversion, 125 μg twice daily for a minimum of 3 days or 5 doses; post-cardioversion, 125 μg twice daily for 12 months	12 months	Unclear \| unclear
					Dofetilide: pre-cardioversion, 250 μg twice daily for a minimum of 3 days or 5 doses; post-cardioversion, 125 μg twice daily for 12 months
					Dofetilide: pre-cardioversion, 500 μg twice daily for a minimum of 3 days or 5 doses; post-cardioversion, 125 μg twice daily for 12 months
					Matching placebo
Singh et al. 2005²⁷	Double blind	Multi-centre	665	External cardioversion Up to four standardized monophasic shocks (100J, 200J, 360J, and 360J) Biphasic shocks (150J, 175J, 200J, and 200J) were also used in the final year of the study	Amiodarone: 800 mg PO daily for first 14 days, then 600 mg PO daily for next 14 days, then 300 mg PO daily for first year, then 200 mg PO daily thereafter	1 year	Low \| low
					Sotalol: 80 mg PO twice daily for first week, then 160 mg PO twice daily thereafter
					Matching placebo
Sticherling et al. 2002⁴⁶	Not specified	Single centre	20	Transthoracic cardioversion Step-up protocol with either 100J, 200J, and 360J monophasic shocks or 75J, 120J, 150J, and 200J biphasic shocks If unsuccessful, the alternative study drug was administered, and cardioversion was repeated^a	Verapamil: pre-cardioversion, 0.15 mg/kg IV at rate of 2 mg/min	N/A	Unclear
Sticherling et al. 2002⁴⁶	Not specified	Single centre	20		Ibutilide: pre-cardioversion, 1 mg IV over 10 min	N/A	Unclear
Sticherling et al. 2005⁴⁷	Unblinded	Single centre	20	Transthoracic cardioversion Biphasic shocks of 75J, 120J, 150J, and 200J If unsuccessful, the alternative study drug was administered, and cardioversion was repeated^a	Verapamil: pre-cardioversion, 0.15 mg/kg IV at rate of 2 mg/min	N/A	Unclear
Sticherling et al. 2005⁴⁷	Unblinded	Single centre	20		Amiodarone: pre-cardioversion, 5 mg/kg IV over 5 min	N/A	Unclear
Stroobandt et al. 1997⁴⁸	Double blind	Multi-centre	136	Direct-current cardioversion Initial shock of 200J, subsequent shock of 400J if unsuccessful	Propafenone: pre-cardioversion, 2 mg/kg IV over 30 min followed 2 h later by 150 mg PO every 8 h; post-cardioversion, 150 mg PO 3 times daily for 6 months	6 months	Unclear \| unclear
Stroobandt et al. 1997⁴⁸	Double blind	Multi-centre	136		Matching placebo	6 months	Unclear \| unclear
Thomas et al. 2004²⁰	Unblinded	Single centre	140	Electrical cardioversion	Amiodarone: pre-cardioversion, 10 mg/kg IV amiodarone over 30 min; post-cardioversion, 200 mg PO twice daily until discharge	24 h	Unclear \| high
					Sotalol: pre-cardioversion, 1.5 mg/kg IV over 10 min; post-cardioversion, 80 mg PO twice daily until discharge
					No treatment
Vijayalakshmi et al. 2006⁴⁹	Unblinded	Single centre	94	External cardioversion Monophasic shocks using step-up protocol (100J, 200J, 360J, 360J) If unsuccessful, a final 360J shock was delivered after the administration of atropine	Amiodarone: pre-cardioversion, 200 mg PO three times daily for the first week, twice daily for the second week, and once daily for 4 weeks	6 months	High \| high
					Sotalol: pre-cardioversion, 160 mg PO twice daily for 6 weeks
					No treatment
Villani et al. 2000²³	Single blind	Single centre	120	External cardioversion Synchronized shocks using step-up protocol (50J, 100J, 150J, 200J, 250J, 300J, and 360 J)	Amiodarone: pre-cardioversion, 400 mg PO daily for 1 month; post-cardioversion, 200 mg PO daily	1 month	Unclear \| high
					Diltiazem: pre-cardioversion, 60 mg PO 3 times a day for 1 month (titrated until heart rate <80 beats/min or max dose of 360 mg/day); post-cardioversion, continued at established dose
					Digoxin: pre-cardioversion, 0.25 mg PO daily for 1 month; post-cardioversion, 0.25 mg PO daily

Study	Design	Setting	Number of patients	Cardioversion	Arms	Follow-up	Risk of bias (acute \| maintenance)
Bianconi et al. 1996³⁰	Single blind	Single centre	100	External cardioversion Synchronized shocks in increasing energy levels (100J, 200J, 300J) until delivery of two 300J shocks	Propafenone: pre-cardioversion, three daily doses of 300 mg, 150 mg, and 300 mg for 48 h; post-cardioversion, ongoing propafenone therapy	N/A	Unclear
Bianconi et al. 1996³⁰	Single blind	Single centre	100		Matching placebo	N/A	Unclear
Boos et al. 2004¹⁸	Unblinded	Single centre	35	External cardioversion Five synchronized monophasic shocks (anterior-anterior: 200J, 360J, and 360J; then, anterior-posterior: 360J, and 360J)	Amiodarone: pre-cardioversion, 1 week of 200 mg PO three times daily; post-cardioversion, 3 weeks of 200 mg PO three times daily for 1 week, followed by 200 mg PO twice daily for 1 week, followed by 200 mg PO daily for 1 week	16 months	Unclear \| high
Boos et al. 2004¹⁸	Unblinded	Single centre	35		No treatment	16 months	Unclear \| high
Capucci 2000³¹	Unblinded	Single centre	92	External cardioversion Seven synchronized shocks (50J, 100J, 150J, 200J, 250J, 300J, and 360J)	Amiodarone: pre-cardioversion, 1 month of 400 mg PO daily; post-cardioversion, 200 mg PO daily	2 months	Unclear \| high
					Glucose-insulin-potassium solution: pre-cardioversion, continuous infusion for 24 h prior to cardioversion
					No treatment
Channer et al. 2004²⁸	Double blind	Multi-centre	161	External cardioversion Five anterolateral synchronized shocks (100J, 200J, 360J, 360J, and 360J) If unsuccessful, one additional anterolateral 360J shock	Amiodarone: pre-cardioversion, 400 mg PO twice daily for 2 weeks; post-cardioversion, 200 mg PO once daily for 8 weeks followed by matching placebo for 44 weeks	52 weeks	High \| high
					Amiodarone: pre-cardioversion, 400 mg PO twice daily for 2 weeks; post-cardioversion, 200 mg PO once daily for 52 weeks
					Matching placebo
Climent et al. 2004³²	Double blind	Single centre	54	External cardioversion Synchronized successive shocks (200J, 300J, and 360J) until technical success or delivery of two 360J shocks	Flecainide: pre-cardioversion, 2 mg/kg IV over 30 min	1 month	High \| high
Climent et al. 2004³²	Double blind	Single centre	54		Matching placebo	1 month	High \| high
De Simone et al. 2003³³	Unblinded	Multi-centre	162	External cardioversion Up to three synchronized external monophasic shocks (200J, 300J, and 360 J) If unsuccessful, internal cardioversion via biphasic shocks in increasing energy levels (5J, 10J, and 30J) until restoration of sinus rhythm	Amiodarone: pre-cardioversion, 600 mg PO daily for 7 days, followed by 400 mg PO daily for 7 days, then 200 mg PO daily for 14 days	3 months	Unclear \| high
De Simone et al. 2003³³	Unblinded	Multi-centre	162		Flecainide: pre-cardioversion, 200 mg PO daily for 3 days	3 months	Unclear \| high
Galperin et al. 2001³⁴	Double blind	Multi-centre	95	External cardioversion Initial shock of 200J and two more shocks of 360J if necessary	Amiodarone: pre-cardioversion, 600 mg PO daily for at least 4 weeks, then 200 mg PO daily	16 months	Unclear \| unclear
Galperin et al. 2001³⁴	Double blind	Multi-centre	95		Matching placebo	16 months	Unclear \| unclear
Hartel et al. 1974³⁵	Double blind	Single centre	52	External cardioversion Initial shock of 100W, followed by 200W and 300W if necessary	Disopyramide: pre-cardioversion, 100 mg PO three times daily starting the day before cardioversion; post-cardioversion, 500 mg PO daily (in 3 doses) for maintenance	3 months	Unclear \| unclear
Hartel et al. 1974³⁵	Double blind	Single centre	52		Matching placebo	3 months	Unclear \| unclear
Hillestad et al. 1972³⁶	Unblinded	Single centre	124	Direct-current cardioversion	Quinidine sulphate: pre-cardioversion, 0.2 g PO twice daily until serum quinidine level of between 4 and 6 mg/L	N/A	Unclear
Hillestad et al. 1972³⁶	Unblinded	Single centre	124	Direct-current cardioversion	No treatment	N/A	Unclear
Jacobs et al. 1998³⁷	Not specified	Single centre	100	Direct-current cardioversion Synchronized shocks at increasing energy levels (50J, 100J, 200J, 360J and 360J) If unsuccessful, the subject was crossed over to the other therapy for another attempt at cardioversion the following day	Procainamide: pre-cardioversion, 15 mg/kg IV (up to max of 1250 mg) over 60 min, followed by continuous infusion of 2 mg/mL prior to cardioversion	N/A	Unclear
Jacobs et al. 1998³⁷	Not specified	Single centre	100		Matching placebo	N/A	Unclear
Jong et al. 1995³⁸	Unblinded	Not specified	91	External cardioversion Four synchronized shocks (100J, 200J, 300J, and 360J)	Amiodarone: pre-cardioversion, 200 mg PO three times daily for 4 weeks; post-cardioversion, 200 mg daily for 1 month then 200 mg every other day for 1 month	2 months	Unclear \| high
Jong et al. 1995³⁸	Unblinded	Not specified	91		Matching placebo	2 months	Unclear \| high
Joseph et al. 2000²¹	Single blind	Multi-centre	120	External cardioversion. Sequential shocks (50J, 100J, 200J, 300J, and 360J) until restoration of sinus rhythm was restored	Amiodarone: pre-cardioversion, 5 mg/kg IV over 30 min then 200 mg PO every 8 h for 6 doses	N/A	Low
					Sotalol: pre-cardioversion, 1.5 mg/kg IV over 30 min then 80 mg PO every 8 h for 6 doses
					No treatment
Kanoupakis et al. 2004³⁹	Unblinded	Not specified	145	Internal cardioversion Intracardiac electrical shock ranging from 3J to a maximum of 15J	Amiodarone: 600 mg PO daily for first 2 weeks then 200 mg daily until end of study	4 weeks	Low \| high
					Carvedilol: 6.25 mg PO twice daily, titrated up to 25 mg twice daily up to end of study
					No treatment
Komatsu et al. 2009⁴⁰	No specified	Single centre	70	External cardioversion Initial anterolateral shock of 150J and another shock of 250 to 350J if necessary	Cibenzoline: 70 mg IV over 5 min	N/A	Unclear
Komatsu et al. 2009⁴⁰	No specified	Single centre	70		Pilsicainide: 50 mg IV over 5 min	N/A	Unclear
Lombardi et al. 2006⁴¹	Double blind	Not specified	658	Direct-current cardioversion	Azimilide: pre-cardioversion, 125 mg PO twice daily for 3 days; post-cardioversion, 125 mg PO daily or placebo daily for 26 weeks	N/A	High
					Sotalol: pre-cardioversion, 160 mg PO twice daily for 3 days; post-cardioversion, 160 mg PO twice daily for 26 weeks
					Matching placebo
Manios etal. 2003⁴²	Unblinded	Single centre	111	Internal cardioversion Intracardiac electrical shocks increasing from 3J to a maximum of 15J in 3J increments	Amiodarone: 600 mg PO daily for 2 weeks, then 200 mg daily up to end of study	6 weeks	Low \| high
					Diltiazem: 270 mg to 360 mg PO daily
					No treatment
Mazzocca et al. 2006⁴³	Unblinded	Single centre	32	Transthoracic biphasic cardioversion Shocks increasing from of 50J to a maximum of 200J (50J, 75J, 100J, 125J, 150J, 200J)	Ibutilide: pre-cardioversion, 0.01 mg/kg IV over 10 min	N/A	Unclear
Mazzocca et al. 2006⁴³	Unblinded	Single centre	32		No treatment	N/A	Unclear
Okishige et al. 2000⁴⁴	Not specified	Single centre	62	External and internal direct-current cardioversion External shocks attempted first at 220J and then at 400J if unsuccessful Intracardiac shock of 50J to 100J if external cardioversion was unsuccessful	Pilsicainide: pre-cardioversion, 150 mg PO daily for 4 weeks; post-cardioversion, 50 mg PO 3 times daily for 2 years	19 months	Unclear \| unclear
Okishige et al. 2000⁴⁴	Not specified	Single centre	62		Matching placebo	19 months	Unclear \| unclear
Oral et al. 1999¹⁹	Unblinded	Single centre	100	Transthoracic cardioversion Step-up protocol of 50J, 100J, 200J, 300J, and 360J	Ibutilide: pre-cardioversion, 1 mg IV over 10 min	6 months	Unclear \| high
Oral et al. 1999¹⁹	Unblinded	Single centre	100		No treatment	6 months	Unclear \| high
Pritchett et al. 2006²²	Double blind	Multi-centre	446	Electrical cardioversion	Azimilide: pre-cardioversion, 125 mg PO twice daily for 3 days; post-cardioversion, 125 mg daily for 6 months	N/A	Unclear
					Matched placebo
					No treatment
Singh et al. 2000⁴⁵	Double blind	Multi-centre	325	Electrical cardioversion	Dofetilide: pre-cardioversion, 125 μg twice daily for a minimum of 3 days or 5 doses; post-cardioversion, 125 μg twice daily for 12 months	12 months	Unclear \| unclear
					Dofetilide: pre-cardioversion, 250 μg twice daily for a minimum of 3 days or 5 doses; post-cardioversion, 125 μg twice daily for 12 months
					Dofetilide: pre-cardioversion, 500 μg twice daily for a minimum of 3 days or 5 doses; post-cardioversion, 125 μg twice daily for 12 months
					Matching placebo
Singh et al. 2005²⁷	Double blind	Multi-centre	665	External cardioversion Up to four standardized monophasic shocks (100J, 200J, 360J, and 360J) Biphasic shocks (150J, 175J, 200J, and 200J) were also used in the final year of the study	Amiodarone: 800 mg PO daily for first 14 days, then 600 mg PO daily for next 14 days, then 300 mg PO daily for first year, then 200 mg PO daily thereafter	1 year	Low \| low
					Sotalol: 80 mg PO twice daily for first week, then 160 mg PO twice daily thereafter
					Matching placebo
Sticherling et al. 2002⁴⁶	Not specified	Single centre	20	Transthoracic cardioversion Step-up protocol with either 100J, 200J, and 360J monophasic shocks or 75J, 120J, 150J, and 200J biphasic shocks If unsuccessful, the alternative study drug was administered, and cardioversion was repeated^a	Verapamil: pre-cardioversion, 0.15 mg/kg IV at rate of 2 mg/min	N/A	Unclear
Sticherling et al. 2002⁴⁶	Not specified	Single centre	20		Ibutilide: pre-cardioversion, 1 mg IV over 10 min	N/A	Unclear
Sticherling et al. 2005⁴⁷	Unblinded	Single centre	20	Transthoracic cardioversion Biphasic shocks of 75J, 120J, 150J, and 200J If unsuccessful, the alternative study drug was administered, and cardioversion was repeated^a	Verapamil: pre-cardioversion, 0.15 mg/kg IV at rate of 2 mg/min	N/A	Unclear
Sticherling et al. 2005⁴⁷	Unblinded	Single centre	20		Amiodarone: pre-cardioversion, 5 mg/kg IV over 5 min	N/A	Unclear
Stroobandt et al. 1997⁴⁸	Double blind	Multi-centre	136	Direct-current cardioversion Initial shock of 200J, subsequent shock of 400J if unsuccessful	Propafenone: pre-cardioversion, 2 mg/kg IV over 30 min followed 2 h later by 150 mg PO every 8 h; post-cardioversion, 150 mg PO 3 times daily for 6 months	6 months	Unclear \| unclear
Stroobandt et al. 1997⁴⁸	Double blind	Multi-centre	136		Matching placebo	6 months	Unclear \| unclear
Thomas et al. 2004²⁰	Unblinded	Single centre	140	Electrical cardioversion	Amiodarone: pre-cardioversion, 10 mg/kg IV amiodarone over 30 min; post-cardioversion, 200 mg PO twice daily until discharge	24 h	Unclear \| high
					Sotalol: pre-cardioversion, 1.5 mg/kg IV over 10 min; post-cardioversion, 80 mg PO twice daily until discharge
					No treatment
Vijayalakshmi et al. 2006⁴⁹	Unblinded	Single centre	94	External cardioversion Monophasic shocks using step-up protocol (100J, 200J, 360J, 360J) If unsuccessful, a final 360J shock was delivered after the administration of atropine	Amiodarone: pre-cardioversion, 200 mg PO three times daily for the first week, twice daily for the second week, and once daily for 4 weeks	6 months	High \| high
					Sotalol: pre-cardioversion, 160 mg PO twice daily for 6 weeks
					No treatment
Villani et al. 2000²³	Single blind	Single centre	120	External cardioversion Synchronized shocks using step-up protocol (50J, 100J, 150J, 200J, 250J, 300J, and 360 J)	Amiodarone: pre-cardioversion, 400 mg PO daily for 1 month; post-cardioversion, 200 mg PO daily	1 month	Unclear \| high
					Diltiazem: pre-cardioversion, 60 mg PO 3 times a day for 1 month (titrated until heart rate <80 beats/min or max dose of 360 mg/day); post-cardioversion, continued at established dose
					Digoxin: pre-cardioversion, 0.25 mg PO daily for 1 month; post-cardioversion, 0.25 mg PO daily

a

We did not include post-crossover results in our analysis.

For the acute restoration of sinus rhythm outcome, 20 of 28 studies had an unclear risk of bias with four studies each having a low and high risk of bias (see Table 1 and Supplementary material online, Appendix S2). For the maintenance of sinus rhythm outcome, 12 of 18 studies had a high risk of bias, and one study had a low risk of bias. The most common reason for an unclear risk of bias was an inadequate description of the randomization protocol (9 of 21 acute restoration studies and 4 of 5 long-term maintenance studies). For the maintenance of sinus rhythm outcome, lack of blinding of participants, personnel and/or outcome assessment was the most common cause of high risk of bias (9 of 12 studies).

Pre-treatment regimens

Table 1 details the treatment regimens used prior to electrical cardioversion. Class Ia regimens included disopyramide, procainamide, quinidine, and cibenzoline. Class Ic regimens were flecainide, propafenone, and pilsicainide. Class III regimens included sotalol, ibutilide, azimilide, and dofetilide. Dosing regimens for amiodarone ranged from 5 mg/kg IV over 5–30 min to 200–800 mg PO daily for 1–6 weeks.

Acute restoration of sinus rhythm

The number of trials included in direct comparisons varied from 1 to 13 (Table 3). Figure 1A is the network diagram for acute restoration of sinus rhythm. An indirect estimate was not generated for Class III vs. no treatment or rate control because the studies that comprised the network loop were the same three-arm trials that informed the direct comparison.

Figure 1

Network diagram of acute restoration and maintenance of sinus rhythm. The size of each node is proportional to the number of participants. The size of each edge reflects the number of studies for that comparison.

Table 3

SUCRA values for five-node analysis

Anti-arrhythmic drug	Sucra
Acute restoration
Amiodarone	0.83
Class III	0.76
Class Ia	0.50
Class Ic	0.31
No treatment or rate control	0.10
Long-term maintenance
Amiodarone	0.93
Class Ia	0.63
Class Ic	0.52
Class III	0.41
No treatment or rate control	0.01

Anti-arrhythmic drug	Sucra
Acute restoration
Amiodarone	0.83
Class III	0.76
Class Ia	0.50
Class Ic	0.31
No treatment or rate control	0.10
Long-term maintenance
Amiodarone	0.93
Class Ia	0.63
Class Ic	0.52
Class III	0.41
No treatment or rate control	0.01

SUCRA, surface under the cumulative ranking curve.

Table 3

SUCRA values for five-node analysis

Anti-arrhythmic drug	Sucra
Acute restoration
Amiodarone	0.83
Class III	0.76
Class Ia	0.50
Class Ic	0.31
No treatment or rate control	0.10
Long-term maintenance
Amiodarone	0.93
Class Ia	0.63
Class Ic	0.52
Class III	0.41
No treatment or rate control	0.01

Anti-arrhythmic drug	Sucra
Acute restoration
Amiodarone	0.83
Class III	0.76
Class Ia	0.50
Class Ic	0.31
No treatment or rate control	0.10
Long-term maintenance
Amiodarone	0.93
Class Ia	0.63
Class Ic	0.52
Class III	0.41
No treatment or rate control	0.01

SUCRA, surface under the cumulative ranking curve.

Table 2

Network meta-analysis results of five-node analysis, including confidence assessments

Comparison	Trials with direct comparisons (n)	Direct estimate (95% CI)	Indirect estimate (95% CrI)	NMA estimate (95% CrI)	Overall certainty
Acute restoration of sinus rhythm
Class Ia vs. no treatment or rate control	3	1.04 (0.38, 2.89)	8.10 (1.22, 55.69)	1.65 (0.65, 4.24)	High
Class Ic vs. no treatment or rate control	4	1.54 (0.60, 4.02)	0.81 (0.17, 3.88)	1.30 (0.59, 2.96)	High
Class III vs. no treatment or rate control	10	2.41 (1.37, 4.62)	N/A*	2.41 (1.37, 4.62)	High
Amiodarone vs. no treatment or rate control	13	2.82 (1.61, 4.98)	0.80 (0.07, 8.89)	2.58 (1.54, 4.37)	High
Class Ic vs. Class Ia	1	0.21 (0.04, 1.22)	1.67 (0.47, 6.46)	0.79 (0.26, 2.38)	High
Amiodarone vs. Class Ic	1	0.74 (0.08, 6.94)	2.40 (0.88, 6.76)	1.97 (0.79, 5.02)	High
Amiodarone vs. Class III	4	0.75 (0.25, 2.11)	1.45 (0.43, 4.01)	1.07 (0.50, 2.12)	High
Long-term maintenance of sinus rhythm
Class Ia vs. no treatment or rate control	1	3.52 (0.94, 14.08)	N/A*	3.52 (0.94, 14.08)	High
Class Ic vs. no treatment or rate control	3	1.91 (0.96, 4.08)	4.71 (2.03, 11.03)	2.83 (1.60, 5.10)	Moderate
Class III vs. no treatment or rate control	5	2.50 (1.70, 3.79)	N/A*	2.50 (1.70, 3.79)	High
Amiodarone vs. no treatment or rate control	11	5.86 (4.09, 8.42)	2.37 (0.68, 8.33)	5.37 (4.00, 7.39)	High
Amiodarone vs. Class Ic	1	1.22 (0.55, 2.81)	3.08 (1.38, 6.48)	1.89 (1.05, 3.45)	Moderate
Amiodarone vs. Class III	3	2.31 (1.21, 4.18)	1.97 (0.88, 4.46)	2.19 (1.39, 3.26)	High

Comparison	Trials with direct comparisons (n)	Direct estimate (95% CI)	Indirect estimate (95% CrI)	NMA estimate (95% CrI)	Overall certainty
Acute restoration of sinus rhythm
Class Ia vs. no treatment or rate control	3	1.04 (0.38, 2.89)	8.10 (1.22, 55.69)	1.65 (0.65, 4.24)	High
Class Ic vs. no treatment or rate control	4	1.54 (0.60, 4.02)	0.81 (0.17, 3.88)	1.30 (0.59, 2.96)	High
Class III vs. no treatment or rate control	10	2.41 (1.37, 4.62)	N/A*	2.41 (1.37, 4.62)	High
Amiodarone vs. no treatment or rate control	13	2.82 (1.61, 4.98)	0.80 (0.07, 8.89)	2.58 (1.54, 4.37)	High
Class Ic vs. Class Ia	1	0.21 (0.04, 1.22)	1.67 (0.47, 6.46)	0.79 (0.26, 2.38)	High
Amiodarone vs. Class Ic	1	0.74 (0.08, 6.94)	2.40 (0.88, 6.76)	1.97 (0.79, 5.02)	High
Amiodarone vs. Class III	4	0.75 (0.25, 2.11)	1.45 (0.43, 4.01)	1.07 (0.50, 2.12)	High
Long-term maintenance of sinus rhythm
Class Ia vs. no treatment or rate control	1	3.52 (0.94, 14.08)	N/A*	3.52 (0.94, 14.08)	High
Class Ic vs. no treatment or rate control	3	1.91 (0.96, 4.08)	4.71 (2.03, 11.03)	2.83 (1.60, 5.10)	Moderate
Class III vs. no treatment or rate control	5	2.50 (1.70, 3.79)	N/A*	2.50 (1.70, 3.79)	High
Amiodarone vs. no treatment or rate control	11	5.86 (4.09, 8.42)	2.37 (0.68, 8.33)	5.37 (4.00, 7.39)	High
Amiodarone vs. Class Ic	1	1.22 (0.55, 2.81)	3.08 (1.38, 6.48)	1.89 (1.05, 3.45)	Moderate
Amiodarone vs. Class III	3	2.31 (1.21, 4.18)	1.97 (0.88, 4.46)	2.19 (1.39, 3.26)	High

CI, confidence interval; CrI, credible interval; N/A, not applicable.

Table 2

Network meta-analysis results of five-node analysis, including confidence assessments

Comparison	Trials with direct comparisons (n)	Direct estimate (95% CI)	Indirect estimate (95% CrI)	NMA estimate (95% CrI)	Overall certainty
Acute restoration of sinus rhythm
Class Ia vs. no treatment or rate control	3	1.04 (0.38, 2.89)	8.10 (1.22, 55.69)	1.65 (0.65, 4.24)	High
Class Ic vs. no treatment or rate control	4	1.54 (0.60, 4.02)	0.81 (0.17, 3.88)	1.30 (0.59, 2.96)	High
Class III vs. no treatment or rate control	10	2.41 (1.37, 4.62)	N/A*	2.41 (1.37, 4.62)	High
Amiodarone vs. no treatment or rate control	13	2.82 (1.61, 4.98)	0.80 (0.07, 8.89)	2.58 (1.54, 4.37)	High
Class Ic vs. Class Ia	1	0.21 (0.04, 1.22)	1.67 (0.47, 6.46)	0.79 (0.26, 2.38)	High
Amiodarone vs. Class Ic	1	0.74 (0.08, 6.94)	2.40 (0.88, 6.76)	1.97 (0.79, 5.02)	High
Amiodarone vs. Class III	4	0.75 (0.25, 2.11)	1.45 (0.43, 4.01)	1.07 (0.50, 2.12)	High
Long-term maintenance of sinus rhythm
Class Ia vs. no treatment or rate control	1	3.52 (0.94, 14.08)	N/A*	3.52 (0.94, 14.08)	High
Class Ic vs. no treatment or rate control	3	1.91 (0.96, 4.08)	4.71 (2.03, 11.03)	2.83 (1.60, 5.10)	Moderate
Class III vs. no treatment or rate control	5	2.50 (1.70, 3.79)	N/A*	2.50 (1.70, 3.79)	High
Amiodarone vs. no treatment or rate control	11	5.86 (4.09, 8.42)	2.37 (0.68, 8.33)	5.37 (4.00, 7.39)	High
Amiodarone vs. Class Ic	1	1.22 (0.55, 2.81)	3.08 (1.38, 6.48)	1.89 (1.05, 3.45)	Moderate
Amiodarone vs. Class III	3	2.31 (1.21, 4.18)	1.97 (0.88, 4.46)	2.19 (1.39, 3.26)	High

Comparison	Trials with direct comparisons (n)	Direct estimate (95% CI)	Indirect estimate (95% CrI)	NMA estimate (95% CrI)	Overall certainty
Acute restoration of sinus rhythm
Class Ia vs. no treatment or rate control	3	1.04 (0.38, 2.89)	8.10 (1.22, 55.69)	1.65 (0.65, 4.24)	High
Class Ic vs. no treatment or rate control	4	1.54 (0.60, 4.02)	0.81 (0.17, 3.88)	1.30 (0.59, 2.96)	High
Class III vs. no treatment or rate control	10	2.41 (1.37, 4.62)	N/A*	2.41 (1.37, 4.62)	High
Amiodarone vs. no treatment or rate control	13	2.82 (1.61, 4.98)	0.80 (0.07, 8.89)	2.58 (1.54, 4.37)	High
Class Ic vs. Class Ia	1	0.21 (0.04, 1.22)	1.67 (0.47, 6.46)	0.79 (0.26, 2.38)	High
Amiodarone vs. Class Ic	1	0.74 (0.08, 6.94)	2.40 (0.88, 6.76)	1.97 (0.79, 5.02)	High
Amiodarone vs. Class III	4	0.75 (0.25, 2.11)	1.45 (0.43, 4.01)	1.07 (0.50, 2.12)	High
Long-term maintenance of sinus rhythm
Class Ia vs. no treatment or rate control	1	3.52 (0.94, 14.08)	N/A*	3.52 (0.94, 14.08)	High
Class Ic vs. no treatment or rate control	3	1.91 (0.96, 4.08)	4.71 (2.03, 11.03)	2.83 (1.60, 5.10)	Moderate
Class III vs. no treatment or rate control	5	2.50 (1.70, 3.79)	N/A*	2.50 (1.70, 3.79)	High
Amiodarone vs. no treatment or rate control	11	5.86 (4.09, 8.42)	2.37 (0.68, 8.33)	5.37 (4.00, 7.39)	High
Amiodarone vs. Class Ic	1	1.22 (0.55, 2.81)	3.08 (1.38, 6.48)	1.89 (1.05, 3.45)	Moderate
Amiodarone vs. Class III	3	2.31 (1.21, 4.18)	1.97 (0.88, 4.46)	2.19 (1.39, 3.26)	High

CI, confidence interval; CrI, credible interval; N/A, not applicable.

In absolute terms, the unadjusted average rate of acute conversion in the no treatment or rate control arm was 74.8% (1210/1618). For Classes Ia, Ic, and III AADs, the unadjusted success rates were 81.1% (163/201), 80.7% (276/342), and 83.7% (1145/1368), respectively. The absolute conversion rate for amiodarone was 83.3% (729/875).

Table 2 lists the results of the NMA. Compared with no treatment or rate control, amiodarone and Class III AADs were associated with increased restoration of sinus rhythm: Class III (OR: 2.41; CrI: 1.37–4.62, high certainty); and amiodarone (OR: 2.58; CrI: 1.54–4.37, high certainty). No AAD class was associated with increased odds of cardioversion compared with one another.

According to SUCRA (Table 3), amiodarone (0.81) and Class III AADs (0.73) were most likely to be the best intervention when compared with Class Ia (0.59) and Ic (0.30) AADs and no treatment or rate control (0.07).

Results were consistent between direct and indirect comparisons for all analyses. Although the direction of effect differed between direct and indirect estimates for two comparisons—i.e. Class Ic and amiodarone vs. no treatment or rate control (see Supplementary material online, Appendix S3)—no comparison met the a priori established threshold of P < 0.05 in the node-splitting analysis for inconsistency (see Supplementary material online, Appendix).

Long-term maintenance of sinus rhythm

The number of trials included in direct comparisons ranged from 1 to 11 and the mean duration of follow-up was 7 months (range: 24 h to 18.7 months), (Table 2). Figure 1B is the network diagram for this outcome. An indirect estimate was not generated for two comparisons: Class Ia and Class III vs. no treatment or rate control. Class Ia had a single comparison with no treatment or rate control. An indirect estimate was not generated for Class III vs. no treatment or rate control because the studies that comprised the network loop were the same three-arm trials that informed the direct comparison.

The unadjusted proportion of patients who maintained sinus rhythm in the no treatment or rate control arm was 28.9% (260/900). For Classes Ia, Ic, and III AADs, the unadjusted success rates were 50.0% (13/26), 43.2% (112/259), and 39.5% (250/633), respectively. The absolute maintenance rate for amiodarone was 58.0% (477/822).

Except for Class Ia (OR: 3.52; CrI: 0.94–14.08, high certainty), the other AAD groups were associated with significantly increased odds (see Table 3) of maintaining sinus rhythm when compared with no treatment or rate control: Class Ic (OR: 2.83; CrI: 1.60–5.10, moderate certainty), Class III (OR: 2.50; CrI: 1.70–3.79, high certainty) and amiodarone (OR: 5.37; CrI: 4.00–7.39, high certainty).

Amiodarone was associated with higher odds when compared with Class Ic (OR: 1.89; CrI: 1.05–3.45, moderate certainty) and Class III (OR: 2.19; CrI: 1.39–3.26, high certainty) AADs. SUCRA results were consistent with these findings (see Table 2). Amiodarone ranked first for this outcome (0.93)—followed by Class Ia (0.64), Class Ic (0.52), Class III (0.41), and no treatment or rate control (0.008).

Node-splitting analysis and visual inspection of the forest plot did not demonstrate inconsistency between direct and indirect estimates for all comparisons regarding maintenance of sinus rhythm (see Supplementary material online, Appendix 3).

Assessment of certainty of evidence

We assessed the evidence for all comparisons to be of high certainty for acute restoration of sinus rhythm (see Table 2).²⁴ The certainty for direct and indirect estimates varied between moderate and high.

For maintenance of sinus rhythm, we assessed 4 comparisons to be of high certainty and two to be of moderate certainty (see Table 2). The certainty of evidence for comparisons between Class Ic and no treatment or rate control, and amiodarone was downgraded for serious risk of bias because each comparison was driven by a study with high risk of bias for inconsistent reporting of results and lack of blinding, respectively.

Discussion

In patients with AF undergoing electrical cardioversion, pre-treatment with amiodarone and Class III AADs both enhance the acute restoration of sinus rhythm with comparable efficacy. For the long-term maintenance of sinus rhythm, amiodarone is most likely to have benefit, but other Class III AADs and Class Ic AADs are also effective.

The current guidelines for AF published by the American College of Cardiology provides a Class I recommendation for repeated attempts at cardioversion and includes a brief phrase regarding AAD administration prior to repeat cardioversion—citing a single RCT included in this review and mentioning only ibutilide.^19,25 The Canadian Cardiovascular Society makes a similar recommendation based on a single RCT and mentions only amiodarone and ibutilide.²⁶ Based on several individual RCTs that are included in this review, the European Society of Cardiology provides a Class IIa recommendation to specifically consider amiodarone, flecainide, ibutilide, or propafenone to facilitate electrical cardioversion.^{19,23,27–30}

Contemporary data suggest that pre-treatment is only used in a small number of patients undergoing cardioversion. In the X-VeRT trial (an international RCT of two oral anticoagulant strategies in 1504 AF patients undergoing elective cardioversion), fewer than 30% of participants were administered amiodarone, Class I, or III AADs before electrical cardioversion.³

This NMA demonstrated high certainty of evidence for pre-treating patients with amiodarone and Class III AADs before an electrical cardioversion to more than double the odds of the acute restoration of sinus rhythm. It has also shown with high certainty that amiodarone is the optimal AAD regimen for post-cardioversion maintenance of sinus rhythm. These results expand on the recommendations of major American, Canadian, and European guidelines and should lead to broader recommendations for pre-treatment in all patients undergoing elective electrical cardioversion of AF or specific recommendations for Class III AADs or amiodarone for acute restoration and amiodarone for the long-term maintenance of sinus rhythm.

Based on the absolute conversion rate of 75% for acute restoration in the no treatment or rate control arm in our study, pre-treatment with amiodarone may increase the restoration of sinus rhythm to 89%. Based on an absolute rate of 29% in the no treatment or rate control arm in this study, the long-term maintenance of sinus rhythm would have increased to 69% with pre- and post-treatment using amiodarone. Application of the evidence synthesized in this review may lead to improved outcomes for patients with AF by reducing healthcare resource utilization (e.g. repeat electrical cardioversion, unplanned visits), limiting the proportion of symptomatic patients abandoning a rhythm control strategy and decreasing the symptomatic burden during the waiting period for patients pursuing AF ablation. Scientific societies should review the scope and the strength of their recommendations considering these results. Meanwhile, clinicians may consider a broader and more consistent use of AAD pre-treatment before electrical cardioversion of AF.

Strengths

This NMA has several strengths. We performed a comprehensive search with high sensitivity and applied rigorous rule-based methods for data collection and assessment. We assessed the risk of bias for included studies and evaluated the certainty of evidence for outcomes of interest in accordance with GRADE methodology for NMA.

Limitations

To strengthen our network framework, we grouped Classes of AADs together which may have introduced heterogeneity to the network. We only included AADs that were currently available and approved for use in Canada or the United States. Excluded AADs included AZD7009, AZD1305, and bepridil. In addition, we were unable to classify the risk of selection bias for 9 studies due to inadequate reporting in published manuscripts. Finally, given the limited reporting of safety data in our included studies, we did not capture the data for this outcome. The adverse effects of AADs are well known and better addressed by studies with increased scope and the primary intent of answering that clinical question.

Conclusions

Pre-treatment with amiodarone or Class III AADs improves the acute restoration of sinus rhythm in patients with AF undergoing elective electrical cardioversion. Amiodarone is likely superior to other Class III and Ic agents for post-cardioversion maintenance of sinus rhythm.

Supplementary material

Supplementary material is available at Europace online.

Acknowledgements

We would like to thank Laura Banfield for refining our search strategy. We would also like to acknowledge Serena Sibilio, Cathevine Yang, and Alexandra Sibiga for their translation of Italian, Chinese, and Polish. The authors (W.F.M. and K.J.U.) are members of the Cardiac Arrhythmia Network of Canada (CANet) HQP Association for Trainees (CHAT).

Funding

This work was supported by a Mach-Gaensslen Medical Summer Student Research Grant (2017), McMaster University Department of Medicine Medical Student Research Award (2017), McMaster Medical Student Research Excellence Scholarship (2018), and Heart and Stroke Foundation Ontario Evelyn McGloin Summer Medical Student Scholarship (2018). Emilie Belley-Côté is supported by the E.J. Moran Campbell McMaster Internal Career Award and by a Heart and Stroke Foundation National New Investigator award. R.P.W. holds the Canada Research Chair in Cardiovascular Surgery.

Data Availability

The data underlying this article are available in the article and in its online supplementary material.

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