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antithrombotics in venous thrombosis for all type of patients, clinical trials results

3-6 months versus 1.5-3 months
Pinede, 2001
Long course of therapy (6 months for proximal DVT and/or PE; 12 weeks for calf DVT) by fluindione adjusted for INR range of 2.0 to 3.0
versus
Short oral anticoagulant course (3 months for proximal DVT and/or PE; 6 weeks for isolated calf DVT) by fluindione adjusted for INR range of 2.0 to 3.0
open
Follow-up duration: 15 months after randomizationÛ
France
6 months versus 1.5 months
Schulman, 1995
6 months treatment with warfarin or dicoumarol adjusted for a target INR between 2.0 - 2.85
versus
1.5 months warfarin or dicoumarol adjusted for a target INR between 2.0 - 2.85
open
Follow-up duration: Two years after randomization
Sweden
apixaban (without LMWH) versus LMWH/VKA
AMPLIFY, 2013
NCT00643201
apixaban 10 mg twice daily for 7 days then 5 mg, twice daily, 6 months
versus
conventional therapy: enoxaparin 1mg/kg twice daily until INR>=2 then warfarin for an INR between 2-4, once daikly, 6 months
patients with deep vein thrombosis or pulmonary embolism double blind
Follow-up duration: 6 mo
Botticelli DVT, 2008
NCT00252005
apixaban 5 mg twice-daily, 10 mg twice-daily, or 20 mg once-daily for 84-91 days
versus
low molecular weight heparin followed by vitamin K antagonists
patients with symptomatic deep vein thrombosis open
apixaban 2.5mg versus discontinuation
AMPLIFY-EXT 2.5mg, 2012
NCT00633893
Extended Treatment with apixaban 2.5 mg twice daily 12 months
versus
placebo
patients who have completed their intended treatment for deep vein thrombosis or pulmonary embolism double blind
Follow-up duration: 12 mo
apixaban 5mg versus discontinuation
AMPLIFY-EXT 5mg, 2012
NCT00633893
Extended Treatment with apixaban 5 mg twice daily 12 months
versus
placebo
patients who have completed their intended treatment for deep vein thrombosis or pulmonary embolism double blind
Follow-up duration: 12 mo
Bemiparin versus warfarin
Kakkar, 2003
LMWH, 115 IU/kg qd followed by Bemiparin 3,500 IU qd
versus
A: UFH, 30/40,000IU qd; B: LMWH, 115 IU/kg qd followed by Warfarin target INR 2-3
patients with objective diagnosis of DVT by Venography/compression ultrasonographyopen
Follow-up duration: 3 mo
Dalteparin versus unfractionated heparin
Holm et al , 1986
Dalteparin Subcutaneous twice daily ajusted for 7 Days, 57-107 U/kg BID
versus
unfractionated heparin subcutaneous twice daily 16000-30000 U

Follow-up duration: Hospital Stay
Bratt et al , 1985
Dalteparin Intravenousv (ajusted) for >=5 Days, 120 U/kg BID
versus
unfractionated heparin intravenous APPTx1.7-3.5

Follow-up duration: 23 Months (mean)
Bratt et al, 1990
Dalteparin Subcutaneous twice daily ajusted for >= 5 Days, 120 U/kg BID
versus
unfractionated heparin intravenous APPTx2-4

Follow-up duration: Hospital stay
Lindmarker et al , 1993
Dalteparin Subcutaneous once daily for >= 5 Days, 200 U/kg BID
versus
unfractionated heparin intravenous APPTx1.5-3

Follow-up duration: 6 Months
Dalteparin versus warfarin
Lee, 2003
LMWH, 200 IU/kg qd followed by Dalteparin 150 IU/kg qd
versus
LMWH, 200 IU/kg qd followed by Warfarin target INR 2-3
patients with cancer and objective diagnosis of DVT by Venography/compression ultrasonographyopen
Follow-up duration: 6 mo
Das, 1996
UFH followed by Dalteparin 5,000 IU qd
versus
UFH followed by Warfarin target INR 2-3
patients with objective diagnosis of DVT by Venographyopen
Follow-up duration: 3 mo
Enoxaparin versus acenocoumarol
Veiga, 2000
UFH, APTT 1.5–2.0d followed by Enoxaparin 4,000 IU qd
versus
UFH, APTT 1.5–2.0d followed by Acenocoumarol target INR 2-3
patients with objective diagnosis of DVT by Venographyopen
Follow-up duration: 6-9 mo
Enoxaparin versus coumarin
González-Fajardo, 2008
long-term anticoagulant treatment with enoxaparin during at least 3 months
versus
long-term anticoagulant treatment with coumarin during at least 3 months
patients with symptomatic, unilateral, first-episode DVTopen, blind assessment
Follow-up duration: 1y, 5y
Spain
Enoxaparin versus unfractionated heparin
Simonneau et al , 1993
Enoxaparin Subcutaneous twice daily for 0 Days, 100 U/kg BID
versus
unfractionated heparin intravenous APPTx1.5-2.5

Follow-up duration: 3 Months
Enoxaparin versus warfarin
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
versus
LMWH, 1 mg/kg q12h followed by Warfarin target INR 2-3
patients with objective diagnosis of DVTopen
Follow-up duration: 6 mo
Meyer, 2002
LMWH, 1.5 mg/kg qd followed by Enoxaparin 1.5 mg/Kg qd
versus
LMWH, 1.5 mg/kg qd followed by Warfarin target INR 2-3
patients with cancer and objective diagnosis of DVT by Venography/compression ultrasonographyopen
Follow-up duration: 3 mo
Gonzalez-Fajardo, 1999
LMWH, 4,000 IU bid followed by Enoxaparin 4,000 IU qd
versus
UFH followed by Warfarin target INR 2-3
patients with objective diagnosis of DVT by Venographyopen
Follow-up duration: 9 mo
Pini, 1994
UFH, APTT 1.3–1.9 followed by Enoxaparin 4,000 IU qd
versus
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)open
Follow-up duration: 9 mo
fondaparinux versus enoxaparin
MATISSE, 2004
fondaparinux 7.5 mg subcutaneously once daily for at least 5 days and until vitamin K antagonists induced an INR greater than 2.0.
versus
enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an INR greater than 2.0.
patients with acute symptomatic deep venous thrombosisdouble blind
Follow-up duration: 3 months
international
fondaparinux versus heparin
MATISSE PE, 2003
fondaparinux subcutaneously once daily
versus
continuous intravenous infusion of unfractionated heparin
patients with acute symptomatic pulmonary embolismopen
Follow-up duration: 3 mo
heparin+phenprocoumon versus phenylbutazone
Nielsen importé, 1994
heparin and phenprocoumon for 3 months
versus
phenylbutazone
open
Denmark
heparin+warfarin versus placebo
Ott importé, 1998
anticoagulants (s.c. heparin followed by oral warfarin) (duration NA)
versus
s.c. saline followed by oral placebo tablets
double blind
Denmark
heparin/dabigatran versus heparin/VKA
RE-COVER, 2009
NCT00291330
dabigatran 150 mg twice daily in a fixed-dose
versus
warfarin dose-adjusted to an INR between 2.0 and 3.0
patients with acute venous thromboembolism , treated with low molecular weight or unfractionated heparin for 5 to 11 daysdouble blind
Follow-up duration: 6 months
idraparinux versus discontinuation
VanGogh extension, 2007
NCT00071279
once-weekly injections of 2.5 mg of idraparinux for 6 months
versus
placebo
patients who had completed 6 months of prophylaxis with idraparinux or a vitamin K antagonist and in whom extended anticoagulation was warranted
Follow-up duration: 6 months
idraparinux (without heparin) versus heparin/VKA
VanGogh DVT, 2007
NCT00067093
subcutaneous idraparinux (2.5 mg once weekly)
versus
heparin followed by an adjusted-dose vitamin K antagonist
patients with deep-vein thrombosis open
Follow-up duration: 3 mo (6 mo)
VanGogh PE, 2007
NCT00062803
subcutaneous idraparinux (2.5 mg once weekly)
versus
heparin followed by an adjusted-dose vitamin K antagonist
patients with pulmonary embolism open
Follow-up duration: 3 mo (6 mo)
LMWH at home versus UFH in hospital
Koopman, 1996
home treatment with twice daily injections of nadroparin at a dose adjusted for patient’s weight;
versus
UH (APTT adjusted dose, continuous intravenous infusion of 1250 IU per hour after initial intravenous bolus of 5000 IU) in hospital.
patients with acute symptomatic proximal DVT proven by venography or duplex scanopen
Follow-up duration: 12 weeks
The Netherlands, France, Italy, New Zealand Australia
Boccalon, 2000
home treatment with sub-cutaneous injection of LMWH (dalteparin sodium, enoxaparin sodium or nadroparin calciumas chosen by the attending physician) at the recommended dose followed by anticoagulant for 6months
versus
Sub-cutaneous injection of LMWH(dalteparin sodium, enoxaparin sodium or nadroparin calcium as chosen by attending physician) at the recommended dose followed by anticoagulant for 6 months initially in hospital for 10 +/- 2 days then at home
patienst with confirmed diagnosis (by ultrasonography or venography) of proximal DVT not more than 30 days before enrolmentNA
Follow-up duration: 6 months
France
Levine, 1996
home treatment by Sub-cutaneous enoxaparin 1 mg per kg body weight twice a day for at least 5 days
versus
UH (APTT adjusted dose, continuous intravenous infusion of 20,000 IU after initial intravenous bolus of 5000 IU) in hospital for at least 5 days
patients with acute proximal DVT proven on venography or duplex scanopen
Follow-up duration: 90 days
Canada
Ramacciotti, 2004
home treatment by once daily Subcutaneous injection of enoxaparin at a dose of 1.5 mg/kg for 5-10 days
versus
in hospital intravenous bolus injection of 5000 IU of UFH followed by intravenous 500 IU/kg/day adjusted to maintain an aPTT of 1.5-2.5 times the normal value for 5-10 days.
patienst with DVT symptoms for greater than or equal to 10 days and proximal lower limb DVT confirmed by duplex ultrasound or venographyopen
Brazil
Daskalopoulos, 2005
home treatment with single sub- cutaneous injection of LMWH (tinzaparin sodium) in a weight adjusted dose (175 anti Xa IU/Kg) daily for 6 months
versus
Intravenous bolus of 5000IU UFH followed by intrvenous infusion of UFH for 5-7 days. APTT was measured after 4 hours of the initiation of heparin administration and was repeated 6 hours thereafter to reach the therapeutic range (ratio: 1.5-2.5). Oral an
patients with acute proximal DVT confirmed by colour duplex UScan not more than 1 week onsetopen
Greece
Chong, 2005
once daily sub-cutaneous injection of enoxaparin 1.5mg/kg for a minimum of 5 days plus 10mg of warfarin for 3 months adjusted to achieve INR above 2 and within range accepted by the investigator
versus
5000 IU bolus of unfractionated heparin (UFH) for a minimum of 5 days plus 10mg warfarin started on day 1 of the treatment for 3 months
patients with diagnosis of symptomatic lower extrimity DVT (proimal or distal) confirmed by either contrast venography and/or ultrasonography, be suitable for treatment in an outpatient setting open
Follow-up duration: 24 months
Australia, New Zealand, Poland, South Africa
Minoctoparine versus unfractionated heparin
Faivre et al , 1988
Minoctoparine (CY222) Subcutaneous twice daily for 10 Days,155 U/kg BID
versus
unfractionated heparin subcutaneous twice daily APPTx2-3

Follow-up duration: 10 Days
Nadroparin versus acenocoumarol
Lopez-Beret, 2001
LMWH, 1,025 IU/10 kg bid followed by Nadroparin 1,025 IU/10 kg bid
versus
LMWH, 1,025 IU/10 kg bid followed by Acenocoumarol target INR 2-3
patients with objective diagnosis of DVT by compression ultrasonographyopen
Follow-up duration: 6-9 mo
Lopaciuk, 1999
LMWH, 85 UI/kg bid followed by Nadroparin 85 IU/kg qd
versus
LMWH, 85 UI/kg bid followed by Acenocoumarol target INR 2-3
patients with objective diagnosis of DVT by Venographyopen
Follow-up duration: 9 mo
Nadroparin versus unfractionated heparin
Collaborative European Multicentre, 1991
Nadroparin Subcutaneous twice daily for 10 Days, 90 U/kg BID
versus
unfractionated heparin intravenous APPTx1.5-2

Follow-up duration: 12 Weeks
Prandoni et al , 1992
Nadroparin Subcutaneous twice daily for >=0 Days, 90 U/kg BID
versus
unfractionated heparin intravenous APPTx1.5-2

Follow-up duration: 6 Months
Lopaciuk et al , 1992
Nadroparin Subcutaneous twice daily for 10 Days, 92 U/kg BID
versus
unfractionated heparin subcutaneous twice daily APPTx1.5-2.5

Follow-up duration: 3 Months
once daily dalteparin versus twice daily dalteparin
Holmström, 1992
once daily dalteparin 200 U (anti-FXa)/kg for at least 5 days
versus
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 phlebographytioopen
Sweden
Partsch, 1996
Fragmin administered 200 IU/kg once daily for at least 7 days
versus
Fragmin 100 IU/kg twice daily for at least 7 days
patients presented with DVT extending into the iliofemoral segment diagnosed by duplex ultrasonographyANA
Austria
once daily enoxaparin versus twice daily enoxaparin
Merli, 2001
enoxaparin 1.5 mg/kg body weight once daily
versus
S.c. enoxaparin at fixed dosages of 1.0 mg/kg of body weight twice daily
patients with a symptomatic lower-extremity DVT confirmed by venography or ultrasonography (including patients with confirmed PE)double blind
Europe, United States of America and Australia, image/pj
once daily enoxaparin versus UFH
Merli (once daily vs UFH), 2001
Initial therapy with enoxaparin 1.5 mg/kg body weight once daily
versus
Initial therapy with dose-adjusted intravenous unfractionated heparin
patients with a symptomatic lower-extremity DVT confirmed by venography or ultrasonography (including patients with confirmed PE) partialy blinded
Follow-up duration: 3 months
Europe, United States of America and Australia, image/pj
once daily logiparin versus twice daily logiparin
Siegbahn, 1989
Once daily logiparin 150 XaI U/kgp, imag
versus
twice daily logiparin 75 XaI U/kg
patients with a venographically confirmed episode of DVTsingle blind
Sweden and Denmark
once daily nadroparin versus twice daily nadroparin
Charbonnier, 1998
Once daily nadroparin 20,500 (AXa IU/ml)continued for at least 5 days
versus
twice daily nadroparin 10,250 (AXa IU/ml)continued for at least 5 days
patients with acute symptomatic proximal DVT in popliteal vein or above documented by venographydouble blind
Europe
rivaroxaban versus discontinuation
EINSTEIN-extension, 2009
NCT00439725
rivaroxaban 20 mg once-daily for an additional 6 or 12 months
versus
placebo
patients who had completed six to 12 months of anticoagulant treatment for an acute episode of VTEdouble blind
28 countries
rivaroxaban (without LMWH) versus LMWH/VKA
Einstein-DVT Dose-Ranging Study, 2008
rivaroxaban 20, 30, or 40 mg once daily
versus
low-molecular-weight heparin followed by vitamin K antagonists
patients with deep vein thrombosisopen
Einstein-DVT Evaluation, 2010
NCT00440193
rivaroxaban 15 mg twice daily for 3 weeks, then 20 mg daily
versus
enoxaparin 1 mg/kg twice daily >=5 days, then warfarin with target INR between 2-3
Patients with Confirmed Acute Symptomatic Deep-Vein Thrombosis without Pulmonary Embolismopen (assessor-blind)
Einstein-PE Evaluation, 2012
NCT00439777
rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) for 3, 6, or 12 months
versus
standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist
patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosisopen
Follow-up duration: 9.8 months
38 countries
subcutaneous heparin versus intravenous heparin
Krahenbuhl, 1979
subcutaneous sodic heparin 30 000 U daily (mean)
versus
intravenous sodic heparin 30 000 U daily (mean)
Bentley, 1980
subcutaneous calcic heparin 37 000 U daily (mean)
versus
intravenous sodic heparin 36 800 U daily (mean)
Andersson, 1982
subcutaneous sodic heparin 36 800 U daily (mean)
versus
intravenous sodic heparin 33 250 U daily (mean)
Hull, 1986
subcutaneous sodic heparin 32 300 U daily (mean)
versus
intravenous sodic heparin 29 700 U daily (mean)
Doyle, 1987
subcutaneous calcic heparin 29 200 U daily (mean)
versus
intravenous calcic heparin 29 600 U daily (mean)
Walker, 1987
subcutaneous calcic heparin 29 375 U daily (mean)
versus
intravenous calcic heparin 24 384 U daily (mean)
Lopaciuk, 3000
subcutaneous sodic heparin 34 400 U daily (mean)
versus
intravenous sodic heparin 37 000 U daily (mean)
Pini, 1990
subcutaneous calcic heparin 33 800 U daily (mean)
versus
intravenous sodic heparin 31 700 U daily (mean)
Tinzaparin versus acenocoumarol
Romera, 2009
tinzaparin SC 175 IU anti-Xa per kg once daily for 6 months
versus
acenocoumarol for target INR 2-3 for 6 months after initial LMWH (until INR 2-3)
patients with symptomatic proximal DVT of the lowerlimbs confirmed by compression duplex ultrasound scanopen
Follow-up duration: 12 months
Spain
Tinzaparin versus unfractionated heparin
Hull et al , 1992
Tinzaparin Subcutaneous once daily for >= Days, 175 U/kg BID
versus
unfractionated heparin intravenous APPTx2-3

Follow-up duration: 3 Months
Tinzaparin versus warfarin
Hull, 2002
LMWH, 175 IU/kg qd followed by Tinzaparin 175 IU/kg qd
versus
UFH 5 d, followed by UFH therapeutic APTT followed by Warfarin target INR 2-3
patients with objective diagnosis of DVT by Venography/compression ultrasonographyopen
Follow-up duration: 9 mo
warfarin versus discontinuation
PREVENT (Ridker), 2003
extension with low-intensity warfarin (target INR, 1.5 to 2.0)
versus
placebo
Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months
Follow-up duration: 2.1 years
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.
versus
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 embolismopen
Follow-up duration: 33 months
Italy
Agnelli, 2001
continuation for 9 additional months; warfarin or acenocoumarol adjusted to achieve a target INR between 2.0 and 3.0
versus
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 open
Follow-up duration: 33 months
Italy
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.
versus
discontinuation (after 3 months)
patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism
ELAET (Kearon), 2004
continuation for 2 additionnal months of warfarin adjusted to achieve a target INR between 2.0 and 3.0.
versus
discontinuation (after 1 months)
double blind
Follow-up duration: 11 months (after randomizatio)
Canada, US
Levine, 1995
continuation for 2 months of warfarin adjusted INR value of 2.0 to 3.0
versus
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 double blind
Follow-up duration: 11 months after randomization.
Canada, Italy
DURAC (Schulman), 1997
indefinite warfarin or dicoumarol adjusted for a target INR between 2.0 and 2.85
versus
6 months warfarin or dicoumarol adjusted for a target INR between 2.0 and 2.85
open
Follow-up duration: Four years after randomization
Sweden
ximelagatran versus discontinuation
THRIVE III, 2003
ximelagatran 24 mg twice daily for 18 months
versus
placebo for 18 months
patients with venous thromboembolism who had undergone six months of anticoagulant therapydouble blind
Follow-up duration: 18 months
18 countries
ximelagatran versus LMWH/VKA
Fiessinger , 2005
ximelagatran 36 mg twice daily
versus
subcutaneous enoxaparin, 1 mg/kg twice daily, for 5 to 20 days followed by warfarin adjusted to maintain an international normalized ratio of 2.0 to 3.0.
patients with acute deep vein thrombosisdouble blind
ximelagatran (without LMWH) versus LMWH/VKA
THRIVE I, 2003
oral ximelagatran (24, 36, 48 or 60 mg twice daily) for 2 weeks
versus
dalteparin and warfarin for 2 weeks
Patients with acute DVT

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