Mechanism

Endpoint	TE [95% CI]	p val	I2	n	k
death or hospitalization for cardiac causes	no data
cardiovascular events	no data
Cardiovascular death	no data
myocardial infarction (fatal and non fatal)	no data
stroke (fatal and non fatal)	no data
Atrial fibrillation recurrence	0.79 [0.64 0.99]	p=0.04	0	2078	8	Benditt, Singh, Bellandi (sotalol vs placebo), Carunchio (sotalol vs placebo), Kochiadakis b (sotalol vs placebo), PAFAC (sotalol vs placebo), SAFE-T (sotalol vs placebo), SOPAT (sotalol vs placebo),
Cardiac nonarrhythmic death	no data
Cardiac arrhythmic death	no data
Vascular noncardiac death	no data
hospitalization for AF	no data
hospitalisation for heart failure	no data
Pro-arrhythmia	2.06 [1.05 4.04]	p=0.04	0	2078	8	Benditt, Singh, Bellandi (sotalol vs placebo), Carunchio (sotalol vs placebo), Kochiadakis b (sotalol vs placebo), PAFAC (sotalol vs placebo), SAFE-T (sotalol vs placebo), SOPAT (sotalol vs placebo),
All cause death	1.73 [0.76 3.90]	p=1.00	0	2078	8	Benditt, Singh, Bellandi (sotalol vs placebo), Carunchio (sotalol vs placebo), Kochiadakis b (sotalol vs placebo), PAFAC (sotalol vs placebo), SAFE-T (sotalol vs placebo), SOPAT (sotalol vs placebo),
non cardiovascular death	no data
Adverse events leading to treatment discontinuation	1.10 [0.80 1.51]	p=1.00	0	1685	7	Benditt, Singh, Bellandi (sotalol vs placebo), Carunchio (sotalol vs placebo), Kochiadakis b (sotalol vs placebo), PAFAC (sotalol vs placebo), SOPAT (sotalol vs placebo),

Trial	Studied treatment	Control	Patients
Benditt, 1999	Sotalol various doses (80, 120, 160 mg/d) after cardioversion	placebo	patients with AF or AFl documented in the last 3 months
Singh, 1991	Sotalol 80 - 320 mg/d	placebo	Persistent AF or AFl lasting 2 weeks to 1 year
Bellandi (sotalol vs placebo), 2001	sotalol 240 mg/d	placebo	patients with paroxysmal recurrent or persistent AF
Carunchio (sotalol vs placebo), 1995	sotalol 240 mg/d ,	placebo	patients with recurrent AF with > 3 episodes in previous 1 year
Kochiadakis (sotalol vs placebo), 2000	sotalol 320 mg/d	placebo	Any documented symptomatic previous or persistent AF
Kochiadakis b (sotalol vs placebo), 2004	sotalol 300 mg/d	placebo	Any documented symptomatic previous or persistent AF
PAFAC (sotalol vs placebo), 2004	sotalol 320 mg/d ,	placebo	Persistent AF lasting > 7 daysil
SAFE-T (sotalol vs placebo), 2005	sotalol 320 mg/d	placebo	Persistent AF lasting 3 days to 1 year
SOPAT (sotalol vs placebo), 2004	sotalol 320 mg/d ,	placebo	Paroxysmal AF documented in the last 1 month@4

Sotalol

all NS

Sotalol

all NS

Sotalol

all NS

Dronedarone

atrial fibrillation, in maintaining sinus rhythm after cardioversion

death or hospitalization for cardiac causes by 15% suggested

cardiovascular events by 16% suggested

Cardiovascular death by 29% suggested

stroke (fatal and non fatal) by 135% suggested

Atrial fibrillation recurrence by 29% suggested

Cardiac arrhythmic death by 45% suggested

hospitalization for AF by 34% suggested

Adverse events leading to treatment discontinuation by 55% suggested

Endpoint	TE [95% CI]	p val	n	k
death or hospitalization for cardiac causes	0.85 [0.77 0.94]	p=0.04	9014	4	EURIDIS, ADONIS, ATHENA, PALLAS,
cardiovascular events	0.84 [0.75 0.95]	p=0.04	7777	2	ATHENA, PALLAS,
Cardiovascular death	0.71 [0.51 0.98]	p=0.04	4628	1	ATHENA,
myocardial infarction (fatal and non fatal)	1.00 [0.20 4.95]	p=1.00	3149	1	PALLAS,
stroke (fatal and non fatal)	2.35 [1.04 5.34]	p=0.04	4386	2	EURIDIS ADONIS (pooled analysis), PALLAS,
Atrial fibrillation recurrence	0.71 [0.64 0.79]	p=0.04	6064	4	EURIDIS, ADONIS, DAFNE, ATHENA,
Cardiac nonarrhythmic death	0.96 [0.49 1.86]	p=1.00	4628	1	ATHENA,
Cardiac arrhythmic death	0.55 [0.34 0.89]	p=0.04	4628	1	ATHENA,
Vascular noncardiac death	0.84 [0.46 1.53]	p=1.00	4628	1	ATHENA,
hospitalization for AF	0.66 [0.57 0.77]	p=0.04	4628	1	ATHENA,
hospitalisation for heart failure	0.99 [0.78 1.26]	p=1.00	7777	2	ATHENA, PALLAS,
Pro-arrhythmia	0.32 [0.01 16.24]	p=1.00	199	1	DAFNE,
All cause death	0.92 [0.72 1.17]	p=1.00	9213	4	DAFNE, EURIDIS ADONIS (pooled analysis), ATHENA, PALLAS,
non cardiovascular death	1.09 [0.74 1.62]	p=1.00	4628	1	ATHENA,
Adverse events leading to treatment discontinuation	1.55 [1.30 1.85]	p=0.04	6064	3	DAFNE, EURIDIS ADONIS (pooled analysis), ATHENA,

Trial	Studied treatment	Control	Patients
EURIDIS, 2007	dronedarone 400 mg twice daily	placebo	patients with at least one episode of atrial fibrillation in the preceding 3 months, and in sinus rhythm for at least 1 hour before randomization
ADONIS, 2007	dronedarone 400 mg twice daily	placebo	patients with at least one episode of atrial fibrillation in the preceding 3 months, and in sinus rhythm for at least 1 hour before randomization
DAFNE, 2003	Dronedarone various doses (800, 1200, 1600 mg/d)	placebo	patients with Persistent AF
EURIDIS ADONIS (pooled analysis), 2009	Dronedarone 800 mg/d	placebo	AF documented in the previous 3 months
ATHENA, 2009	dronedarone 400 mg twice a day	placebo	patients (>70y) with paroxysmal or persistent atrial fibrillation and additional risk factors for death
PALLAS, 2011	Dronedarone	placebo	patients with permanent atrial fibrillation and additional risk factors

Dronedarone

Adverse events leading to treatment discontinuation by 52% suggested

Dronedarone

atrial fibrillation, in rate control

all NS

Dronedarone

atrial fibrillation, in prevention of cardiovascular events

death or hospitalization for cardiac causes by 45% suggested

cardiovascular events by 128% suggested

stroke (fatal and non fatal) by 142% suggested

hospitalisation for heart failure by 126% suggested

Dronedarone

heart failure, in all type of heart failure

All cause death by 113% suggested

Magnesium

acute myocardial infarction, in all type of patients

Bradycardia by 642% adverse event

Ventricular fibrillation by 11% suggested

II-III atrio ventricular block by 7% suggested

Cardiogenic shock by 10% suggested

severe arrhythmia by 61% suggested

Heart failure by 7% suggested

Hypotension by 11% suggested

Magnesium

Bradycardia by 47% adverse event

Cardiogenic shock by 47% suggested

All cause death by 12% suggested

Endpoint	TE [95% CI]	p val	I2	n	k
Ventricular fibrillation	0.81 [0.39 1.72]	p=1.00	0	936	8	Abraham, Bhargava, Ceremuzynski, Chen, Feldstedt, Gyamlani, Morton, Nakashima,
II-III atrio ventricular block	0.97 [0.88 1.08]	p=1.00	0	9924	13	MAGIC, Feldstedt, Gyamlani, Morton, Nakashima, Parikka, Rasmussen, Santoro, Shechter, Shechter, Shechter, Urek, Woods,
Cardiogenic shock	0.53 [0.30 0.93]	p=0.04	0	1105	10	Abraham, Bhargava, Ceremuzynski, Gyamlani, Nakashima, Rasmussen, Shechter, Shechter, Shechter, Singh,
severe arrhythmia	0.85 [0.71 1.03]	p=1.00	0	7126	9	MAGIC, Chen, Rasmussen, Shechter, Shechter, Shechter, Singh, Smith, Urek,
Heart failure	0.97 [0.88 1.09]	p=1.00	0	9714	10	MAGIC, Feldstedt, Gyamlani, Morton, Nakashima, Parikka, Rasmussen, Santoro, Shechter, Woods,
Hypotension	1.07 [0.76 1.51]	p=1.00	0	2618	4	Abraham, Morton, Singh, Woods,
All cause death	0.88 [0.78 0.99]	p=0.04	0	11020	19	Abraham, MAGIC, Bhargava, Ceremuzynski, Feldstedt, Gyamlani, Morton, Nakashima, Raghu, Rasmussen, Santoro, Shechter, Shechter, Shechter, Singh, Smith, Thogersen, Urek, Woods,
Bradycardia	1.47 [1.12 1.93]	p=0.04	0	3218	7	Abraham, Bhargava, Gyamlani, Raghu, Rasmussen, Santoro, Woods,
Flushing	no data

Trial	Studied treatment	Control	Patients
Abraham, 1987	2.4g of magnesium sulfate in 50 ml of 5% glucose solution intravenously over a 20 minutes period for 3 days	50 ml of 5% glucose solution alone, imag	patients with AMI
MAGIC, 2000	2 g intravenous bolus of MgSO4 over 15 minutes, followed by a 17 g infusion of MgSO4 over 24 h	matched intravenous bolus and 24 h infusion of sterile waterndºã	AMi patients within 6 h of onset of symptomsm
Bhargava, 1995	8 mmol magnesium sulphate over 5 min followed by 65 mmol over 24-h infusion	isotonic saline infusion	proven AMI patients with chest pain of 1-6h
Ceremuzynski, 1989	8 g MgSO4 in 500 mL 15% glucose for 24 h intravenouslypj	conventional treatmenton	patients with AMI within 12 h from onset of symptomslypj
Chen, 1991	MgSO4 2g/day for 3 daysn	5% glucose	patients with AMI
Feldstedt, 1991	continuous infusion of 80 mmol magnesium chloride in 1000 mL dextrose˜K	matching placebo	patients, aged 75 y or less, with suspected AMI less than 8 h+—²
Gyamlani, 2000	magnesium 12g (50 mmol) in the first 24h, 3g (12 mmol) in the second 24h used within 2h after admission and within 30 minutes of thrombolytic therapy™	equal volume of isotonic glucose	patients with proven AMI
Ising, 1990	81 mval/daymagnesium sulphate infusion 13+/-9h after the onset of severe pain for 3 days	80 mval/day NaCl infusion for 3 daysimag	patients with AMI
Morton, 1984	36 h intravenous infusion of magnesium sulphate (0.75 mEq/kg/body weight/12 h).	saline solution infusion	patients with AMI within 8 h of onsetmag
Nakashima, 2004	bolus injection of 8 mmol of magnesium followed by an infusion of 24 mmol over 24 h	equivalent amount of normal saline, imag	patients with successful PCI weree, imag
Parikka, 1990	8mmol MgSO4 in 10 min, 62 mmol in 24hmag	NaCl ¯B	patients with < 12 h from onset of chest pain AMImage/pj
Raghu, 1999	18 g (75.6 mmol) of Mg sulphate over 24 h started immediately after completion of thrombolytic therapy	equivalent amount of salinexbitm	confirmed AMI < 6 h from the onset of symptomsce
Rasmussen, 1986	50 mmol MgCl2 during the first 24 h, 12 mmol during the second 24 h	isotonic glucose	patients with suspected AMIxbitm
Santoro, 2000	MgSO4 7 g (28 mmol) with 5 hon	matching saline solution
Shechter, 1990	magnesium 22 g (91.6 mmol) within 48 h (67 mmol within first 24 h).	isotonic glucose.	patients with admission diagnosis of AMI
Shechter, 1991	22 g (91.6 mmol) within 48 h (67 mmol within first 24 h).	isotonic glucose.	patients with documented AMIbitm
Shechter, 1995	magnesium 22 g (91.6mmol) within 48 h (67mmol within first 24 h)pj	isotonic glucose	suspected with AMI and considered unsuitable candidates for thrombolysis
Singh, 1990	5 g (8.12 mmol) of MgSO4 daily for 4 daysptomsce	2% dextrose solution for 3 daysm	patients suspected with AMI within 8-12h of the onset of MI
Smith, 1986	65 mmol MgSO4 given over 24 h	Saline	patients with suspected AMI h.tm
Thogersen, 1995	magensium 50 mmol within 24 h	isotonic NaCl.	patients with suspected AMI
Urek, 1996	17 g MgSO4 with first 24 h.xbitm	saline.	patients with documented AMIbitm
Woods, 1992	magnesium 8 mmol over 5 min, 65 mmol over 24h imag	physiological saline hon	patients with suspected AMI in the preceding 24h

antiarrythmic drugs