atrial fibrillation

Description Results NMA

Atrial fibrillation recurrence 0.54 [0.41; 0.69]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects 4.98 [0.65; 38.29]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.32 [0.17; 0.60]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects ∞ [NaN; ∞]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.53 [0.39; 0.73]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects ∞ [NaN; ∞]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.58 [0.50; 0.66]

all cause mortality 2.14 [0.62; 7.39]

Pro-arrhythmia 1.48 [0.30; 7.25]

Amiodarone 200 mg/d (n=61)

vs.

placebo (n=38)

double blind

Parallel groups

Sample size: 61/38

Primary endpoint:

FU duration: 12 months

Amiodarone 200 mg/d (n=35)

vs.

placebo (n=15)

double blind

Parallel groups

Sample size: 35/15

Primary endpoint:

FU duration: 16 months

Amiodarone 200 mg/d (n=65)

vs.

placebo (n=60)

single

Parallel groups

Sample size: 65/60

Primary endpoint:

FU duration: 24 months

Amiodarone 300 mg/d (n=267)

vs.

placebo (n=137)

double blind

Parallel groups

Sample size: 267/137

Primary endpoint: recurrence of atrial fibrillation

FU duration: 12 months

all cause mortality 0.42 [0.21; 0.83]

Withdrawals due to adverse effects 0.33 [0.21; 0.53]

Pro-arrhythmia 0.20 [0.08; 0.51]

Atrial fibrillation recurrence 0.66 [0.55; 0.80]

Cardiac arrhythmic death 0.63 [0.19; 2.08]

Amiodarone 200 mg/d , (n=106)

vs.

class I drugs (n=116)

open

Parallel groups

Sample size: 106/116

Primary endpoint: success

FU duration: 12 months, and 3.8y

Amiodarone 200 mg/d , , sotalol (n=-9)

vs.

class I drugs (n=-9)

open

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration: 12 months, and 3.8y

Atrial fibrillation recurrence 0.55 [0.35; 0.85]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects 0.35 [0.10; 1.18]

Atrial fibrillation recurrence 0.40 [0.18; 0.88]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects 0.93 [0.06; 14.10]

Pro-arrhythmia 0.93 [0.06; 14.10]

Amiodarone 200 mg/d (n=35)

vs.

disopyramide 500 mg/d (n=41)

open

Parallel groups

Sample size: 35/41

Primary endpoint:

FU duration: 14 months

Amiodarone 400 mg/d (n=28)

vs.

Quinidine 1,2 g/d (n=26)

open

Parallel groups

Sample size: 28/26

Primary endpoint:

FU duration: 6 months

Withdrawals due to adverse effects 8.74 [2.09; 36.46]

all cause mortality NaN [NaN; NaN]

Pro-arrhythmia 1.03 [0.15; 7.10]

Atrial fibrillation recurrence 0.64 [0.41; 1.01]

Amiodarone 200 mg/d (n=72)

vs.

propafenone 450 mg/d (n=74)

single

Parallel groups

Sample size: 72/74

Primary endpoint:

FU duration: 24 months

Atrial fibrillation recurrence 0.68 [0.54; 0.86]

all cause mortality 0.60 [0.33; 1.08]

Withdrawals due to adverse effects 0.83 [0.47; 1.47]

Pro-arrhythmia 0.49 [0.17; 1.42]

Cardiac arrhythmic death 0.95 [0.28; 3.22]

Amiodarone 200 mg/d (n=131)

vs.

Sotalol 240 mg/d (n=125)

open

Parallel groups

Sample size: 131/125

Primary endpoint:

FU duration: mean 3.8y

Amiodarone 200 mg/d , Amiodarone 200 mg/d (n=65)

vs.

(n=61)

single

Parallel groups

Sample size: 65/61

Primary endpoint:

FU duration: 24 months

Amiodarone 300 mg/d , Amiodarone 300 mg/d (n=267)

vs.

(n=261)

double blind

Parallel groups

Sample size: 267/261

Primary endpoint:

FU duration: 12 months

Withdrawals due to adverse effects 2.30 [1.20; 4.39]

all cause mortality 1.23 [0.38; 3.99]

Pro-arrhythmia 6.04 [0.78; 46.62]

Azimilide various doses (35 to 125 mg/d) after pharmacological or electrical cardioversion (n=891)

vs.

placebo (n=489)

double blind

Parallel groups

Sample size: 891/489

Primary endpoint:

FU duration: 6 months

all cause mortality ∞ [NaN; ∞]

Withdrawals due to adverse effects 3.50 [0.77; 15.96]

Pro-arrhythmia NaN [NaN; NaN]

Atrial fibrillation recurrence 0.75 [0.54; 1.05]

all cause mortality NaN [NaN; NaN]

Pro-arrhythmia NaN [NaN; NaN]

Atrial fibrillation recurrence 0.81 [0.53; 1.24]

Disopyramide 500 mg/d (n=46)

vs.

palcebo (n=46)

open

Parallel groups

Sample size: 46/46

Primary endpoint:

FU duration: 12 months

Disopyramide 450 mg/d , (n=29)

vs.

placebo (n=25)

double blind

Parallel groups

Sample size: 29/25

Primary endpoint:

FU duration: 6 months

Disopyramide 450 mg/d , , (n=29)

vs.

placebo (n=28)

double blind

Parallel groups

Sample size: 29/28

Primary endpoint:

FU duration: 6 months

all cause mortality ∞ [NaN; ∞]

Withdrawals due to adverse effects 0.40 [0.14; 1.19]

Pro-arrhythmia 0.81 [0.05; 12.26]

Atrial fibrillation recurrence 0.73 [0.37; 1.44]

Disopyramide 750 mg/d (n=31)

vs.

propafenone 900 mg/d (n=25)

double blind

Parallel groups

Sample size: 31/25

Primary endpoint:

FU duration: 6 months

Atrial fibrillation recurrence 0.62 [0.54; 0.70]

all cause mortality 0.99 [0.77; 1.29]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.85 [0.72; 1.00]

all cause mortality 0.75 [0.19; 2.90]

Withdrawals due to adverse effects 1.68 [0.37; 7.59]

Pro-arrhythmia 4.48 [0.59; 33.83]

Dofetilide 500 mcg/d5 (n=249)

vs.

placebo (n=257)

double blind

Parallel groups

Sample size: 249/257

Primary endpoint:

FU duration: 24 months

Dofetilide various doses (250, 500, 1000 mcg/d) (n=182)

vs.

placebo (n=68)

double blind

Parallel groups

Sample size: 182/68

Primary endpoint:

FU duration: 12 months

Atrial fibrillation recurrence 0.78 [0.64; 0.95]

Death, unplanned CV hospitalization 0.66 [0.47; 0.93]

Atrial fibrillation recurrence 0.73 [0.60; 0.89]

Death, unplanned CV hospitalization 0.80 [0.56; 1.14]

Atrial fibrillation recurrence 0.86 [0.75; 0.98]

all cause mortality ∞ [NaN; ∞]

Withdrawals due to adverse effects ∞ [NaN; ∞]

Pro-arrhythmia NaN [NaN; NaN]

all cause mortality 1.32 [0.35; 4.94]

Stroke 1.98 [0.22; 17.62]

Withdrawals due to adverse effects 1.36 [0.91; 2.05]

cardiovascular death 0.71 [0.52; 0.97]

Cardiovascular events 0.81 [0.75; 0.88]

Cardiac arrhythmic death 0.55 [0.34; 0.88]

hospitalization for AF 0.66 [0.59; 0.75]

Atrial fibrillation recurrence 0.66 [0.59; 0.75]

Death, unplanned CV hospitalization 0.81 [0.75; 0.88]

Withdrawals due to adverse effects 1.57 [1.32; 1.87]

all cause mortality 0.84 [0.66; 1.07]

HF hospitalization 0.86 [0.67; 1.10]

non CV death 1.09 [0.74; 1.61]

Vascular noncardiac death 0.84 [0.47; 1.52]

Cardiac nonarrhythmic death 0.96 [0.49; 1.85]

all cause mortality ∞ [NaN; ∞]

Withdrawals due to adverse effects 1.51 [0.68; 3.35]

Stroke 2.42 [1.01; 5.82]

HF hospitalization 2.26 [1.24; 4.13]

Cardiovascular events 2.28 [1.22; 4.25]

Death, unplanned CV hospitalization 1.45 [1.10; 1.91]

all cause mortality 2.28 [0.94; 5.52]

MI 1.00 [0.20; 4.93]

dronedarone 400 mg twice daily (n=411)

vs.

placebo (n=201)

double blind

Parallel groups

Sample size: 411/201

Primary endpoint: recurrence of atrial fibrillation

FU duration: 12 months

dronedarone 400 mg twice daily (n=417)

vs.

placebo (n=208)

double blind

Parallel groups

Sample size: 417/208

Primary endpoint: recurrence of atrial fibrillation

FU duration: 12 months

Dronedarone various doses (800, 1200, 1600 mg/d) (n=151)

vs.

placebo (n=48)

double blind

Parallel groups

Sample size: 151/48

Primary endpoint:

FU duration:

Dronedarone 800 mg/d (n=828)

vs.

placebo (n=409)

double blind

Parallel groups

Sample size: 828/409

Primary endpoint: First Recurrence of Atrial Fibrillation or flutter

FU duration: 12 months

dronedarone 400 mg twice a day (n=2301)

vs.

placebo (n=2327)

double blind

Parallel groups

Sample size: 2301/2327

Primary endpoint: first hospitalization due to cardiovascular events or death

FU duration: 21.5 months

dronedarone 400 mg twice daily (n=85)

vs.

placebo (n=89)

double blind

Parallel groups

Sample size: 85/89

Primary endpoint: ventricular rate

FU duration: 6 months

Dronedarone (n=1577)

vs.

placebo (n=1572)

double-blind

Parallel groups

Sample size: 1577/1572

Primary endpoint: major cardiovascular events

FU duration: 3 years

Withdrawals due to adverse effects 0.48 [0.25; 0.90]

Atrial fibrillation recurrence 1.34 [1.17; 1.53]

all cause mortality 0.41 [0.08; 2.09]

Dronedarone (400mg BID) (n=249)

vs.

Amiodarone (600mg daily for 28 days, then 200mg daily thereafter) (n=255)

double blind

Parallel groups

Sample size: 249/255

Primary endpoint: treatment failure

FU duration: 6 months

Atrial fibrillation recurrence 0.41 [0.20; 0.83]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects NaN [NaN; NaN]

Pro-arrhythmia ∞ [NaN; ∞]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects ∞ [NaN; ∞]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.81 [0.55; 1.20]

Flecainide 200 mg/d (n=20)

vs.

placebo (n=26)

open

Parallel groups

Sample size: 20/26

Primary endpoint:

FU duration: 12 months

Flecainide 200-300 mg/d (n=36)

vs.

no treatment (n=37)

open

Parallel groups

Sample size: 36/37

Primary endpoint:

FU duration: 12 months

Withdrawals due to adverse effects 1.66 [1.04; 2.65]

all cause mortality NaN [NaN; NaN]

Pro-arrhythmia 1.49 [0.59; 3.78]

Atrial fibrillation recurrence 1.04 [0.91; 1.19]

Flecainide 200-300 mg/d (n=117)

vs.

Quinidine 1-1,5 g/d (n=122)

double blind

Parallel groups

Sample size: 117/122

Primary endpoint:

FU duration: 12 months

Withdrawals due to adverse effects 0.23 [0.05; 1.00]

all cause mortality 0.00 [0.00; NaN]

Pro-arrhythmia 0.00 [0.00; NaN]

Atrial fibrillation recurrence 0.75 [0.48; 1.16]

Flecainide 100-200mg/d (n=48)

vs.

Propafenone 600 mg/d (n=49)

open

Parallel groups

Sample size: 48/49

Primary endpoint:

FU duration: 12 months

Atrial fibrillation recurrence 0.46 [0.24; 0.88]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects NaN [NaN; NaN]

Pro-arrhythmia 1.00 [0.07; 14.55]

flecainide 200-300 mg/d (+ digoxine) (n=15)

vs.

(n=15)

open

Parallel groups

Sample size: 15/15

Primary endpoint:

FU duration: 12 months

Withdrawals due to adverse effects 3.33 [1.37; 8.12]

all cause mortality ∞ [NaN; ∞]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.91 [0.79; 1.04]

Metoprolol 100 mg/d (n=197)

vs.

placebo (n=197)

double blnd

Parallel groups

Sample size: 197/197

Primary endpoint:

FU duration: 6 months

Atrial fibrillation recurrence 0.65 [0.50; 0.85]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects 2.71 [0.76; 9.69]

Pro-arrhythmia NaN [NaN; NaN]

Atrial fibrillation recurrence 0.69 [0.49; 0.97]

all cause mortality 0.00 [0.00; NaN]

Withdrawals due to adverse effects 3.59 [0.41; 31.07]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.58 [0.44; 0.78]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects ∞ [NaN; ∞]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.71 [0.63; 0.79]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects 1.29 [0.79; 2.11]

Pro-arrhythmia NaN [NaN; NaN]

all cause mortality 0.00 [0.00; NaN]

Withdrawals due to adverse effects 1.14 [0.25; 5.12]

Pro-arrhythmia 0.49 [0.09; 2.75]

Atrial fibrillation recurrence 0.71 [0.50; 1.01]

Propafenone 900 mg/d/d after pharmacological or electrical cardioversion (n=102)

vs.

placebo (n=92)

double blind

Parallel groups

Sample size: 102/92

Primary endpoint:

FU duration: 12 months

Propafenone 450 mg/d (n=58)

vs.

placebo (n=52)

single

Parallel groups

Sample size: 58/52

Primary endpoint:

FU duration: 15 months

Propafenone 450 mg/d (n=86)

vs.

placebo (n=83)

single

Parallel groups

Sample size: 86/83

Primary endpoint:

FU duration: 24 months

Propafenone at various doses (450, 650, 850 mg/d) (n=397)

vs.

placebo. (n=126)

double blind

Parallel groups

Sample size: 397/126

Primary endpoint:

FU duration: 9 months

Propafenone 450 mg/d (n=77)

vs.

placebo (n=25)

double blind

Parallel groups

Sample size: 77/25

Primary endpoint:

FU duration: 6 months

Withdrawals due to adverse effects 2.39 [1.20; 4.77]

all cause mortality 0.00 [0.00; NaN]

Pro-arrhythmia 1.04 [0.15; 7.24]

Atrial fibrillation recurrence 1.12 [0.87; 1.44]

Propafenone 900 mg/d (n=98)

vs.

Quinidine 1 g/d mg/d (n=102)

open

Parallel groups

Sample size: 98/102

Primary endpoint:

FU duration: 12 months

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects 1.18 [0.50; 2.78]

Pro-arrhythmia 2.12 [0.20; 23.05]

Atrial fibrillation recurrence 1.06 [0.70; 1.62]

propafenone 520 mg/dt (n=97)

vs.

Flecainide 200 mg/d (n=103)

open

Parallel groups

Sample size: 97/103

Primary endpoint:

FU duration: 12 months

all cause mortality ∞ [NaN; ∞]

Withdrawals due to adverse effects 1.50 [0.45; 4.99]

Pro-arrhythmia 1.50 [0.58; 3.90]

Atrial fibrillation recurrence 0.91 [0.69; 1.20]

Propafenone 675 mg/d (n=50)

vs.

Sotalol 320 mg/d (n=50)

open

Parallel groups

Sample size: 50/50

Primary endpoint:

FU duration: 12 months

all cause mortality ∞ [NaN; ∞]

Withdrawals due to adverse effects ∞ [NaN; ∞]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.74 [0.48; 1.15]

all cause mortality ∞ [NaN; ∞]

Withdrawals due to adverse effects ∞ [NaN; ∞]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.84 [0.55; 1.28]

Atrial fibrillation recurrence 0.78 [0.69; 0.88]

all cause mortality 1.05 [0.23; 4.78]

Withdrawals due to adverse effects 1.10 [0.72; 1.68]

Pro-arrhythmia 1.98 [0.47; 8.43]

Withdrawals due to adverse effects 0.74 [0.55; 1.00]

Atrial fibrillation recurrence 0.89 [0.82; 0.96]

all cause mortality ∞ [NaN; ∞]

Pro-arrhythmia 1.29 [0.35; 4.83]

Atrial fibrillation recurrence 0.73 [0.58; 0.92]

Withdrawals due to adverse effects 5.68 [1.78; 18.14]

all cause mortality 2.05 [0.42; 9.86]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.79 [0.64; 0.97]

all cause mortality ∞ [NaN; ∞]

Withdrawals due to adverse effects 1.46 [0.67; 3.16]

Pro-arrhythmia ∞ [NaN; ∞]

(n=-9)

vs.

(n=-9)

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration:

quinidine 1.4 g/d (n=-9)

vs.

placebo (n=25)

double blind

Parallel groups

Sample size: -9/25

Primary endpoint:

FU duration: 6 months

Quinidine 0,480 g/d (+ verapamil (n=377)

vs.

placebo (n=88)

double blind

Parallel groups

Sample size: 377/88

Primary endpoint:

FU duration: 12 months

Quinidine 0,320 or 0,480 g/d (+ verapamil) (n=518)

vs.

placebo (n=251)

double blind

Parallel groups

Sample size: 518/251

Primary endpoint:

FU duration: 12 months

Quinidine 1.2 - 1.8 g/d (n=110)

vs.

no treatment (n=75)

open

Parallel groups

Sample size: 110/75

Primary endpoint:

FU duration: 12 months

Quinidine 1.2 g/d (n=32)

vs.

placebo (n=42)

double blind

Parallel groups

Sample size: 32/42

Primary endpoint:

FU duration: 12 months

quinidine 1.4 g/d , quinidine 1.4 g/d (n=28)

vs.

(n=29)

double blind

Parallel groups

Sample size: 28/29

Primary endpoint:

FU duration: 6 months

Quinidine 1 g/d (+ digoxine) , Quinidine 1 g/d (+ digoxine) (n=15)

vs.

(n=15)

open

Parallel groups

Sample size: 15/15

Primary endpoint:

FU duration: 12 months

Withdrawals due to adverse effects 10.00 [1.38; 72.39]

all cause mortality NaN [NaN; NaN]

Pro-arrhythmia 3.00 [0.33; 26.92]

Atrial fibrillation recurrence 0.58 [0.28; 1.23]

Withdrawals due to adverse effects 2.31 [1.19; 4.47]

all cause mortality 1.15 [0.07; 18.15]

Pro-arrhythmia 1.15 [0.07; 18.15]

Atrial fibrillation recurrence 1.13 [0.87; 1.47]

all cause mortality ∞ [NaN; ∞]

Withdrawals due to adverse effects 2.33 [0.65; 8.40]

Pro-arrhythmia 0.50 [0.05; 5.30]

Atrial fibrillation recurrence 0.71 [0.43; 1.18]

all cause mortality 0.00 [0.00; NaN]

Withdrawals due to adverse effects 1.32 [0.54; 3.23]

Pro-arrhythmia 0.61 [0.11; 3.54]

Atrial fibrillation recurrence 1.15 [0.72; 1.84]

Quinidine 1 g/d (n=25)

vs.

sotalol 240-320 mg/dt (n=25)

open

Parallel groups

Sample size: 25/25

Primary endpoint:

FU duration: 6 months

Quinidine 1,2 g/d (n=85)

vs.

Sotalol 160-320 mg/dt (n=98)

open

Parallel groups

Sample size: 85/98

Primary endpoint:

FU duration: 6 months

Quinidine 1 g/d (n=41)

vs.

Sotalol 240-400 mg/dt (n=41)

open

Parallel groups

Sample size: 41/41

Primary endpoint:

FU duration: 12 months

Quinidine 700 mg/d (n=63)

vs.

sotalol 240 mg/d (n=58)

open

Parallel groups

Sample size: 63/58

Primary endpoint:

FU duration: 6 months

Quinidine 0,480 g/d (+ verapamil , Quinidine 0,480 g/d (+ verapamil (n=377)

vs.

(n=383)

double blind

Parallel groups

Sample size: 377/383

Primary endpoint:

FU duration: 12 months

Quinidine 0,320 or 0,480 g/d (+ verapamil) , Quinidine 0,320 or 0,480 g/d (+ verapamil) (n=518)

vs.

(n=264)

double blind

Parallel groups

Sample size: 518/264

Primary endpoint:

FU duration: 12 months

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects ∞ [NaN; ∞]

Pro-arrhythmia 2.00 [0.20; 19.78]

Atrial fibrillation recurrence 0.77 [0.51; 1.16]

Quinidine 1 g/d (+ digoxine) (n=15)

vs.

digoxine alone (n=15)

open

Parallel groups

Sample size: 15/15

Primary endpoint:

FU duration: 12 months

Withdrawals due to adverse effects 9.38 [1.29; 67.87]

all cause mortality NaN [NaN; NaN]

Pro-arrhythmia 1.38 [0.40; 4.78]

Atrial fibrillation recurrence 0.98 [0.84; 1.14]

Atrial fibrillation recurrence 0.79 [0.64; 0.97]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects ∞ [NaN; ∞]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.57 [0.43; 0.76]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects 2.03 [0.54; 7.61]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.55 [0.30; 0.98]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects NaN [NaN; NaN]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.72 [0.56; 0.93]

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects ∞ [NaN; ∞]

Pro-arrhythmia ∞ [NaN; ∞]

Atrial fibrillation recurrence 0.80 [0.71; 0.90]

all cause mortality 1.49 [0.34; 6.50]

Withdrawals due to adverse effects 1.10 [0.72; 1.68]

Pro-arrhythmia 2.30 [0.55; 9.65]

Atrial fibrillation recurrence 0.81 [0.73; 0.90]

all cause mortality 2.53 [0.75; 8.58]

Pro-arrhythmia 2.28 [0.50; 10.38]

all cause mortality ∞ [NaN; ∞]

Withdrawals due to adverse effects 0.88 [0.63; 1.23]

Pro-arrhythmia 0.63 [0.11; 3.76]

Atrial fibrillation recurrence 0.92 [0.84; 1.01]

Sotalol various doses (80, 120, 160 mg/d) after cardioversion (n=184)

vs.

placebo (n=69)

double blind

Parallel groups

Sample size: 184/69

Primary endpoint:

FU duration: 12 months

Sotalol 80 - 320 mg/d (n=24)

vs.

placebo (n=10)

double blind

Parallel groups

Sample size: 24/10

Primary endpoint:

FU duration: 6 months

sotalol 240 mg/d (n=106)

vs.

placebo (n=92)

double blind

Parallel groups

Sample size: 106/92

Primary endpoint:

FU duration: 12 months

sotalol 240 mg/d , (n=20)

vs.

placebo (n=26)

open

Parallel groups

Sample size: 20/26

Primary endpoint:

FU duration: 12 months

sotalol 320 mg/d (n=-9)

vs.

placebo (n=-9)

single

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration: 24 months

sotalol 300 mg/d (n=85)

vs.

placebo (n=83)

single

Parallel groups

Sample size: 85/83

Primary endpoint:

FU duration: 24 months

sotalol 320 mg/d , (n=383)

vs.

placebo (n=88)

double blind

Parallel groups

Sample size: 383/88

Primary endpoint:

FU duration: 12 months

sotalol 320 mg/d (n=261)

vs.

placebo (n=132)

double blind

Parallel groups

Sample size: 261/132

Primary endpoint:

FU duration: 12 months

sotalol 320 mg/d , (n=264)

vs.

placebo (n=251)

double blind

Parallel groups

Sample size: 264/251

Primary endpoint:

FU duration: 12 months

sotalol 240 mg/d , , sotalol 240 mg/d , (n=20)

vs.

(n=20)

open

Parallel groups

Sample size: 20/20

Primary endpoint:

FU duration: 12 months

sotalol 300 mg/d , , sotalol 300 mg/d , (n=85)

vs.

(n=86)

single

Parallel groups

Sample size: 85/86

Primary endpoint:

FU duration: 24 months

all cause mortality NaN [NaN; NaN]

Withdrawals due to adverse effects 1.33 [0.31; 5.72]

Pro-arrhythmia 1.33 [0.31; 5.72]

Atrial fibrillation recurrence 1.07 [0.74; 1.55]

Sotalol 160 mg/d (n=64)

vs.

bisoprolol 5 mg/d (n=64)

open

Parallel groups

Sample size: 64/64

Primary endpoint:

FU duration: 8 months

stroke*(all stroke or ischemic stroke) 0.91 [0.71; 1.18]

Non fatal TE event,bleedings and vascular death 0.89 [0.74; 1.09]

thromboembolic event*(TE event or ischemic stroke or systemic thromboembolic event) 0.82 [0.60; 1.11]

stroke,myocardial infarction,systemic arterial emboli or vascular death 2.66 [0.53; 13.33]

Non fatal TE event,bleedings and vascular death 2.66 [0.53; 13.33]

fatal bleeding 2.13 [0.20; 23.03]

thromboembolic event*(TE event or ischemic stroke or systemic thromboembolic event) 2.13 [0.20; 23.03]

aspirin 300 mg/d (n=404)

vs.

placebo (n=378)

There were 2 groups in the study: -patients eligible for anticoagulation(g1) who were randomly assigned to receive either open label oral anticoagulants or double blind treatment with aspirin or placebo -patients ineligible for anticoagulation (g2) who were randomised to double blind treatment with aspirin 300 mg or matching placebo.

Double blind

Parallel groups

Sample size: 404/378

Primary endpoint: death from vascular disease,stroke,myocardial infarction or sytemic embolism

FU duration: 2.3 years

fluidione standard dose (target INR: 2-2.6) + aspirin low dose 100 mg (n=76)

vs.

fluidione standard dose(target INR:2-2.6) + placebo (n=81)

Double blind

Parallel groups

Sample size: 76/81

Primary endpoint: stroke,myocardial infarction,systemic arterial emboli or vascular death

FU duration: 0.84 y

fatal stroke(ischemic+hemorrhagic) 0.72 [0.59; 0.88]

thrombo-embolic event (cerebral or systemic) 0.90 [0.83; 0.98]

ischemic stroke 0.69 [0.59; 0.81]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.89 [0.89; 0.89]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.73 [0.63; 0.84]

major bleeding 1.57 [1.29; 1.91]

all death 0.98 [0.90; 1.07]

vascular death 1.00 [0.91; 1.11]

haemorragic stroke(or intracerebral hemorrhage) 1.37 [0.79; 2.37]

fatal bleeding 1.56 [0.96; 2.52]

clopidogrel 75 mg daily + aspirin 75-100 mg daily (n=3772)

vs.

aspirin 75-100 mg daily alone (n=3782)

double blind

Parallel groups

Sample size: 3772/3782

Primary endpoint: stroke, MI, systemic embolus, or vascular death

FU duration: 3.7 y

non fatal TE events,bleedings and vascular death* 0.86 [0.35; 2.11]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 1.07 [0.22; 5.22]

coumarin low dose(target INR 1.1-1.6) (n=122)

vs.

coumarin standard dose(target INR 2.5-3.5) (n=131)

The PATAF trial includes 2 strata: -patients eligible for standard intensity coumarin:randomly assigned to standard anticoagulation(INR 2.5-3.5),very low intensity anticoagulation(INR 1.1-1.6) or aspirin(150mg/d). -patients ineligible for standard anticoagulation:randomly assigned to very low intensity anticoagulation(INR 1.1-1.6) or aspirin(150mg/d).

Simple aveugle

Parallel groups

Sample size: 122/131

Primary endpoint: stroke,systemic embolism,major haemorrhage and vascular death

FU duration: 2.7 years

The study was carried out to show that aspirin is equivalent to warfarin, but the methodology used was inappropriate.The study team conducted an intention to treat analysis and assumed they could conclude to equivalence if no significant difference was found between treatments at the end of the study.But this hypothesis is wrong :if no difference has been found,no conclusion is possible,and particularly, equivalence can't be proven.

haemorragic stroke(or intracerebral hemorrhage) 0.26 [0.14; 0.49]

fatal stroke(ischemic+hemorrhagic) 0.67 [0.51; 0.89]

non fatal stroke 0.63 [0.43; 0.92]

fatal bleeding 0.82 [0.67; 1.00]

thrombo-embolic event (cerebral or systemic) 0.66 [0.53; 0.82]

ischemic stroke 0.76 [0.59; 0.97]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.64 [0.51; 0.81]

Life threatening major bleeding 0.82 [0.67; 1.00]

Gastrointestinal major bleeding 1.50 [1.20; 1.89]

all death 0.88 [0.77; 1.00]

coronary events 1.29 [0.99; 1.69]

vascular death 0.85 [0.72; 1.00]

major bleeding 0.93 [0.81; 1.07]

Non–life threatening Major bleeding 1.08 [0.90; 1.30]

systemic thrombo-embolic complication 0.85 [0.39; 1.84]

haemorragic stroke(intracerebral hemorrhage) 0.27 [0.10; 0.72]

intra cranial hemorrhage(intracerebral hemorrhage + hematomas) 0.41 [0.21; 0.80]

thromboembolic event(cerebral or systemic) 0.76 [0.53; 1.09]

thromboembolic event*(TE event or ischemic stroke or systemic thromboembolic event) 0.76 [0.53; 1.09]

haemorragic stroke(intracerebral hemorrhage) 0.11 [0.03; 0.44]

intra cranial hemorrhage(intracerebral hemorrhage + hematomas) 0.20 [0.08; 0.48]

thromboembolic event(cerebral or systemic) 0.85 [0.59; 1.22]

thromboembolic event*(TE event or ischemic stroke or systemic thromboembolic event) 0.85 [0.59; 1.22]

dabigatran 150 mg twice daily (alone or combined with 81- or 325-mg aspirin) (n=166)

vs.

warfarin administered to achieve an international normalized ratio of 2 to 3 for (n=70)

factorial design: Three doses of dabigatran etexilate (50, 150, and 300 mg twice daily) were combined in a 3 3 factorial fashion with no aspirin or 81- or 325-mg aspirin once daily.

double blind

Factorial plan

Sample size: 166/70

Primary endpoint: bleedings

FU duration: 12 weeks

dabigatran 150 mg twice a day (n=6076)

vs.

warfarin adjusted-dose to a 2.0 to 3.0 INR (n=6022)

3 arms: dabigatran 110 mg, 150mg and warfarin

open (blind assessment)

Parallel groups

Sample size: 6076/6022

Primary endpoint: stroke or systemic embolism

FU duration: 2 y (median)

dabigatran 150mg daily (n=-9)

vs.

warfarin (n=-9)

open

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration: 2 y

sub group ( 20% of the overall study population in RE-LY)

dabigatran 110mg daily (n=-9)

vs.

warfarin (n=-9)

open

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration: 2 y

sub group ( 20% of the overall study population in RE-LY)

Four Fixed Dose Regimens of edoxaban (DU-176b) (n=1146)

vs.

warfarin (n=0)

double-blind

Parallel groups

Sample size: 1146/0

Primary endpoint: clinically relevant bleeding, •Laboratory marked abnormalities

FU duration: 3 months

phase 2

thromboembolic event(cerebral or systemic) 0.98 [0.80; 1.19]

thromboembolic event*(TE event or ischemic stroke or systemic thromboembolic event) 0.98 [0.80; 1.19]

rivaroxaban (n=3892)

vs.

warfarin INR 2-3 (n=3875)

double-blind

Parallel groups

Sample size: 3892/3875

Primary endpoint:

FU duration:

thrombo-embolic event (central or systemic)and fatal or intracranial hemorrhage 0.74 [0.31; 1.81]

non fatal TE events,bleedings and vascular death* 0.74 [0.31; 1.81]

vascular death 1.53 [0.56; 4.22]

major bleeding 5.11 [0.60; 43.30]

fatal bleeding ∞ [NaN; ∞]

thrombo-embolic event (cerebral or systemic) 0.56 [0.21; 1.48]

ischemic stroke 0.57 [0.19; 1.66]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.56 [0.21; 1.48]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.68 [0.25; 1.88]

systemic thrombo-embolic complication 0.51 [0.05; 5.58]

vascular death 0.20 [0.06; 0.69]

thrombo-embolic event (cerebral or systemic) 0.44 [0.22; 0.88]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.44 [0.22; 0.88]

major bleeding ∞ [NaN; ∞]

haemorragic stroke(or intracerebral hemorrhage) ∞ [NaN; ∞]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.48 [0.22; 1.03]

all death 0.42 [0.21; 0.82]

ischemic stroke 0.15 [0.03; 0.66]

major bleeding 1.96 [0.18; 21.48]

haemorragic stroke(or intracerebral hemorrhage) NaN [NaN; NaN]

fatal stroke(ischemic+hemorrhagic) 0.00 [0.00; NaN]

fatal bleeding 0.98 [0.06; 15.58]

thrombo-embolic event (cerebral or systemic) 0.33 [0.14; 0.83]

ischemic stroke 0.35 [0.14; 0.88]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.33 [0.14; 0.83]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.42 [0.19; 0.94]

all death 0.75 [0.27; 2.13]

vascular death 0.57 [0.17; 1.93]

major bleeding 1.00 [0.25; 3.96]

haemorragic stroke(or intracerebral hemorrhage) ∞ [NaN; ∞]

fatal bleeding ∞ [NaN; ∞]

systemic thrombo-embolic complication 0.00 [0.00; NaN]

fatal stroke(ischemic+hemorrhagic) 1.02 [0.06; 16.21]

systemic thrombo-embolic complication 0.57 [0.26; 1.27]

all death 0.86 [0.55; 1.36]

haemorragic stroke(or intracerebral hemorrhage) 1.00 [0.14; 7.06]

fatal stroke(ischemic+hemorrhagic) 1.75 [0.52; 5.92]

systemic thrombo-embolic complication 1.00 [0.29; 3.42]

warfarin standard dose (target INR 2-3) (n=187)

vs.

placebo (n=191)

Double blind

Parallel groups

Sample size: 187/191

Primary endpoint: nonlacunar stroke,noncentral nervous systemic embolism and fatal or intracranial hemorrhage

FU duration: 15.2 months

There was in each center an unblinded anticoagulation supervisor who received the PT and regulated the warfarin doses to maintain INR btw 2-3.For patients given placebo the PT were ignored but the dose of medication was modified according to a series of sequential sham PT . Five randomized patients did not have AF(2 in warfarin group and 3 in placebo group), were judged ineligible and have not been included in the analysis.No event occured to these patients.The number of lost to follow up was not given. Early permanent discontinuation of the study medication not due to a primary outcome event occured in 26.2% warfarin treated patients and 22.5% placebo-treated patients.

warfarin standard dose(target INR:2.8-4.2) (n=335)

vs.

control (n=336)

The AFASAK study compared 3 different treatments:aspirin, warfarin and placebo.

Open

Parallel groups

Sample size: 335/336

Primary endpoint: thrombo-embolic complication

FU duration: 2 years

The number of lost to follow up is not given.

warfarin low dose (target INR:1.5-2.7) (n=212)

vs.

no placebo.people received no treatment but could choose to take aspirin. (n=208)

9 patients were excluded after randomization.

Open

Parallel groups

Sample size: 212/208

Primary endpoint: ischemic stroke

FU duration: 2.2 years

warfarin standard dose(target INR:2.0-4.5) (n=210)

vs.

control (n=211)

The SPAF study compared 3 treatments: warfarin,aspirin and placebo. 2 groups were considered: -G1: in which patients received either warfarin,aspirin or placebo -G2: in which patients received either aspirin or placebo(these patients were uneligible to take warfarin) No analysis was made between warfarin and aspirin. Warfarin is compared only with the G1 placebo.

Patients with history of stroke or TIA more than 2 years before entry were elgible(7% of patients).So,it is mostly a primary prevention trial but not only.

Open

Parallel groups

Sample size: 210/211

Primary endpoint: ischemic stroke and systemic embolism

FU duration: 1.3 years

warfarin low dose(target INR 1.4-2.8) (n=260)

vs.

placebo (n=265)

The first 12 weeks constituted a medication induction period .Only patients who reached a baseline PT in the normal range were included in the study.

Double blind

Parallel groups

Sample size: 260/265

Primary endpoint: cerebral infarction

FU duration: 1.75 years

To maintain blinding,adjustment were made in the dose of placebo according to randomly assigned prearranged schedules. 13 patients were excluded after randomization. There are 19 lost to follow up(12 in placebo group,7 in warfarin group). The datas on patients lost to follow up were censored at the time of their last study visit. 55 patients withdrew from the study at their own request:data on these patients were censored at the time of their last visit.

warfarin low dose (1.25 mg/d) + aspirin 75 mg/d (n=334)

vs.

no treatment (n=334)

Open

Parallel groups

Sample size: 334/334

Primary endpoint: stroke

FU duration: 33 months

non fatal TE events,bleedings and vascular death* 1.19 [0.57; 2.49]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 1.53 [0.44; 5.31]

non fatal TE events,bleedings and vascular death* 0.99 [0.46; 2.15]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 1.99 [0.61; 6.48]

non fatal TE events,bleedings and vascular death* 1.79 [1.22; 2.63]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 4.02 [2.10; 7.69]

non fatal TE events,bleedings and vascular death* 1.70 [0.63; 4.56]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) ∞ [NaN; ∞]

warfarin fixed low dose (1.25 mg/d) (n=167)

vs.

warfarin standard dose(target INR 2-3) (n=170)

The trial includes 4 arms:fixed low dose warfarin (1.25mg/d),fixed low dose warfarin (1.25mg/d)+ aspirin 300mg,aspirin 300 mg and conventional warfarin therapy(target INR 2-3). The protocol allows 4 weeks per year without study treatment.

Open

Parallel groups

Sample size: 167/170

Primary endpoint: all stroke or systemic thromboembolic event

FU duration: 3.5 years

Mean follow-up duration was not reported. The discontinuation of study treatment was reported globally(25.1% for reasons other than primary or secondary adverse events).Though the primary analysis of the study was made according to an "on treatment" approach ,an "intention to treat" analysis was performed for thrombo-embolic events to allow comparison with other studies.

warfarin fixed low dose(1.25mg/d) + aspirin(300mg/d) (n=171)

vs.

warfarin standard dose(target INR 2.0-3.0) (n=170)

The trial includes 4 arms:fixed low dose warfarin (1.25mg/d),fixed low dose warfarin (1.25mg/d)+ aspirin 300mg,aspirin 300 mg and conventional warfarin therapy(target INR 2-3). The protocol allows 4 weeks per year without study treatment.

Open

Parallel groups

Sample size: 171/170

Primary endpoint: stroke or systemic thromboembolic event

FU duration: 3.5 years

Mean follow-up duration was not reported. The discontinuation of study treatment was reported globally(25.1% for reasons other than primary or secondary adverse events). Though the primary analysis of the study was made according to an "on treatment" approach ,an "intention to treat" analysis was performed for thrombo-embolic events to allow comparison with other studies.

warfarin low dose(target INR 1.2-1.5)+ aspirin 325 mg/d (n=521)

vs.

warfarin standard dose(target INR 2.0-3.0) (n=523)

36%(warfarin arm) and 40%(warfarin + aspirin arm)of patients had a history of previous embolism, so it was not only a primary prevention trial.

Open

Parallel groups

Sample size: 521/523

Primary endpoint: ischaemic stroke or systemic embolism

FU duration: 1.1 years

72 patients were withdrawn from study treatment but still followed up for the intention to treat analysis. The hypothesis put forward was to show that combined therapy was as efficacious as adjusted dose warfarin, but no threshold is specified.

warfarin low dose (1.25mg/d) (n=150)

vs.

warfarin standard dose( target INR 2.0-3.0) (n=153)

Open

Parallel groups

Sample size: 150/153

Primary endpoint: thromboembolic event,cerebral or fatal bleeding and vascular death

FU duration: 14.5 months

Withdrawal from study treatment is reported here only unrelated to primary or secondary endpoints.

vascular death 0.80 [0.38; 1.68]

major bleeding ∞ [NaN; ∞]

haemorragic stroke(or intracerebral hemorrhage) NaN [NaN; NaN]

thrombo-embolic event (cerebral or systemic) 0.84 [0.48; 1.47]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.84 [0.48; 1.47]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.84 [0.44; 1.61]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.92 [0.55; 1.55]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.06 [0.01; 0.42]

aspirin 75 mg/d (n=336)

vs.

placebo (n=336)

The AFASAK study compared 3 different treatments:aspirin, warfarin and placebo.

Double aveugle

Parallel groups

Sample size: 336/336

Primary endpoint: thrombo-embolic complication

FU duration: 2 years

The number of lost to follow up is not given.

aspirin:125mg/day(group A1);125mg on alternate days(group A2) (n=-9)

vs.

no control treatment(group C) (n=-9)

Open

Sample size: -9/-9

Primary endpoint:

FU duration:

aspirin 325mg/d (n=346)

vs.

placebo (n=357)

The SPAF study compared 3 treatments :warfarin,aspirin and placebo. 2 groups were considered: -G1: in which patients received either warfarin,aspirin or placebo -G2: in which patients received either aspirin or placebo(these patients were uneligible to take warfarin) No analysis was made between warfarin and aspirin. All patients under aspirin were compared to all patients under placebo(G1+G2)

Patients with history of stroke or TIA more than 2 years before entry were eligible(7% of patients).So,it is mainly a primary prevention trial.

Double blind

Parallel groups

Sample size: 346/357

Primary endpoint: ischemic stroke and systemic embolism

FU duration: 1.3 years

aspirin 325mg/d (n=206)

vs.

placebo (n=211)

The SPAF study compared 3 treatments :warfarin,aspirin and placebo. 2 groups were considered: -G1: in which patients received either warfarin,aspirin or placebo -G2: in which patients received either aspirin or placebo(these patients were uneligible to take warfarin) No analysis was made between warfarin and aspirin. All patients under aspirin were compared to all patients under placebo(G1+G2)

Patients with history of stroke or TIA more than 2 years before entry were eligible(7% of patients).So,it is mostly a primary prevention trial but not only.

Double blind

Parallel groups

Sample size: 206/211

Primary endpoint: ischemic stroke and systemic embolism

FU duration: 1.3 years

non fatal TE events,bleedings and vascular death* 1.03 [0.72; 1.48]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 1.26 [0.68; 2.33]

non fatal TE events,bleedings and vascular death* 0.71 [0.32; 1.54]

all death 2.31 [0.91; 5.86]

vascular death 1.32 [0.30; 5.80]

major bleeding 1.65 [0.40; 6.78]

haemorragic stroke(or intracerebral hemorrhage) ∞ [NaN; ∞]

fatal stroke(ischemic+hemorrhagic) 0.99 [0.14; 6.93]

thrombo-embolic event (cerebral or systemic) 0.82 [0.26; 2.65]

ischemic stroke 0.82 [0.26; 2.65]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.82 [0.26; 2.65]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.64 [0.28; 1.43]

systemic thrombo-embolic complication 0.99 [0.06; 15.67]

non fatal TE events,bleedings and vascular death* 1.25 [0.81; 1.95]

fatal stroke(ischemic+hemorrhagic) ∞ [NaN; ∞]

non fatal stroke 1.31 [0.65; 2.66]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 1.50 [0.78; 2.91]

non fatal TE events,bleedings and vascular death* 0.84 [0.37; 1.89]

fatal stroke(ischemic+hemorrhagic) ∞ [NaN; ∞]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 1.26 [0.34; 4.60]

non fatal TE events,bleedings and vascular death* 1.11 [0.50; 2.49]

fatal stroke(ischemic+hemorrhagic) ∞ [NaN; ∞]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 1.55 [0.38; 6.35]

non fatal TE events,bleedings and vascular death* 0.98 [0.60; 1.58]

non fatal stroke 1.40 [0.68; 2.87]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 1.35 [0.69; 2.63]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 1.90 [0.93; 3.89]

aspirin 300mg/d (n=319)

vs.

coumarin low dose(target INR 1.1-1.6 ) (n=279)

The PATAF trial includes 2 strata: -patients eligible for standard intensity coumarin:randomly assigned to standard anticoagulation(INR 2.5-3.5),very low intensity anticoagulation(INR 1.1-1.6) or aspirin(150mg/d). -patients ineligible for standard anticoagulation:randomly assigned to very low intensity anticoagulation(INR 1.1-1.6) or aspirin(150mg/d).

We took all patients who were given aspirin (strate 1+2) and all patients on low dose anticoagulation(strate 1+2).

Simple aveugle

Parallel groups

Sample size: 319/279

Primary endpoint: stroke,systemic embolism,major haemorrhage and vascular death

FU duration: 2.7 years

The study was carried out to show that aspirin is equivalent to warfarin, but the methodology used was inappropriate.The study team conducted an intention to treat analysis and assumed they could conclude to equivalence if no significant difference was found between treatments at the end of the study.But this hypothesis is wrong :if no difference has been found,no conclusion is possible,and particularly, equivalence can't be proven.

aspirin 300 mg/d (n=169)

vs.

warfarin low dose (1.25mg/d) (n=167)

The trial includes 4 arms: fixed low dose warfarin (1.25mg/d),fixed low dose warfarin (1.25mg/d)+ aspirin 300mg,aspirin 300 mg and conventional warfarin therapy(target INR 2-3). The protocol allows 4 weeks per year without study treatment.

Open

Parallel groups

Sample size: 169/167

Primary endpoint: all stroke or systemic thromboembolic event

FU duration: 3.5 years

Mean follow-up duration was not reported. The discontinuation of study treatment was reported globally(25.1% for reasons other than primary or secondary adverse events). Though the primary analysis of the study was made according to an "on treatment" approach ,an "intention to treat" analysis was performed for thrombo-embolic events to allow comparison with other studies.

aspirin 325 mg/d (n=357)

vs.

warfarin standard dose(target INR 2.0-4.5) (n=358)

Open

Parallel groups

Sample size: 357/358

Primary endpoint: ischemic stroke and systemic embolism

FU duration: 3.1 years

Randomisation was not centralized. 61.9%(681) patients of this study are stemming from the SPAF I study:416 had been assigned to warfarin or aspirin in the warfarin eligible group and have been included without rerandomization in SPAF II(patients aged 75 and less' strate);265 had been assigned mostly to placebo and have been rerandomized to get either aspirin or warfarin. The withdrawals from trial are not reported.

aspirin 300 mg/d (n=169)

vs.

warfarin standard dose(target INR 2-3) (n=170)

The trial includes 4 arms:fixed low dose warfarin (1.25mg/d),fixed low dose warfarin (1.25mg/d)+ aspirin 300mg,aspirin 300 mg and conventional warfarin therapy(target INR 2-3). The protocol allows 4 weeks per year without study treatment.

Open

Parallel groups

Sample size: 169/170

Primary endpoint: stroke or systemic thromboembolic event

FU duration: 3.5 years

Mean follow-up duration was not reported. The discontinuation of study treatment was reported globally(25.1% for reasons other than primary or secondary adverse events).Though the primary analysis of the study was made according to an "on treatment" approach ,an "intention to treat" analysis was performed for thrombo-embolic events to allow comparison with other studies.

aspirin 150mg/d (n=141)

vs.

coumarin standard dose(target INR 2.5-3.5) (n=131)

The PATAF trial includes 2 strata: -patients eligible for standard intensity coumarin:randomly assigned to standard anticoagulation(INR 2.5-3.5),very low intensity anticoagulation(INR 1.1-1.6) or aspirin(150mg/d). -patients ineligible for standard anticoagulation:randomly assigned to very low intensity anticoagulation(INR 1.1-1.6) or aspirin(150mg/d).

Simple aveugle

Parallel groups

Sample size: 141/131

Primary endpoint: stroke,systemic embolism,major haemorrhage and vascular death

FU duration: 2.7 years

The study was carried out to show that aspirin is equivalent to warfarin, but the methodology used was inappropriate.The study team conducted an intention to treat analysis and assumed they could conclude to equivalence if no significant difference was found between treatments at the end of the study.But this hypothesis is wrong :if no difference has been found,no conclusion is possible,and particularly, equivalence can't be proven.

aspirin 325 mg/d (n=188)

vs.

warfarin standard dose (target INR 2.0-4.5) (n=197)

Open

Parallel groups

Sample size: 188/197

Primary endpoint: ischemic stroke and systemic embolism

FU duration: 2.0 years

Randomization was not centralized. 61.9%(681) patients of this study are stemming from the SPAF I study:416 had been assigned to warfarin or aspirin in the warfarin eligible group and have been included without rerandomization in SPAF II(patients aged 75 and less' strate);265 had been assigned mostly to placebo and have been rerandomized to get either aspirin or warfarin. The withdrawals from trial are not reported.

aspirin (low dose 75 mg) (n=336)

vs.

warfarin standard dose(target INR 2.8-4.2) (n=335)

The AFASAK study compared 3 different treatments:aspirin, warfarin and placebo.

Open

Parallel groups

Sample size: 336/335

Primary endpoint: thrombo-embolic complication

FU duration: 2 years

The number of lost to follow up is not given. There is a high number of withdrawn patients, even higher in the warfarin arm(38% for warfarin,13% for aspirin,15% for placebo)).

haemorragic stroke(or intracerebral hemorrhage) 0.34 [0.12; 0.93]

non fatal TE events,bleedings and vascular death* 1.39 [1.18; 1.64]

thrombo-embolic event (cerebral or systemic) 1.43 [1.18; 1.74]

ischemic stroke 2.17 [1.51; 3.11]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 1.71 [1.25; 2.36]

all death 1.02 [0.82; 1.26]

vascular death 1.14 [0.89; 1.48]

major bleeding 1.10 [0.83; 1.45]

fatal stroke(ischemic+hemorrhagic) 0.94 [0.46; 1.95]

fatal bleeding 0.64 [0.25; 1.66]

clopidogrel (75 mg per day) plus aspirin (75–100 mg per day) (n=3335)

vs.

oral anticoagulation therapy (target international normalised ratio of 2·0–3·0) (n=3371)

open

Parallel groups

Sample size: 3335/3371

Primary endpoint: stroke, non-CNS systemic embolus

FU duration: 1.28 y (median)

non fatal TE events,bleedings and vascular death* 1.45 [0.77; 2.72]

non fatal stroke 3.29 [0.92; 11.81]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 2.12 [0.88; 5.09]

Triflusal 600 mg/d (n=242)

vs.

coumadin standard dose(target INR 2-3) (n=237)

Open

Parallel groups

Sample size: 242/237

Primary endpoint: vascular death,TIA,nonfatal stroke or systemic embolism

FU duration: 2.76 years

Withdrawals from study treatments are not reported separetely:9% were withdrawn for adverse events without significant difference among groups,9.3% were withdrawn secondary to gp or patient's decision.

major bleeding 2.67 [1.74; 4.08]

fatal bleeding 7.14 [1.61; 31.58]

all death 1.12 [0.79; 1.58]

fatal stroke(ischemic+hemorrhagic) 0.00 [0.00; NaN]

thrombo-embolic event (cerebral or systemic) 0.73 [0.40; 1.32]

ischemic stroke 0.71 [0.36; 1.43]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.73 [0.40; 1.32]

systemic thrombo-embolic complication 0.00 [0.00; NaN]

subcutaneous idraparinux 2·5 mg weekly (n=2283)

vs.

adjusted-dose vitamin K antagonists (target of an international normalised ratio of 2–3) (n=2293)

open

Parallel groups

Sample size: 2283/2293

Primary endpoint: all stroke and systemic embolism

FU duration: 10.7 months

Freedom from arrhythmia at 12 months per protocol 11.13 [4.27; 29.03]

Freedom from arrhythmia at 12 months worst case 11.13 [4.27; 29.03]

Freedom from arrhythmia at 12 months ITT 11.13 [4.27; 29.03]

death 0.00 [0.00; NaN]

atrial tachyarrhythmia recurrence free survival 4.22 [2.14; 8.32]

Freedom from arrhythmia at 12 months per protocol 2.36 [1.50; 3.70]

Freedom from arrhythmia at 12 months worst case 2.09 [1.38; 3.17]

Freedom from arrhythmia at 12 months ITT 2.17 [1.44; 3.27]

death NaN [NaN; NaN]

adverse clinical event 1.09 [0.30; 4.01]

adverse clinical event 0.22 [0.09; 0.55]

atrial tachyarrhythmia recurrence free survival 3.86 [2.65; 5.63]

Freedom from arrhythmia at 12 months per protocol 2.43 [1.84; 3.21]

Freedom from arrhythmia at 12 months worst case 2.43 [1.84; 3.21]

Freedom from arrhythmia at 12 months ITT 1.38 [1.22; 1.56]

death NaN [NaN; NaN]

atrial tachyarrhythmia recurrence free survival 6.43 [2.91; 14.21]

Freedom from arrhythmia at 12 months per protocol 9.14 [3.44; 24.23]

Freedom from arrhythmia at 12 months worst case 6.09 [2.74; 13.51]

Freedom from arrhythmia at 12 months ITT 6.43 [2.91; 14.21]

death 0.51 [0.05; 5.47]

adverse clinical event 0.76 [0.18; 3.27]

atrial tachyarrhythmia recurrence free survival 2.00 [1.02; 3.91]

Freedom from arrhythmia at 12 months ITT 2.00 [1.02; 3.91]

death NaN [NaN; NaN]

adverse clinical event 0.71 [0.29; 1.75]

Freedom from arrhythmia at 12 months per protocol 1.96 [1.00; 3.87]

Freedom from arrhythmia at 12 months worst case 1.83 [0.92; 3.66]

atrial tachyarrhythmia recurrence free survival 3.20 [1.71; 6.00]

Symptomatic Atrial Arrhythmia 0.24 [0.15; 0.39]

Any Atrial Arrhythmia 0.29 [0.18; 0.46]

death ∞ [NaN; ∞]

Freedom from arrhythmia at 12 months per protocol 17.03 [5.59; 51.90]

Freedom from arrhythmia at 12 months worst case 17.03 [5.59; 51.90]

Freedom from arrhythmia at 12 months ITT 1.28 [1.00; 1.62]

death ∞ [NaN; ∞]

atrial tachyarrhythmia recurrence free survival 1.87 [1.23; 2.83]

Freedom from arrhythmia at 12 months per protocol 1.87 [1.23; 2.83]

Freedom from arrhythmia at 12 months worst case 1.87 [1.23; 2.83]

Freedom from arrhythmia at 12 months ITT 1.87 [1.23; 2.83]

death NaN [NaN; NaN]

AF recurrence 0.53 [0.46; 0.61]

death or CV hospitalization, 0.83 [0.74; 0.93]

net benefit 0.86 [0.65; 1.14]

death 0.85 [0.60; 1.21]

death, stroke,stroke, serious bleeding, cardiac arrest 0.86 [0.65; 1.14]

catheter ablation (n=53)

vs.

antiarrhythmic drugs (n=59)

open

Parallel groups

Sample size: 53/59

Primary endpoint: none defined

FU duration: 12 months

Pulmonary vein isolation (n=32)

vs.

Flecainide, propafenone, or sotalol; amiodarone if needed (n=35)

open

Parallel groups

Sample size: 32/35

Primary endpoint:

FU duration: 12 months

left atrial catheter ablation (n=99)

vs.

Flecainide acetate, propafenone hydrochloride, or sotalol hydrochloride (n=99)

open

Parallel groups

Sample size: 99/99

Primary endpoint:

FU duration: 12 months

left atrial catheter ablation plus amiodarone or other drugs (n=68)

vs.

Amiodarone or other drugs (n=69)

open blinded assessment

Parallel groups

Sample size: 68/69

Primary endpoint:

FU duration: 12 months

left atrial catheter ablation (n=15)

vs.

amiodarone (n=15)

open

Sample size: 15/15

Primary endpoint: sinus rhythm

FU duration: 12 months

catheter ablation (n=106)

vs.

antiarrhythmic drug therapy with a class I or III drug (n=61)

open

Parallel groups

Sample size: 106/61

Primary endpoint: treatment failure

FU duration: 9 months

circumferential pulmonary-vein ablation and amiodarione (n=77)

vs.

amiodarone and two cardioversions during the first three months alone (n=69)

open

Parallel groups

Sample size: 77/69

Primary endpoint:

FU duration: 12 months

pulmonary vein isolation (n=35)

vs.

antiarrhythmic drug treatment (n=35)

open

Parallel groups

Sample size: 35/35

Primary endpoint: first AF recurrence

FU duration: 12 months

(n=138)

vs.

(n=139)

Parallel groups

Sample size: 138/139

Primary endpoint:

FU duration:

left atrial catheter ablation (n=2204)

vs.

current state-of-the-art therapy with either rate control or rhythm control drugs (n=0)

open

Parallel groups

Sample size: 2204/0

Primary endpoint: all-cause mortality, disabling stroke, serious bleeding, or cardiac arrest

FU duration:

cryo-balloon catheter for pulmonary vein isolation (n=163)

vs.

nonfailed antiarrhythmic drugs (n=82)

open

Parallel groups

Sample size: 163/82

Primary endpoint: treatment succes

FU duration: 12 mo

all death 0.89 [0.81; 0.98] Demonstrated

major bleeding 0.70 [0.61; 0.81] Demonstrated

thrombo-embolic event (cerebral or systemic) 0.80 [0.67; 0.95] Demonstrated

thrombo-embolic event (central or systemic)and fatal or intracranial hemorrhage 0.78 [0.70; 0.87]

haemorragic stroke(or intracerebral hemorrhage) 0.51 [0.35; 0.75]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.79 [0.66; 0.95]

major and clinically relevant non-major bleeding 0.70 [0.63; 0.77]

coronary events 0.88 [0.66; 1.17]

ischemic stroke 0.92 [0.75; 1.14]

Gastrointestinal major bleeding 0.88 [0.68; 1.14]

systemic thrombo-embolic complication 0.88 [0.44; 1.76]

apixaban 5mg twice daily (n=9120)

vs.

warfarin adjusted for an INR between 2 and 3 (n=9081)

double blind

Parallel groups

Sample size: 9120/9081

Primary endpoint: stroke or systemic embolism

FU duration: 1.8 yrs (median)

apixaban 5 or 2.5 mg twice daily (n=222)

vs.

warfarin (n=0)

double blind

Parallel groups

Sample size: 222/0

Primary endpoint: major or clinically relevant non-major bleeding

FU duration: 12 weeks

phase 2

vascular death,TIA,nonfatal stroke or systemic embolism 0.66 [0.53; 0.83]

thrombo-embolic event (cerebral or systemic) 0.46 [0.33; 0.64]

ischemic stroke 0.37 [0.25; 0.55]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.46 [0.33; 0.65]

all death 0.79 [0.62; 1.01]

coronary events 0.85 [0.50; 1.47]

vascular death 0.86 [0.64; 1.16]

major bleeding 1.14 [0.74; 1.75]

haemorragic stroke(or intracerebral hemorrhage) 0.66 [0.24; 1.86]

fatal bleeding 0.84 [0.26; 2.72]

Gastrointestinal major bleeding 0.85 [0.39; 1.84]

apixaban 5 mg (or 2.5 mg) twice daily (n=2808)

vs.

aspirin 81-324 md daily (n=2791)

double blind

Parallel groups

Sample size: 2808/2791

Primary endpoint: stroke or systemic embolism

FU duration: maximum 21 months

major bleeding 0.80 [0.69; 0.93]

haemorragic stroke(or intracerebral hemorrhage) 0.31 [0.17; 0.56]

Life threatening major bleeding 0.68 [0.56; 0.84]

all death 0.91 [0.80; 1.03]

vascular death 0.90 [0.77; 1.06]

fatal stroke(ischemic+hemorrhagic) 0.95 [0.74; 1.23]

non fatal stroke 0.87 [0.62; 1.23]

thrombo-embolic event (cerebral or systemic) 0.91 [0.74; 1.11]

ischemic stroke 1.11 [0.89; 1.39]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.92 [0.75; 1.12]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.92 [0.74; 1.14]

Gastrointestinal major bleeding 1.11 [0.87; 1.42]

Non–life threatening Major bleeding 0.95 [0.79; 1.15]

systemic thrombo-embolic complication 0.79 [0.36; 1.73]

dabigatran 110 mg twice a day (n=6015)

vs.

warfarin adjusted dose to a 2-3 INR (n=6022)

3 arms: dabigatran 110 mg, 150mg and warfarin

open (blind assessment)

Parallel groups

Sample size: 6015/6022

Primary endpoint: stroke or systemic embolism

FU duration: 2 y (median)

Dabigatran 110, 220, 300 mg twice daily (n=-9)

vs.

warfarin (n=-9)

open

Parallel groups

Sample size: -9/-9

Primary endpoint: major bleeding event, ,

FU duration:

vascular death 0.86 [0.77; 0.97]

major bleeding 0.80 [0.71; 0.91]

haemorragic stroke(or intracerebral hemorrhage) 0.47 [0.35; 0.64]

fatal bleeding 0.55 [0.36; 0.84]

Life threatening major bleeding 0.51 [0.38; 0.69]

major and clinically relevant non-major bleeding 0.86 [0.80; 0.92]

Gastrointestinal major bleeding 1.23 [1.01; 1.49]

all death 0.92 [0.83; 1.01]

fatal stroke(ischemic+hemorrhagic) 0.92 [0.68; 1.25]

thrombo-embolic event (cerebral or systemic) 0.87 [0.73; 1.04]

ischemic stroke 1.00 [0.84; 1.20]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.88 [0.75; 1.03]

systemic thrombo-embolic complication 0.65 [0.34; 1.24]

edoxaban 60mg once daily (n=7035)

vs.

warfarin (INR 2-3) (n=7036)

a third arm received a low dose of edoxaban, 30mg. The allocated dose was halved if any of the following characteristics were present at the time of randomization or during the study: estimated creatinine clearance of 30 to 50 ml per minute, a body weight of 60 kg or less, or the concomitant use of verapamil or quinidine (potent P-glycoprotein inhibitors)

double blind

Parallel groups

Sample size: 7035/7036

Primary endpoint: stroke, systemic embolic events and all-cause mortality

FU duration: 2.8 years

edoxaban (DU-176b) (n=-9)

vs.

warfarin (n=-9)

double-blind

Parallel groups

Sample size: -9/-9

Primary endpoint: all bleeding

FU duration:

haemorragic stroke(or intracerebral hemorrhage) 0.58 [0.38; 0.89]

fatal bleeding 0.50 [0.31; 0.80]

Life threatening major bleeding 0.69 [0.53; 0.89]

Gastrointestinal major bleeding 1.46 [1.19; 1.78]

vascular death,TIA,nonfatal stroke or systemic embolism 0.94 [0.84; 1.05]

all death 0.92 [0.82; 1.03]

coronary events 0.80 [0.62; 1.04]

vascular death 0.94 [0.81; 1.09]

major bleeding 1.04 [0.90; 1.20]

fatal stroke(ischemic+hemorrhagic) 0.70 [0.49; 1.02]

thrombo-embolic event (cerebral or systemic) 0.88 [0.75; 1.04]

ischemic stroke 0.99 [0.82; 1.20]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.84 [0.69; 1.01]

major and clinically relevant non-major bleeding 1.03 [0.96; 1.11]

systemic thrombo-embolic complication 0.74 [0.42; 1.31]

Rivaroxaban 20mg p.o. once daily (n=7131)

vs.

Warfarin p.o. once daily titrated to a target INR of 2.5 (range 2.0 to 3.0, inclusive) (n=7133)

double blind

Parallel groups

Sample size: 7131/7133

Primary endpoint: stroke or non-CNS systemic embolism

FU duration: median 1.94 y

non fatal TE events,bleedings and vascular death* 0.71 [0.48; 1.07]

all death 0.99 [0.73; 1.34]

coronary events 1.85 [0.94; 3.61]

vascular death 1.21 [0.77; 1.91]

major bleeding 0.71 [0.44; 1.13]

haemorragic stroke(or intracerebral hemorrhage) 0.44 [0.14; 1.44]

fatal stroke(ischemic+hemorrhagic) 1.11 [0.45; 2.73]

thrombo-embolic event (cerebral or systemic) 0.71 [0.48; 1.07]

ischemic stroke 0.70 [0.45; 1.09]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 0.70 [0.45; 1.09]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.67 [0.44; 1.01]

systemic thrombo-embolic complication 2.00 [0.37; 10.90]

hypertransaminasemia 7.81 [4.58; 13.32]

non fatal TE events,bleedings and vascular death* 1.38 [0.91; 2.10]

all death 0.94 [0.74; 1.21]

coronary events 0.70 [0.43; 1.16]

major bleeding 0.75 [0.54; 1.03]

haemorragic stroke(or intracerebral hemorrhage) 1.00 [0.14; 7.10]

fatal stroke(ischemic+hemorrhagic) 3.34 [0.92; 12.11]

thrombo-embolic event (cerebral or systemic) 1.38 [0.91; 2.10]

ischemic stroke 1.25 [0.81; 1.93]

thromboembolic event likes(TE event or ischemic stroke or systemic embolism) 1.25 [0.81; 1.93]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 1.24 [0.81; 1.89]

systemic thrombo-embolic complication 6.01 [0.72; 49.84]

ximelegatran 20,40,60 mg twice daily (n=187)

vs.

warfarin standard dose(target INR 2-3) (n=67)

-treatment with either NSAI agents or fibrinolytic agents within the week before the start was prohibited -patient previously receiving warfarin were given ximelegatran once INR value was 1.5 or under/after the end of the study patients who stopped ximelegatran began warfarin 12 to 24 h after last intake.

-SPORTIF II is a dose guiding study -66 patient received 20mg,62 received 40mg,59 received 60 mg

Open

Parallel groups

Sample size: 187/67

Primary endpoint: Thrombo-embolic events and bleedings

FU duration: 16 weeks

it is a dose guiding study

ximelagatran 36 mg twice daily (n=1704)

vs.

warfarin standard dose (target INR 2-3) (n=1703)

Aspirin was used concurrently for at least half the period on study drug by 13% patients assigned to ximelagatran and 10% on warfarin(p=0.01).

Open

Parallel groups

Sample size: 1704/1703

Primary endpoint: All stroke or systemic embolism

FU duration: 17.4 months

Premature termination of study treatment was the result of study endpoint (4% warfarin group,3% ximelegatran) and adverse effects(4% warfarin group,8% ximelegatran group:this difference is related to elevation of liver enzymes in some patients treated with ximelegatran). The trial was a non inferiority trial but the primary analysis was only by intention to treat.

ximelegatran 36 mg twice daily (n=1960)

vs.

warfarin standard dose(target INR 2-3) (n=1962)

Double blind

Parallel groups

Sample size: 1960/1962

Primary endpoint: All stroke and systemic embolism

FU duration: 20 months

AF recurrence 0.62 [0.47; 0.81]

atorvastatin 80 mg daily (n=118)

vs.

placebo (n=116)

double blind

Parallel groups

Sample size: 118/116

Primary endpoint:

FU duration:

12 patients were excluded after randomization

candesartan 8 mg once daily for 3-6 weeks before and candesartan 16 mg once daily for 6 months after electrical cardioversion (n=86)

vs.

placebo (n=85)

double blind

Parallel groups

Sample size: 86/85

Primary endpoint: Recurrence of atrial fibrillation

FU duration: 6 months

AF recurrence 0.60 [0.37; 0.97]

enalapril (n=70)

vs.

control (n=75)

open

Parallel groups

Sample size: 70/75

Primary endpoint:

FU duration: 270 days (range 61-575d)

hospitalization for HF 0.87 [0.78; 0.98]

cardiovascular events + HF hospitalization 0.95 [0.89; 1.02]

vascular death 1.03 [0.93; 1.13]

stroke/MI/vascular death 1.00 [0.92; 1.08]

stroke 0.92 [0.81; 1.05]

MI 1.05 [0.84; 1.33]

irbesartan 300mg once daily (n=4518)

vs.

placebo (n=4498)

these patients were drawn from two parallel trials (ACTIVE-A and ACTIVE-W) utilizing a partial factorial design

double blind

Factorial plan

Sample size: 4518/4498

Primary endpoint: coprimary MACE, HF events

FU duration: 4.1 years

AF recurrence 0.39 [0.19; 0.79]

irbesartan (n=79)

vs.

control (n=75)

open

Parallel groups

Sample size: 79/75

Primary endpoint:

FU duration: 254 d (range 60-710)

AF recurrence 0.45 [0.13; 1.57]

lisinopril (n=7)

vs.

placebo (n=11)

double blind

Parallel groups

Sample size: 7/11

Primary endpoint:

FU duration: 84 days

AF recurrence 0.99 [0.89; 1.09]

more than 1 recurrence 0.96 [0.81; 1.14]

valsartan (n=722)

vs.

placebo (n=720)

double blind

Parallel groups

Sample size: 722/720

Primary endpoint: AF recurrence

FU duration: 1 year

AF 1.07 [0.76; 1.51]

gemfibrozil (n=1070)

vs.

placebo (n=1060)

double blind

Parallel groups

Sample size: 1070/1060

Primary endpoint:

FU duration: 4.4 y

AF 0.61 [0.45; 0.84]

AF 0.40 [0.09; 1.83]

AF 1.10 [0.63; 1.93]

atorvastatin 40mg daily (n=101)

vs.

placebo (n=99)

Sample size: 101/99

Primary endpoint: post-operative AF 5 min

FU duration: 30 days

atorvastatin 20mg daily (n=20)

vs.

placebo (n=20)

double-blind

Parallel groups

Sample size: 20/20

Primary endpoint:

FU duration: 3 weeks

atorvastatin 80mg daily (n=1421)

vs.

placebo (n=1440)

double-blind

Parallel groups

Sample size: 1421/1440

Primary endpoint:

FU duration: 16 weeks

AF recurrence 0.73 [0.58; 0.91]

AF recurrence 0.27 [0.09; 0.86]

AF recurrence 0.39 [0.25; 0.60]

atorvastatin 80 mg (n=118)

vs.

placebo (n=108)

double blind

Sample size: 118/108

Primary endpoint:

FU duration: 16 weeks

atorvastatin 10 mg (n=24)

vs.

standard therapy (n=24)

open

Sample size: 24/24

Primary endpoint: recurrence of AF

FU duration: 3 months

atorvastatin 20–40 mg (n=40)

vs.

placebo (n=40)

NA

Sample size: 40/40

Primary endpoint:

FU duration: 4–6 months

AF recurrence 1.06 [0.62; 1.81]

pravastatin 40 mg (n=51)

vs.

standard therapy (n=51)

Sample size: 51/51

Primary endpoint:

FU duration: 6 weeks