Mechanism

treatment

comparator

Warfarin

venous thrombosis, in all type of patients

Warfarin

venous thrombosis, in all type of patients

Warfarin

venous thrombosis, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	0.86 [0.56 1.33]	p=1.00	0	1869	7	Levine, LAFIT (Kearon), Agnelli, Agnelli, PREVENT (Ridker), ELAET (Kearon), DURAC (Schulman),
All cause death	0.86 [0.56 1.33]	p=1.00	0	1869	7	Levine, LAFIT (Kearon), Agnelli, Agnelli, PREVENT (Ridker), ELAET (Kearon), DURAC (Schulman),
Bleeding	no data
Bleeding	no data
In-hospital death	no data
Revascularization	no data
Major bleeding	2.75 [1.29 5.86]	p=0.04	0	1869	7	Levine, LAFIT (Kearon), Agnelli, Agnelli, PREVENT (Ridker), ELAET (Kearon), DURAC (Schulman),
Major bleeding	2.75 [1.29 5.86]	p=0.04	0	1869	7	Levine, LAFIT (Kearon), Agnelli, Agnelli, PREVENT (Ridker), ELAET (Kearon), DURAC (Schulman),
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	no data
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	no data
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	no data
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	1.65 [0.39 7.07]	p=1.00	0	267	1	Agnelli,
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	0.54 [0.38 0.75]	p=0.04	0	1869	7	Levine, LAFIT (Kearon), Agnelli, Agnelli, PREVENT (Ridker), ELAET (Kearon), DURAC (Schulman),

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
Levine, 1995	continuation for 2 months of warfarin adjusted INR value of 2.0 to 3.0	Discontinue oral anticoagulant therapy (after 1 months)	Patients with venographically confirmed acute proximal DVT who had received four weeks of warfarin after initial heparin and whose four week IPG was normal
LAFIT (Kearon), 1999	Continuation of the oral anticoagulant therapy up to 24 months, warfarin was adjusted to achieve a target INR between 2.0 and 3.0.	discontinuation (after 3 months)	patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism
Agnelli, 2001	continuation for 9 additional months; warfarin or acenocoumarol adjusted to achieve a target INR between 2.0 and 3.0	discontinuation (after 3 months months)	Patients with a first episode of idiopathic proximal deep venous thrombosis who had completed three months of oral anticoagulant therapy
Agnelli, 2003	continuation for 3 or 9 additionnal months of warfarin or other oral anticoagulant was adjusted to achieve a target INR between 2.0 and 3.0.	discontinuation (after 3 months)	patients who had had 3 months of oral anticoagulant therapy without experiencing recurrence or bleeding after a first episode of pulmonary embolism
PREVENT (Ridker), 2003	extension with low-intensity warfarin (target INR, 1.5 to 2.0)	placebo	Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months
ELAET (Kearon), 2004	continuation for 2 additionnal months of warfarin adjusted to achieve a target INR between 2.0 and 3.0.	discontinuation (after 1 months)
DURAC (Schulman), 1997	indefinite warfarin or dicoumarol adjusted for a target INR between 2.0 and 2.85	6 months warfarin or dicoumarol adjusted for a target INR between 2.0 and 2.85

Bemiparin

venous thrombosis, in all type of patients

Dalteparin

acute coronary syndrome, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	1.09 [0.72 1.65]	p=1.00	0	4473	3	FRISC (long term), FRIC prolonged treatment phase (LWMH vs PBO), FRISC (short term),
All cause death	1.09 [0.72 1.65]	p=1.00	0	4473	3	FRISC (long term), FRIC prolonged treatment phase (LWMH vs PBO), FRISC (short term),
Bleeding	no data
Bleeding	no data
In-hospital death	no data
Revascularization	0.87 [0.71 1.07]	p=1.00	0	4473	3	FRISC (long term), FRIC prolonged treatment phase (LWMH vs PBO), FRISC (short term),
Major bleeding	no data
Major bleeding	no data
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	0.67 [0.51 0.87]	p=0.04	0	4473	3	FRISC (long term), FRIC prolonged treatment phase (LWMH vs PBO), FRISC (short term),
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	1.12 [0.83 1.51]	p=1.00	0	1482	1	FRIC prolonged treatment phase (LWMH vs PBO),
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	0.77 [0.60 0.98]	p=0.04	0	4473	3	FRISC (long term), FRISC (short term), FRIC prolonged treatment phase (LWMH vs PBO),
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
FRISC (long term), 1996	dalteparin SC 120 IU per kg bodyweight [maximum 10 000 IU] twice daily for 6 days with 7500 IU once daily for 34-45 days +aspirin	matched placebo + aspirin	patients with unstable CAD (unstable angina or non-Q-wave myocardial infarction) within the previous 72 hours
FRIC prolonged treatment phase (LWMH vs PBO), 1997	dalteparin SC 120 i.u./kg twice-daily for 6 days followed by dalteparin 7500UI daily up to day 45 (+aspirin)	unfractionated heparin dose-adjusted intravenous infusion (for at least 48h) then by subcutaneous injection up to day 6 (then placebo) (+aspirin)	Patients with unstable angina or non-Q-wave myocardial infarction
FRISC (short term), 1996	dalteparin SC 120 IU per kg bodyweight [maximum 10 000 IU] twice daily for 6 days with 7500 IU once daily for 34-45 days +aspirin	matched placebo + aspirin	patients with unstable CAD (unstable angina or non-Q-wave myocardial infarction) within the previous 72 hours

Dalteparin

acute coronary syndrome, in all type of patients

Dalteparin

thrombosis prevention, in general surgery

Dalteparin

thrombosis prevention, in general surgery

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	1.26 [0.93 1.72]	p=1.00	0	5843	8	Onarheim, Koller, Koller, Bergqvist, Caen, Hartl, Borstad, Kakkar,
All cause death	1.26 [0.93 1.72]	p=1.00	0	5843	8	Onarheim, Koller, Koller, Bergqvist, Caen, Hartl, Borstad, Kakkar,
Bleeding	0.94 [0.80 1.11]	p=1.00	0	6570	11	Bergqvist, Onarheim, Koller, Koller, Fricker, Bergqvist, Caen, Borstad, Hartl, Borstad, Kakkar,
Bleeding	0.94 [0.80 1.11]	p=1.00	0	6570	11	Bergqvist, Onarheim, Koller, Koller, Fricker, Bergqvist, Caen, Borstad, Hartl, Borstad, Kakkar,
In-hospital death	no data
Revascularization	no data
Major bleeding	0.92 [0.70 1.22]	p=1.00	0	5568	10	Bergqvist, Onarheim, Koller, Koller, Fricker, Caen, Borstad, Hartl, Borstad, Kakkar,
Major bleeding	0.92 [0.70 1.22]	p=1.00	0	5568	10	Bergqvist, Onarheim, Koller, Koller, Fricker, Caen, Borstad, Hartl, Borstad, Kakkar,
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	no data
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	1.21 [0.66 2.22]	p=1.00	0	3961	2	Borstad, Kakkar,
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	no data
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	0.90 [0.63 1.29]	p=1.00	0	2764	10	Bergqvist, Onarheim, Koller, Fricker, Bergqvist, Caen, Borstad, Briel, Creperio, Hartl,
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	0.51 [0.33 0.79]	p=0.04	0	3961	2	Borstad, Kakkar,
Symptomatic venous thromboembolism (DVT, PE)	0.37 [0.07 2.10]	p=1.00	0	335	3	Fricker, Borstad, Creperio,
transfusion	1.09 [0.89 1.33]	p=1.00	0	2262	6	Bergqvist, Koller, Koller, Bergqvist, Caen, Hartl,
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	no data
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
Bergqvist, 1986	Dalteparin 5000	UFH 10 000 units	Abdominal surgery
Onarheim, 1986	Dalteparin 5000	UFH 10 000 units	Abdominal surgery
Koller, 1986	Dalteparin 7500	UFH 10 000 units	Abdominal surgery
Koller, 1986	Dalteparin 2500	UFH 10 000 units	Abdominal surgery
Fricker, 1988	Dalteparin 5000	UFH 15 000 units	Abdominopelvic surgery
Bergqvist, 1988	Dalteparin 5000	UFH 10 000 units	Abdominal surgery
Caen, 1988	Dalteparin 2500	UFH 10 000 units	Abdominal surgery
Borstad, 1988	Dalteparin 5000	UFH 10 000 units	Gynaecological surgery
Briel, 1988	Dalteparin 5000	UFH 10 000 units+DHE	Gynaecological surgery
Creperio, 1990	Dalteparin 2500	UFH 10 000 units	General surgery
Hartl, 1990	Dalteparin 2500	UFH 10 000 units	Abdominal surgery
Borstad, 1992	Dalteparin 2500 anti Xa units	UFH 10 000 units	Gynaecological surgery
Kakkar, 1993	Dalteparin 2500 anti Xa units	UFH 10 000 units	Abdominal surgery

Dalteparin

thrombosis prevention, in orthopedic surgery

Dalteparin

thrombosis prevention, in orthopedic surgery

Dalteparin

thrombosis prevention, in orthopedic surgery

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	0.58 [0.15 2.32]	p=1.00	0	428	4	Barre , Dechavanne , Eriksson , Monreal ,
All cause death	0.58 [0.15 2.32]	p=1.00	0	428	4	Barre , Dechavanne , Eriksson , Monreal ,
Bleeding	0.95 [0.36 2.52]	p=1.00	0	523	5	Binsack , Barre , Dechavanne , Eriksson , Monreal ,
Bleeding	0.95 [0.36 2.52]	p=1.00	0	523	5	Binsack , Barre , Dechavanne , Eriksson , Monreal ,
In-hospital death	no data
Revascularization	no data
Major bleeding	no data
Major bleeding	no data
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	no data
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	0.66 [0.29 1.51]	p=1.00	0	436	4	Haas , Barre , Eriksson , Monreal ,
Deep vein thrombosis	1.01 [0.65 1.56]	p=1.00	0	653	6	Haas , Binsack , Barre , Dechavanne , Eriksson , Monreal ,
reinfarction	no data
recurrent angina	no data
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	no data
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
Haas , 1985	dalteparin	Unfractionated heparin	Elective hip
Binsack , 1986	dalteparin	Unfractionated heparin	Elective hip
Barre , 1987	dalteparin	Unfractionated heparin	Elective hip
Dechavanne , 1989	dalteparin	Unfractionated heparin	Elective hip
Eriksson , 1989	dalteparin	Unfractionated heparin	Elective hip
Monreal , 1989	dalteparin	Unfractionated heparin	Hip

Dalteparin

venous thrombosis, in all type of patients

Dalteparin

venous thrombosis, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	1.38 [0.57 3.30]	p=1.00	0	434	4	Bratt et al , Holm et al , Bratt et al, Lindmarker et al ,
All cause death	1.38 [0.57 3.30]	p=1.00	0	434	4	Bratt et al , Holm et al , Bratt et al, Lindmarker et al ,
Bleeding	no data
Bleeding	no data
In-hospital death	no data
Revascularization	no data
Major bleeding	no data
Major bleeding	no data
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	no data
Recurrent thromboembolic event	1.21 [0.49 2.97]	p=1.00	0	434	4	Bratt et al , Holm et al , Bratt et al, Lindmarker et al ,
Thrombus extension	0.59 [0.25 1.43]	p=1.00	0	434	4	Bratt et al , Holm et al , Bratt et al, Lindmarker et al ,
Short term haemorrhage	1.17 [0.21 6.42]	p=1.00	0	434	4	Bratt et al , Holm et al , Bratt et al, Lindmarker et al ,
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	no data
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	no data
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control
Bratt et al , 1985	Dalteparin Intravenousv (ajusted) for >=5 Days, 120 U/kg BID	unfractionated heparin intravenous APPTx1.7-3.5
Holm et al , 1986	Dalteparin Subcutaneous twice daily ajusted for 7 Days, 57-107 U/kg BID	unfractionated heparin subcutaneous twice daily 16000-30000 U
Bratt et al, 1990	Dalteparin Subcutaneous twice daily ajusted for >= 5 Days, 120 U/kg BID	unfractionated heparin intravenous APPTx2-4
Lindmarker et al , 1993	Dalteparin Subcutaneous once daily for >= 5 Days, 200 U/kg BID	unfractionated heparin intravenous APPTx1.5-3

Dalteparin

venous thrombosis, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	2.53 [0.26 24.90]	p=1.00	0	140	1	Partsch,
All cause death	2.53 [0.26 24.90]	p=1.00	0	140	1	Partsch,
Bleeding	0.95 [0.10 9.31]	p=1.00	0	227	2	Holmström, Partsch,
Bleeding	0.95 [0.10 9.31]	p=1.00	0	227	2	Holmström, Partsch,
In-hospital death	no data
Revascularization	no data
Major bleeding	no data
Major bleeding	no data
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	no data
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	no data
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	no data
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
Holmström, 1992	once daily dalteparin 200 U (anti-FXa)/kg for at least 5 days	twice daily dalteparin 100 U (anti-FXa)/kg for at least 5 days	Patients with a first occurence of DVT in the lower limb, confirmed with phlebographytio
Partsch, 1996	Fragmin administered 200 IU/kg once daily for at least 7 days	Fragmin 100 IU/kg twice daily for at least 7 days	patients presented with DVT extending into the iliofemoral segment diagnosed by duplex ultrasonographyA

Ardeparin

thrombosis prevention, in orthopedic surgery

Ardeparin

thrombosis prevention, in general surgery

Certoparin

thrombosis prevention, in orthopedic surgery

Certoparin

thrombosis prevention, in general surgery

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	1.07 [0.86 1.32]	p=1.00	0	24981	8	Sasahara, Voigt, Baumgartner, Koppenhagen, Schielke, Koppenhagen, Heilmann, Haas,
All cause death	1.07 [0.86 1.32]	p=1.00	0	24981	8	Sasahara, Voigt, Baumgartner, Koppenhagen, Schielke, Koppenhagen, Heilmann, Haas,
Bleeding	0.58 [0.39 0.87]	p=0.04	0	737	3	Voigt, Kakkar, Heilmann,
Bleeding	0.58 [0.39 0.87]	p=0.04	0	737	3	Voigt, Kakkar, Heilmann,
In-hospital death	no data
Revascularization	no data
Major bleeding	0.84 [0.58 1.23]	p=1.00	0	3076	10	Schmitz-Huebner, Voigt, Kakkar, Heilmann, Baumgartner, Hoffmann and Largiade, Koppenhagen, Schielke, Hoffmann and Largiader, Heilmann,
Major bleeding	0.84 [0.58 1.23]	p=1.00	0	3076	10	Schmitz-Huebner, Voigt, Kakkar, Heilmann, Baumgartner, Hoffmann and Largiade, Koppenhagen, Schielke, Hoffmann and Largiader, Heilmann,
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	no data
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	0.97 [0.56 1.68]	p=1.00	0	24801	5	Schielke, Koppenhagen, Hoffmann and Largiader, Heilmann, Haas,
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	no data
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	0.86 [0.63 1.17]	p=1.00	0	2921	11	Schmitz-Huebner, Sasahara, Voigt, Welzel, Kakkar, Adolf, Heilmann, Baumgartner, Koppenhagen, Koppenhagen, Heilmann,
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	2.79 [0.25 30.92]	p=1.00	0	777	2	Koppenhagen, Koppenhagen,
Symptomatic venous thromboembolism (DVT, PE)	0.27 [0.02 3.03]	p=1.00	0	326	2	Schmitz-Huebner, Voigt,
transfusion	0.98 [0.72 1.33]	p=1.00	0	879	3	Sasahara, Voigt, Adolf,
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	no data
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
Schmitz-Huebner, 1984	Certoparin (dose 1 and dose 2) b.i.d.	UFH 10 000 units	Abdominal surgery
Sasahara, 1986	Certoparin 3000 + DHE	UFH 10 000 units +DHE	Abdominal surgery
Voigt, 1986	Certoparin 3000 + DHE	UFH 10 000 units	Abdominal surgery
Welzel, 1988	Certoparin 2500 + DHE	UFH 10 000 units+DHE	Abdominal surgery
Kakkar, 1989	Certoparin 3000 + DHE	UFH 10 000 units+DHE	Abdominal surgery
Adolf, 1989	Certoparin 3000	UFH 15 000 units	Abdominal surgery
Heilmann, 1989	Certoparin 3000	UFH 15 000 units	Gynaecological surgery
Baumgartner, 1989	Certoparin 3000 + DHE	UFH 5 000 units+DHE	Abdominal surgery
Hoffmann and Largiade, 1990	Certoparin 3000 + DHE	UFH 10 000 units	Abdominal surgery
Koppenhagen, 1990	Certoparin 3000 anti Xa units	UFH 15 000 units	Abdominal surgery
Schielke, 1991	Certoparin 3000 anti Xa units + DHE	UFH 10 000 units + DHE	Abdominal surgery
Koppenhagen, 1992	Certoparin 3000 anti Xa units	UFH 15 000 units	Abdominal surgery
Hoffmann and Largiader, 1992	Certoparin 3000 anti Xa units	UFH 10 000 units	Abdominothoracic surgery
Heilmann, 1997	Certoparin 3000 anti Xa units	UFH 15 000 units	Gynaecological and breast surgery
Haas, 1999	Certoparin 3000 anti Xa units	UFH 15 000 units	General surgery

Fraxiparin

thrombosis prevention, in general surgery

Fraxiparin

thrombosis prevention, in orthopedic surgery

Reviparin

thrombosis prevention, in general surgery

Tinzaparin

thrombosis prevention, in orthopedic surgery

Tinzaparin

thrombosis prevention, in general surgery

Tinzaparin

thrombosis prevention, in general surgery

Tinzaparin

venous thrombosis, in all type of patients

Tinzaparin

venous thrombosis, in all type of patients

Tinzaparin

venous thrombosis, in all type of patients

Logiparin

venous thrombosis, in all type of patients

Enoxaparin

acute coronary syndrome, in all type of patients

Enoxaparin

acute coronary syndrome, in all type of patients

Enoxaparin

acute coronary syndrome, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	0.97 [0.83 1.13]	p=1.00	0	21715	5	ESSENCE, TIMI 11 B (short term), SYNERGY, INTERACT, TIMI 11 B (long term),
All cause death	0.97 [0.83 1.13]	p=1.00	0	21715	5	ESSENCE, TIMI 11 B (short term), SYNERGY, INTERACT, TIMI 11 B (long term),
Bleeding	no data
Bleeding	no data
In-hospital death	no data
Revascularization	0.86 [0.78 0.96]	p=0.04	0	11737	4	ESSENCE, TIMI 11 B (short term), INTERACT, TIMI 11 B (long term),
Major bleeding	1.15 [1.02 1.30]	p=0.04	0	20132	5	ESSENCE, TIMI 11 B (short term), SYNERGY, INTERACT, TIMI 11 B (long term),
Major bleeding	1.15 [1.02 1.30]	p=0.04	0	20132	5	ESSENCE, TIMI 11 B (short term), SYNERGY, INTERACT, TIMI 11 B (long term),
Minor bleeding	1.40 [1.28 1.53]	p=0.04	0	20133	5	ESSENCE, TIMI 11 B (short term), SYNERGY, INTERACT, TIMI 11 B (long term),
Minor bleeding	1.40 [1.28 1.53]	p=0.04	0	20133	5	ESSENCE, TIMI 11 B (short term), SYNERGY, INTERACT, TIMI 11 B (long term),
Deaths or MI	no data
stroke (fatal and non fatal)	0.97 [0.34 2.78]	p=1.00	0	3171	1	ESSENCE,
myocardial infarction (fatal and non fatal)	0.88 [0.79 0.97]	p=0.04	0	21715	5	ESSENCE, TIMI 11 B (short term), SYNERGY, INTERACT, TIMI 11 B (long term),
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	0.81 [0.66 0.98]	p=0.04	0	3917	2	ESSENCE, INTERACT,
Drop in platelet count of 50%	0.68 [0.45 1.03]	p=1.00	0	3171	1	ESSENCE,
death, myocardial infarction, or recurrent at 14 days	0.84 [0.70 1.00]	p=1.00	0	3171	1	ESSENCE,
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	0.91 [0.83 1.00]	p=1.00	0	21715	5	ESSENCE, TIMI 11 B (short term), SYNERGY, INTERACT, TIMI 11 B (long term),
death, myocardial infarction, or recurrent at 30 days	0.83 [0.71 0.98]	p=0.04	0	3917	2	ESSENCE, INTERACT,
death at 30 days	0.95 [0.78 1.15]	p=1.00	0	13895	3	ESSENCE, SYNERGY, INTERACT,
myocardial infarction at 30 days	0.89 [0.80 1.00]	p=1.00	0	13895	3	ESSENCE, SYNERGY, INTERACT,
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
ESSENCE, 1997	enoxaparin 1mg/kg, twice daily during 48h-8days	continuous intravenous unfractionated heparin	patients with angina at rest or non–Q-wave myocardial infarction
TIMI 11 B (short term), 1998	enoxaprin during both the acute phase and outpatient phase	intravenous UFH for >=3 days (followed by subcutaneous placebo injections)	unstable angina/non–Q-wave myocardial infarction
SYNERGY, 2005	Enoxaparin 1 mg/kg twice daily	unfractionated heparin	high-risk patients with acute coronary syndromes
INTERACT, 2006	enoxaparin (1 mg/kg subcutaneously twice daily) for 48 hours (+eptifibatide and aspirin)	intravenous UFH (70 U/kg bolus followed by 15 U/kg per hour adjusted to an activated partial thromboplastin time of 1.5-2 times control) for 48 hours (+eptifibatide and aspirin)	high-risk patients with ACS receiving aspirin and eptifibatide
TIMI 11 B (long term), 1998	enoxaprin during both the acute phase (IV) and outpatient phase (SC)	intravenous UFH for >=3 days (followed by subcutaneous placebo injections)	unstable angina/non–Q-wave myocardial infarction

Enoxaparin

acute myocardial infarction, in patients eligible to receive fibrinolytic therapy

Enoxaparin

thrombosis prevention, in orthopedic surgery

Enoxaparin

thrombosis prevention, in orthopedic surgery

Enoxaparin

thrombosis prevention, in orthopedic surgery

Enoxaparin

thrombosis prevention, in orthopedic surgery

Enoxaparin

thrombosis prevention, in general surgery

Enoxaparin

thrombosis prevention, in general surgery

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	0.75 [0.49 1.17]	p=1.00	0	4766	7	Samama 1, Samama 2, Samama 3, Gazzaniga (ISG), Nurmohamed, Gonzalez, ENOXACAN,
All cause death	0.75 [0.49 1.17]	p=1.00	0	4766	7	Samama 1, Samama 2, Samama 3, Gazzaniga (ISG), Nurmohamed, Gonzalez, ENOXACAN,
Bleeding	0.94 [0.80 1.10]	p=1.00	0	6183	9	Samama 1, Samama 2, Samama 3, Kaaja, Gazzaniga (ISG), Nurmohamed, McLeod (Canadian), Gonzalez, ENOXACAN,
Bleeding	0.94 [0.80 1.10]	p=1.00	0	6183	9	Samama 1, Samama 2, Samama 3, Kaaja, Gazzaniga (ISG), Nurmohamed, McLeod (Canadian), Gonzalez, ENOXACAN,
In-hospital death	no data
Revascularization	no data
Major bleeding	1.03 [0.72 1.47]	p=1.00	0	6183	9	Samama 1, Samama 2, Samama 3, Kaaja, Gazzaniga (ISG), Nurmohamed, McLeod (Canadian), Gonzalez, ENOXACAN,
Major bleeding	1.03 [0.72 1.47]	p=1.00	0	6183	9	Samama 1, Samama 2, Samama 3, Kaaja, Gazzaniga (ISG), Nurmohamed, McLeod (Canadian), Gonzalez, ENOXACAN,
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	no data
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	0.68 [0.22 2.06]	p=1.00	0	3942	5	Kaaja, Gazzaniga (ISG), Nurmohamed, Gonzalez, ENOXACAN,
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	no data
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	0.97 [0.76 1.24]	p=1.00	0	5085	8	Samama 1, Samama 2, Samama 3, Gazzaniga (ISG), Nurmohamed, McLeod (Canadian), Gonzalez, ENOXACAN,
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	0.66 [0.24 1.79]	p=1.00	0	68	1	Kaaja,
Symptomatic venous thromboembolism (DVT, PE)	0.58 [0.11 2.96]	p=1.00	0	892	3	Samama 1, Samama 2, Samama 3,
transfusion	1.08 [0.83 1.41]	p=1.00	0	892	3	Samama 1, Samama 2, Samama 3,
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	no data
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
Samama 1, 1988	Enoxaparin 2000	UFH 15 000 units	General surgery
Samama 2, 1988	Enoxaparin 4000	UFH 15 000 units	General surgery
Samama 3, 1988	Enoxaparin 6000	UFH 15 000 units	General surgery
Kaaja, 1992	Enoxaparin 2000 anti Xa units	UFH 10 000 units	Gynaecological surgery
Gazzaniga (ISG), 1993	Enoxaparin 2000 anti Xa units	UFH 10 000 units	General and vascular surgery
Nurmohamed, 1995	Enoxaparin 2000 anti Xa units	UFH 15 000 units	General surgery
McLeod (Canadian), 1995	Enoxaparin 4000 anti Xa units	UFH 15 000 units	Colorectal surgery
Gonzalez, 1996	Bemiparin 2500 anti Xa units	UFH 10 000 units	Abdominal surgery
ENOXACAN, 1997	Enoxaparin 4000 anti Xa units	UFH 15 000 units	Abdominopelvic surgery

Enoxaparin

thrombosis prevention, in neurosurgery

Enoxaparin

venous thrombosis, in all type of patients

Enoxaparin

venous thrombosis, in all type of patients

Enoxaparin

venous thrombosis, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	no data
All cause death	no data
Bleeding	no data
Bleeding	no data
In-hospital death	no data
Revascularization	no data
Major bleeding	no data
Major bleeding	no data
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	no data
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	no data
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	2.91 [0.96 8.85]	p=1.00	0	299	2	Pini, Meyer,
VTE during active anticoagulant treatment	0.62 [0.31 1.24]	p=1.00	0	453	3	Pini, Gonzalez-Fajardo, Deitcher,
myocardial infarction or death	no data
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
Pini, 1994	UFH, APTT 1.3–1.9 followed by Enoxaparin 4,000 IU qd	UFH, APTT 1.3–1.9 followed by Warfarin target INR 2-3.5	patients with objective diagnosis of DVT by Venography (diagnosed by strain-gauge plethysmography plus D-dimer latex assay and confirmed by venography)
Gonzalez-Fajardo, 1999	LMWH, 4,000 IU bid followed by Enoxaparin 4,000 IU qd	UFH followed by Warfarin target INR 2-3	patients with objective diagnosis of DVT by Venography
Meyer, 2002	LMWH, 1.5 mg/kg qd followed by Enoxaparin 1.5 mg/Kg qd	LMWH, 1.5 mg/kg qd followed by Warfarin target INR 2-3	patients with cancer and objective diagnosis of DVT by Venography/compression ultrasonography
Deitcher, 2003	LMWH: 1a, 1 mg/kg q12h; 1b, 1 mg/kg qd12h followed by Enoxaparin 1a: 1 mg/kg qd; 1b: 1.5 mg/kg qd	LMWH, 1 mg/kg q12h followed by Warfarin target INR 2-3	patients with objective diagnosis of DVT

Enoxaparin

venous thrombosis, in all type of patients

Enoxaparin

venous thrombosis, in all type of patients

Enoxaparin

venous thrombosis, in all type of patients

Nadroparin

acute coronary syndrome, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	1.18 [0.74 1.88]	p=1.00	0	4619	2	FRAXIS (6days), FRAXIS (14 days),
All cause death	1.18 [0.74 1.88]	p=1.00	0	4619	2	FRAXIS (6days), FRAXIS (14 days),
Bleeding	no data
Bleeding	no data
In-hospital death	no data
Revascularization	0.95 [0.78 1.15]	p=1.00	0	4619	2	FRAXIS (6days), FRAXIS (14 days),
Major bleeding	no data
Major bleeding	no data
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	1.02 [0.73 1.43]	p=1.00	0	4619	2	FRAXIS (6days), FRAXIS (14 days),
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	0.99 [0.83 1.17]	p=1.00	0	4619	2	FRAXIS (6days), FRAXIS (14 days),
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	0.99 [0.80 1.22]	p=1.00	0	2317	1	FRAXIS (6days),
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	1.04 [0.77 1.40]	p=1.00	0	4619	2	FRAXIS (6days), FRAXIS (14 days),
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	1.18 [0.77 1.80]	p=1.00	0	2317	1	FRAXIS (6days),
myocardial infarction at 30 days	1.10 [0.77 1.55]	p=1.00	0	2317	1	FRAXIS (6days),
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
FRAXIS (6days), 1998	nadroparin for 6 days (+aspirin)	unfractionated heparin for 6 days (+aspirin)	unstable angina or non-Q wave myocardial infraction
FRAXIS (14 days), 1998	nadroparin for 14 days	unfractionated heparin for 14 days	unstable angina or non-Q wave myocardial infraction

Nadroparin

thrombosis prevention, in orthopedic surgery

Nadroparin

thrombosis prevention, in orthopedic surgery

Nadroparin

thrombosis prevention, in general surgery

Nadroparin

thrombosis prevention, in general surgery

Nadroparin

thrombosis prevention, in general surgery

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	0.87 [0.44 1.72]	p=1.00	0	2309	2	Kakkar and Murray, EFS,
All cause death	0.87 [0.44 1.72]	p=1.00	0	2309	2	Kakkar and Murray, EFS,
Bleeding	1.00 [0.81 1.24]	p=1.00	0	2389	2	EFS, Eurin,
Bleeding	1.00 [0.81 1.24]	p=1.00	0	2389	2	EFS, Eurin,
In-hospital death	no data
Revascularization	no data
Major bleeding	2.98 [0.12 73.40]	p=1.00	0	480	1	Eurin,
Major bleeding	2.98 [0.12 73.40]	p=1.00	0	480	1	Eurin,
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	no data
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	0.20 [0.01 4.25]	p=1.00	0	344	1	Barbui,
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	no data
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	0.61 [0.40 0.93]	p=0.04	0	2917	5	Kakkar and Murray, EFS, Dahan, Barbui, Eurin,
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	1.12 [0.45 2.84]	p=1.00	0	344	1	Barbui,
Symptomatic venous thromboembolism (DVT, PE)	0.25 [0.08 0.83]	p=0.04	0	2309	2	Kakkar and Murray, EFS,
transfusion	1.04 [0.84 1.29]	p=1.00	0	2309	2	Kakkar and Murray, EFS,
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	no data
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
Kakkar and Murray, 1985	Nadroparin 2850	UFH 10 000 units	General surgery
EFS, 1988	Nadroparin 2850	UFH 15 000 units	Abdominal surgery
Dahan, 1989	Nadroparin 2850	UFH 15 000 units	Thoracic surgery
Barbui, 1990	Nadroparin 2850 anti Xa units	UFH 10 000 units	General surgery
Eurin, 1994	Nadroparin 2850 anti Xa units	UFH 15 000 units	Abdominopelvic surgery

Nadroparin

thrombosis prevention, in neurosurgery

Nadroparin

venous thrombosis, in all type of patients

Nadroparin

venous thrombosis, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	0.58 [0.24 1.45]	p=1.00	0	455	3	Collaborative European Multicentre, Prandoni et al , Lopaciuk et al ,
All cause death	0.58 [0.24 1.45]	p=1.00	0	455	3	Collaborative European Multicentre, Prandoni et al , Lopaciuk et al ,
Bleeding	no data
Bleeding	no data
In-hospital death	no data
Revascularization	no data
Major bleeding	no data
Major bleeding	no data
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	no data
Recurrent thromboembolic event	0.58 [0.24 1.43]	p=1.00	0	455	3	Collaborative European Multicentre, Prandoni et al , Lopaciuk et al ,
Thrombus extension	0.57 [0.30 1.09]	p=1.00	0	455	3	Collaborative European Multicentre, Prandoni et al , Lopaciuk et al ,
Short term haemorrhage	0.85 [0.24 3.01]	p=1.00	0	455	3	Collaborative European Multicentre, Prandoni et al , Lopaciuk et al ,
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	no data
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	no data
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control
Collaborative European Multicentre, 1991	Nadroparin Subcutaneous twice daily for 10 Days, 90 U/kg BID	unfractionated heparin intravenous APPTx1.5-2
Prandoni et al , 1992	Nadroparin Subcutaneous twice daily for >=0 Days, 90 U/kg BID	unfractionated heparin intravenous APPTx1.5-2
Lopaciuk et al , 1992	Nadroparin Subcutaneous twice daily for 10 Days, 92 U/kg BID	unfractionated heparin subcutaneous twice daily APPTx1.5-2.5

Nadroparin

venous thrombosis, in all type of patients

UFH

acute coronary syndrome, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	1.00 [0.20 5.01]	p=1.00	0	526	3	ATACS (Cohen), Cohen (ATACS pilot) (heparin+aspirin vs asp), Theroux (heparin+ASP vs ASP),
All cause death	1.00 [0.20 5.01]	p=1.00	0	526	3	ATACS (Cohen), Cohen (ATACS pilot) (heparin+aspirin vs asp), Theroux (heparin+ASP vs ASP),
Bleeding	no data
Bleeding	no data
In-hospital death	no data
Revascularization	1.59 [0.60 4.19]	p=1.00	0	69	1	Cohen (ATACS pilot) (heparin+aspirin vs asp),
Major bleeding	1.84 [0.56 6.03]	p=1.00	0	811	4	ATACS (Cohen), Holdright, Cohen (ATACS pilot) (heparin+aspirin vs asp), Theroux (heparin+ASP vs ASP),
Major bleeding	1.84 [0.56 6.03]	p=1.00	0	811	4	ATACS (Cohen), Holdright, Cohen (ATACS pilot) (heparin+aspirin vs asp), Theroux (heparin+ASP vs ASP),
Minor bleeding	0.86 [0.05 14.41]	p=1.00	0	69	1	Cohen (ATACS pilot) (heparin+aspirin vs asp),
Minor bleeding	0.86 [0.05 14.41]	p=1.00	0	69	1	Cohen (ATACS pilot) (heparin+aspirin vs asp),
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	0.60 [0.25 1.43]	p=1.00	0	526	3	ATACS (Cohen), Cohen (ATACS pilot) (heparin+aspirin vs asp), Theroux (heparin+ASP vs ASP),
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	0.74 [0.47 1.19]	p=1.00	0	526	3	ATACS (Cohen), Cohen (ATACS pilot) (heparin+aspirin vs asp), Theroux (heparin+ASP vs ASP),
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	0.78 [0.52 1.18]	p=1.00	0	1141	4	ATACS (Cohen), Holdright, RISC (heparin+aspirin vs ASP), Theroux (heparin+ASP vs ASP),
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
ATACS (Cohen), 1994	aspirin 162.5 mg daily plus heparin (activated partial thromboplastin time, two times control) followed by aspirin 162.5 mg daily plus warfarin (international normalized ratio, 2 to 3) for 12 weeks.	aspirin alone (162.5 mg daily) for 12 weeks.	patients with unstable rest angina or non-Q-wave myocardial infarction with last episode of pain within 48 hours of randomization and who were nonprior aspirin users
Holdright, 1994	intravenous heparin plus oral aspirin (150 mg once daily)	aspirin alone 150 mg/d	unstable angina
Cohen (ATACS pilot) (heparin+aspirin vs asp), 1990	aspirin (80 mg/day) plus heparin and then warfarin	aspirin (325 mg/day)	Patients between 21 and 75 years with unstable angina or non-Q-wave MI with last episode of pain within 48 hours of screening.
RISC (heparin+aspirin vs ASP), 1990	5 days of intermittent intravenous heparin + oral aspirin 75 mg/day	oral aspirin 75 mg/day	unstable angina or non-Q-wave myocardial infarction
Theroux (heparin+ASP vs ASP), 1988	aspirin 325 mg/d + heparin 1000 UI/hr IV	aspirin 325 mg/d

UFH

acute coronary syndrome, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	0.20 [0.02 1.70]	p=1.00	0	476	2	Theroux (heparin+aspirin vs PBO), Theroux (heparin vs PBO),
All cause death	0.20 [0.02 1.70]	p=1.00	0	476	2	Theroux (heparin+aspirin vs PBO), Theroux (heparin vs PBO),
Bleeding	no data
Bleeding	no data
In-hospital death	no data
Revascularization	no data
Major bleeding	1.53 [0.46 5.14]	p=1.00	0	476	2	Theroux (heparin+aspirin vs PBO), Theroux (heparin vs PBO),
Major bleeding	1.53 [0.46 5.14]	p=1.00	0	476	2	Theroux (heparin+aspirin vs PBO), Theroux (heparin vs PBO),
Minor bleeding	2.00 [0.59 6.83]	p=1.00	0	236	1	Theroux (heparin vs PBO),
Minor bleeding	2.00 [0.59 6.83]	p=1.00	0	236	1	Theroux (heparin vs PBO),
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	0.11 [0.03 0.37]	p=0.04	0	476	2	Theroux (heparin+aspirin vs PBO), Theroux (heparin vs PBO),
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	0.42 [0.25 0.71]	p=0.04	0	476	2	Theroux (heparin+aspirin vs PBO), Theroux (heparin vs PBO),
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	0.53 [0.33 0.86]	p=0.04	0	1281	4	Theroux (heparin+aspirin vs PBO), Theroux (heparin vs PBO), RISC (heparin vs PBO), RISC (ASP+ heparin vs PBO),
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
Theroux (heparin+aspirin vs PBO), 1988	heparin (1000 units per hour by intravenous infusion)+ aspirin (325 mg twice daily)	aspirin (325 mg twice daily)
Theroux (heparin vs PBO), 1988	heparin (1000 units per hour by intravenous infusion)	placebo	patients with acute unstable angina pectoris
RISC (heparin vs PBO), 1990	5 days of intermittent intravenous heparin	placebo	men with unstable coronary artery disease (unstable angina or non-Q-wave myocardial infarction)
RISC (ASP+ heparin vs PBO), 1990	oral apsirin 75mg/d + intermittent IV heparin 10000UI/d followed by 7500 UI 6-hourly for 4 days	placebo	men with unstable coronary artery disease (unstable angina or non-Q-wave myocardial infarction)

UFH

acute coronary syndrome, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	1.04 [0.02 53.29]	p=1.00	0	143	1	Gurfinkel (UFH+aspririn vs aspirin),
All cause death	1.04 [0.02 53.29]	p=1.00	0	143	1	Gurfinkel (UFH+aspririn vs aspirin),
Bleeding	no data
Bleeding	no data
In-hospital death	no data
Revascularization	0.81 [0.28 2.31]	p=1.00	0	143	1	Gurfinkel (UFH+aspririn vs aspirin),
Major bleeding	5.21 [0.29 92.25]	p=1.00	0	143	1	Gurfinkel (UFH+aspririn vs aspirin),
Major bleeding	5.21 [0.29 92.25]	p=1.00	0	143	1	Gurfinkel (UFH+aspririn vs aspirin),
Minor bleeding	21.90 [1.26 381.54]	p=0.04	0	143	1	Gurfinkel (UFH+aspririn vs aspirin),
Minor bleeding	21.90 [1.26 381.54]	p=0.04	0	143	1	Gurfinkel (UFH+aspririn vs aspirin),
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	0.60 [0.17 2.13]	p=1.00	0	143	1	Gurfinkel (UFH+aspririn vs aspirin),
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	1.20 [0.61 2.34]	p=1.00	0	143	1	Gurfinkel (UFH+aspririn vs aspirin),
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	0.60 [0.17 2.13]	p=1.00	0	143	1	Gurfinkel (UFH+aspririn vs aspirin),
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
Gurfinkel (UFH+aspririn vs aspirin), 1995	aspirin plus UFH 5000 IU iv then 400 IU/kg body weight per day intravenously and titered by activated partial thromboplastin time	aspirin 200 mg/day	patients greater than 21 years with ustable angina within 24 hours of randomizationcatio

UFH

acute coronary syndrome, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	1.33 [0.03 69.68]	p=1.00	0	56	1	Cohen (ATACS pilot) (heparin vs asp),
All cause death	1.33 [0.03 69.68]	p=1.00	0	56	1	Cohen (ATACS pilot) (heparin vs asp),
Bleeding	no data
Bleeding	no data
In-hospital death	no data
Revascularization	1.33 [0.46 3.90]	p=1.00	0	56	1	Cohen (ATACS pilot) (heparin vs asp),
Major bleeding	1.33 [0.03 69.68]	p=1.00	0	56	1	Cohen (ATACS pilot) (heparin vs asp),
Major bleeding	1.33 [0.03 69.68]	p=1.00	0	56	1	Cohen (ATACS pilot) (heparin vs asp),
Minor bleeding	0.44 [0.02 11.41]	p=1.00	0	56	1	Cohen (ATACS pilot) (heparin vs asp),
Minor bleeding	0.44 [0.02 11.41]	p=1.00	0	56	1	Cohen (ATACS pilot) (heparin vs asp),
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	no data
Recurrent thromboembolic event	no data
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	0.83 [0.29 2.42]	p=1.00	0	56	1	Cohen (ATACS pilot) (heparin vs asp),
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	4.00 [0.39 41.11]	p=1.00	0	56	1	Cohen (ATACS pilot) (heparin vs asp),
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control	Patients
Cohen (ATACS pilot) (heparin vs asp), 1990	heparin followed by warfarin (without aspirin)	aspirin 325 mg/day	Patients between 21 and 75 years with unstable angina or non-Q-wave MI with last episode of pain within 48 hours of screening

UFH

acute myocardial infarction, in patients eligible to receive fibrinolytic therapy

UFH

acute myocardial infarction, in patients eligible to receive fibrinolytic therapy

UFH

thrombosis prevention, in neurosurgery

Heparin

venous thrombosis, in all type of patients

Endpoint	TE [95% CI]	p val	I2	n	k	trials
All cause death	no data
All cause death	no data
Bleeding	no data
Bleeding	no data
In-hospital death	no data
Revascularization	no data
Major bleeding	0.81 [0.40 1.64]	p=1.00	0	783	6	Bentley, Hull, Doyle, Walker, Lopaciuk, Pini,
Major bleeding	0.81 [0.40 1.64]	p=1.00	0	783	6	Bentley, Hull, Doyle, Walker, Lopaciuk, Pini,
Minor bleeding	no data
Minor bleeding	no data
Deaths or MI	no data
stroke (fatal and non fatal)	no data
myocardial infarction (fatal and non fatal)	no data
Recurrent thromboembolic event	0.72 [0.38 1.36]	p=1.00	0	783	6	Bentley, Hull, Doyle, Walker, Lopaciuk, Pini,
Thrombus extension	no data
Short term haemorrhage	no data
Symptomatic pulmonary embolism	no data
Deep vein thrombosis	no data
reinfarction	no data
recurrent angina	no data
Drop in platelet count of 50%	no data
death, myocardial infarction, or recurrent at 14 days	no data
asymptomatic DVT	no data
total VTE and all-cause mortality	no data
asymptomatic proximal DVT	no data
wound haematoma / infection	no data
Symptomatic venous thromboembolism (DVT, PE)	no data
transfusion	no data
reinfarction at 30 days	no data
death at 30 days	no data
VTE during follow-up after active anticoagulant treatment	no data
VTE during active anticoagulant treatment	no data
myocardial infarction or death	no data
death, myocardial infarction, or recurrent at 30 days	no data
death at 30 days	no data
myocardial infarction at 30 days	no data
puylmonary embolism	no data
recurrent DVT	no data
major or clinically relevant non-major bleeding	no data
VTE	no data

TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients

Trial	Studied treatment	Control
Krahenbuhl, 1979	subcutaneous sodic heparin 30 000 U daily (mean)	intravenous sodic heparin 30 000 U daily (mean)
Bentley, 1980	subcutaneous calcic heparin 37 000 U daily (mean)	intravenous sodic heparin 36 800 U daily (mean)
Andersson, 1982	subcutaneous sodic heparin 36 800 U daily (mean)	intravenous sodic heparin 33 250 U daily (mean)
Hull, 1986	subcutaneous sodic heparin 32 300 U daily (mean)	intravenous sodic heparin 29 700 U daily (mean)
Doyle, 1987	subcutaneous calcic heparin 29 200 U daily (mean)	intravenous calcic heparin 29 600 U daily (mean)
Walker, 1987	subcutaneous calcic heparin 29 375 U daily (mean)	intravenous calcic heparin 24 384 U daily (mean)
Lopaciuk, 3000	subcutaneous sodic heparin 34 400 U daily (mean)	intravenous sodic heparin 37 000 U daily (mean)
Pini, 1990	subcutaneous calcic heparin 33 800 U daily (mean)	intravenous sodic heparin 31 700 U daily (mean)

heparin (UFH or LMWH)