Fondaparinux antithrombotics

Description Results

Four doses fondaparinux (2.5, 4, 8, or 12 mg once daily) for three to seven days (n=908)

vs.

enoxaparin (1 mg/kg twice daily) for three to seven days (n=230)

Sample size: 908/230

Primary endpoint:

FU duration: 9 days

fondaparinux 2.5 mg daily until hospital discharge or for up to eight days (n=10057)

vs.

enoxaparin 1 mg per kilogram of body weight twice daily for two to eight days or until the patient was in clinically stable condition (n=10021)

double blind

Parallel groups

Sample size: 10057/10021

Primary endpoint: death, myocardial infarction, or refractory ischemia

FU duration: 9 days (180 days)

death in hospital 0.87 [0.76; 0.99]

death or reinfarction 0.87 [0.78; 0.96]

reinfarction during hospitalization 0.68 [0.52; 0.88]

death at 30 dayas 0.87 [0.78; 0.98]

Major bleeding 0.83 [0.64; 1.06]

reinfarction at 30 days 0.81 [0.65; 1.01]

fondaparinux 2.5 mg once daily up to 8 days (n=6036)

vs.

control (UFH or placebo) (n=6056)

from day 3 through day 9, all patients received either fondaparinux or placebo

double-blind

Factorial plan

Sample size: 6036/6056

Primary endpoint: death or reinfarction

FU duration: 30 days

recurrent DVT only 0.71 [0.34; 1.48]

All deaths 1.19 [0.82; 1.73]

Major bleeding 0.85 [0.48; 1.48]

non fatal PE 0.59 [0.31; 1.13]

fatal PE 1.07 [0.53; 2.16]

recurrent VTE 0.75 [0.51; 1.12]

fondaparinux subcutaneously once daily (n=1103)

vs.

continuous intravenous infusion of unfractionated heparin (n=1110)

open

Parallel groups

Sample size: 1103/1110

Primary endpoint: symptomatic recurrent/new VTE

FU duration: 3 mo

symptomatic thromboembolism or death 0.15 [0.08; 0.26]

Deep-venous thrombosis 0.17 [0.05; 0.56]

Venous thromboembolism 0.15 [0.04; 0.50]

PE 0.00 [0.00; NaN]

major bleeding 1.00 [0.06; 15.95]

fondaparinux 2.5mg up to 45 days (n=1502)

vs.

placebo (n=1500)

double blind

Parallel groups

Sample size: 1502/1500

Primary endpoint: symptomatic venous thromboembolism, death

FU duration: 45 days (77d)

DVT 0.46 [0.33; 0.63]

proximal DVT 0.45 [0.21; 0.99]

VTE 0.45 [0.33; 0.62]

Major bleeding 11.00 [1.43; 84.90]

Death 0.67 [0.11; 3.97]

PE 0.25 [0.03; 2.23]

Nonfatal pulmonary embolism 0.25 [0.03; 2.23]

Fatal pulmonary embolism NaN [NaN; NaN]

Symptomatic venous thromboembolism 0.43 [0.11; 1.65]

Symptomatic deep-vein thrombosis 0.75 [0.17; 3.33]

DVT 0.42 [0.31; 0.57]

proximal DVT 0.21 [0.09; 0.51]

VTE 0.44 [0.32; 0.59]

Death 0.70 [0.33; 1.49]

Major bleeding 0.96 [0.51; 1.82]

PE 2.20 [0.45; 10.87]

Nonfatal pulmonary embolism 1.01 [0.06; 16.13]

Fatal pulmonary embolism 1.01 [0.14; 7.16]

Symptomatic venous thromboembolism 1.01 [0.25; 4.03]

Symptomatic deep-vein thrombosis 1.01 [0.06; 16.13]

DVT 0.69 [0.48; 1.00]

Symptomatic venous thromboembolism 10.02 [1.28; 78.13]

Symptomatic deep-vein thrombosis 10.02 [1.28; 78.13]

Death 3.00 [0.31; 28.82]

Major bleeding 1.82 [0.88; 3.78]

PE 5.01 [0.59; 42.81]

proximal DVT 1.42 [0.64; 3.19]

Nonfatal pulmonary embolism ∞ [NaN; ∞]

VTE 0.74 [0.51; 1.05]

Fatal pulmonary embolism 0.00 [0.00; NaN]

DVT 0.44 [0.30; 0.64]

proximal DVT 0.26 [0.11; 0.64]

VTE 0.44 [0.30; 0.64]

Death 0.00 [0.00; NaN]

Major bleeding 1.51 [0.96; 2.35]

PE 0.99 [0.14; 7.05]

Nonfatal pulmonary embolism 0.66 [0.11; 3.96]

Fatal pulmonary embolism NaN [NaN; NaN]

Symptomatic venous thromboembolism 1.66 [0.40; 6.92]

Symptomatic deep-vein thrombosis 2.98 [0.31; 28.65]

All-cause death during follow-up 0.00 [0.00; NaN]

Major bleeding during follow-up 0.97 [0.06; 15.52]

Symptomatic pulmonary embolism during follow-up 0.00 [0.00; NaN]

Symptomatic deep vein thrombosis during follow-up NaN [NaN; NaN]

DVT 0.31 [0.14; 0.73]

VTE 0.31 [0.14; 0.73]

Major bleeding 10.24 [1.31; 79.73]

Death 0.51 [0.05; 5.63]

PE NaN [NaN; NaN]

proximal DVT 0.14 [0.02; 1.14]

Symptomatic venous thromboembolism 1.01 [0.06; 16.18]

Death 0.75 [0.38; 1.45]

Major bleeding 1.39 [0.91; 2.13]

PE 1.66 [0.40; 6.95]

DVT 0.72 [0.49; 1.06]

proximal DVT 1.00 [0.29; 3.45]

Nonfatal pulmonary embolism ∞ [NaN; ∞]

VTE 0.75 [0.52; 1.09]

Fatal pulmonary embolism 1.00 [0.20; 4.94]

Symptomatic venous thromboembolism 1.20 [0.37; 3.92]

Symptomatic deep-vein thrombosis 1.00 [0.14; 7.08]

Major bleeding 0.92 [0.41; 2.07]

DVT 0.25 [0.03; 2.22]

Major bleeding NaN [NaN; NaN]

VTE 0.78 [0.05; 11.67]

fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery (n=517)

vs.

enoxaparin 30mg twice daily (North america recommendation) (n=517)

double blind

Parallel groups

Sample size: 517/517

Primary endpoint: venous thromboembolism

FU duration: 11 days

fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery (n=831)

vs.

enoxaprin 40mg once daily (n=840)

double blind

Parallel groups

Sample size: 831/840

Primary endpoint: venous thromboembolism

FU duration: 11 days

fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery (n=1138)

vs.

enoxaparin 30mg twice daily (North america recommendation) (n=1137)

double blind

Parallel groups

Sample size: 1138/1137

Primary endpoint: venous thromboembolism

FU duration: 11 days

fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery (n=1155)

vs.

enoxaprin 40mg once daily (n=1154)

double blind

Parallel groups

Sample size: 1155/1154

Primary endpoint: venous thromboembolism

FU duration: 11 days (6 weeks)

pentasaccharide Org31540/SR90107A subcutaneous once daily at doses 0.75 mg, 1.5 mg, 3.0 mg, 6.0 mg, and 8.0 mg (n=673)

vs.

enoxaparin 30mg once daily subcutaneous (n=260)

dose-ranging study

double blind

Parallel groups

Sample size: 673/260

Primary endpoint: venous thromboembolism

FU duration: >15 days

dose finding study

Fondaparinux 2.5 mg once daily for 6–14 days (n=425)

vs.

placebo (n=414)

double blind

Parallel groups

Sample size: 425/414

Primary endpoint: venous thromboembolism

FU duration: 6-15 days

fondaparinux 2.5 mg s.c. for 5-9 days, starting 6-8 h postoperatively + intermittent pneumatic compression (n=650)

vs.

placebo s.c. for 5-9 days, starting 6-8 h postoperatively + intermittent pneumatic compression (n=659)

double blind

Parallel groups

Sample size: 650/659

Primary endpoint: venous thromboembolism up to day 10

FU duration: 10 days

once-daily subcutaneous injections of fondaparinux 2·5 mg started 6 h after surgery for 5–9 days (n=1465)

vs.

once-daily subcutaneous injections of dalteparin 5000 units for 5–9 days (2500 units each, given 2 h before surgery and 12 h after the preoperative administration) (n=1462)

double blind

Parallel groups

Sample size: 1465/1462

Primary endpoint: venous thromboembolism

FU duration: 10 days (30 days)

fondaparinux 2.5mg qd (n=-9)

vs.

enoxaparin 40mg qd (n=-9)

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration:

fondaparinux 2.5mg subcutaneous once-daily for 7+/-2 days (n=119)

vs.

enoxaparin 40mg s.c. once-daily (n=118)

single-blind

Parallel groups

Sample size: 119/118

Primary endpoint: overall deep vein thrombosis

FU duration: 9 days (49d)

Fondaparinux 2.5mg once daily subcutaneously for 7 days (n=28)

vs.

enoxaparin 40mg once daily SC for 7 days (n=23)

open, blind assessment

Parallel groups

Sample size: 28/23

Primary endpoint: VTE events

FU duration: 10 days

fondaparinux subcutaneously at 0.75, 1.5, 2.5, and 3.0 mg for at least 10 calendar days, (with a maximum of 14 days) (n=345)

vs.

placebo (n=87)

double blind

Parallel groups

Sample size: 345/87

Primary endpoint: VTE

FU duration: 14 days

dose response study

Recurrent DVT/DVT extension (symptomatic) 0.96 [0.64; 1.45]

All-cause mortality 1.25 [0.80; 1.97]

Major hemorrhage 1.09 [0.64; 1.84]

Non-fatal PE 1.68 [0.83; 3.42]

Fatal PE 1.01 [0.29; 3.47]

recurrent DVT only 0.71 [0.34; 1.48]

All deaths 1.19 [0.82; 1.73]

Major bleeding 0.85 [0.48; 1.48]

non fatal PE 0.59 [0.31; 1.13]

fatal PE 1.07 [0.53; 2.16]

recurrent VTE 0.75 [0.51; 1.12]

fondaparinux 7.5 mg subcutaneously once daily for at least 5 days and until vitamin K antagonists induced an INR greater than 2.0. (n=1098)

vs.

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. (n=1107)

double blind

Parallel groups

Sample size: 1098/1107

Primary endpoint: symptomatic recurrent venous thromboembolic

FU duration: 3 months

fondaparinux subcutaneously once daily (n=1103)

vs.

continuous intravenous infusion of unfractionated heparin (n=1110)

open

Parallel groups

Sample size: 1103/1110

Primary endpoint: symptomatic recurrent/new VTE

FU duration: 3 mo