| pathology | Demonstrated benefit and harm | k | | | |
|---|
| acute coronary syndrome | versus LMWH No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PENTUA, 2004 | fondaparinux vs enoxaparin | | | | | OASIS 5, 2006 | fondaparinux vs enoxaparin | | | |
| Trial | Treatments | Patients | Method |
|---|
| PENTUA, 2004 | 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) | patients with ACS without persistent
ST-segment elevation | Sample size: 908/230 Primary endpoint: FU duration: 9 days | | OASIS 5, 2006 | 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) | patients with acute coronary syndromes | double blind Parallel groups Sample size: 10057/10021 Primary endpoint: death, myocardial infarction, or refractory ischemia FU duration: 9 days (180 days) |
|
| acute myocardial infarction | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| MICHELANGELO OASIS-6, 2006 | fondaparinux vs placebo | 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] |
| Trial | Treatments | Patients | Method |
|---|
| MICHELANGELO OASIS-6, 2006 | 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 | patients with STEMI | double-blind Factorial plan Sample size: 6036/6056 Primary endpoint: death or reinfarction FU duration: 30 days |
|
| pulmonary embolism | versus heparin/VKA No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| MATISSE PE, 2003 | fondaparinux vs heparin | | | 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] |
| Trial | Treatments | Patients | Method |
|---|
| MATISSE PE, 2003 | fondaparinux subcutaneously once daily (n=1103) vs. continuous intravenous infusion of unfractionated
heparin (n=1110) | patients with acute symptomatic pulmonary embolism | open Parallel groups Sample size: 1103/1110 Primary endpoint: symptomatic recurrent/new VTE FU duration: 3 mo |
|
| superficial thrombophlebitis | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CALISTO, 2010 | fondaparinux vs placebo | 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] |
| Trial | Treatments | Patients | Method |
|---|
| CALISTO, 2010 | fondaparinux 2.5mg up to 45 days (n=1502) vs. placebo (n=1500) | patients with acute symptomatic isolated superficial thrombophlebitis of the lower limbs | double blind Parallel groups Sample size: 1502/1500 Primary endpoint: symptomatic venous thromboembolism, death FU duration: 45 days (77d) |
|
| thrombosis prevention | versus placebo or control No demonstrated result for efficacy fondaparinux inferior to placebo (on top intermittent pneumatic comp.) in terms of Major bleeding in APOLLO (Turpie), 2007 (abdominal surgery patients) | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ARTEMIS (Cohen), 2006 | fondaparinux vs placebo | | | 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] | | APOLLO (Turpie), 2007 | fondaparinux vs placebo (on top intermittent pneumatic comp.) | 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] | | DRI4757 | fondaparinux vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| ARTEMIS (Cohen), 2006 | Fondaparinux 2.5 mg once daily for 6–14 days (n=425) vs. placebo
(n=414)
| High-risk medical patients
| double blind Parallel groups Sample size: 425/414 Primary endpoint: venous thromboembolism FU duration: 6-15 days
| | APOLLO (Turpie), 2007 | 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) | Patients aged at least 40 years undergoing abdominal surgery | double blind Parallel groups Sample size: 650/659 Primary endpoint: venous thromboembolism up to day 10 FU duration: 10 days | | DRI4757 | 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) | Japanese patients undergoing elective total knee replacement surgery | double blind Parallel groups Sample size: 345/87 Primary endpoint: VTE FU duration: 14 days dose response study |
|
| thrombosis prevention | versus LMWH No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| BRiEF | fondaparinux vs enoxaparin | | | |
| Trial | Treatments | Patients | Method |
|---|
| BRiEF | fondaparinux 2.5mg qd (n=-9) vs. enoxaparin 40mg qd (n=-9) | acute medically ill, non-surgical patients | Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: |
|
| thrombosis prevention | versus Low molecular weight heparin No demonstrated result for efficacy fondaparinux inferior to enoxaparin in terms of Major bleeding in PENTAMAKS (Bauer), 2001 (knee surgery patients) fondaparinux inferior to enoxaparin in terms of Symptomatic venous thromboembolism in PENTATHLON (Turpie), 2002 (hip surgery patients) fondaparinux inferior to enoxaparin in terms of Symptomatic deep-vein thrombosis in PENTATHLON (Turpie), 2002 (hip surgery patients) | 8 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PENTAMAKS (Bauer), 2001 | fondaparinux vs enoxaparin | 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] | | PENTHIFRA (Eriksson), 2001 | fondaparinux vs enoxaparin | 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] | | PENTATHLON (Turpie), 2002 | fondaparinux vs enoxaparin | 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] | | EPHESUS (Lassen), 2002 | fondaparinux vs enoxaparin | 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] | | Turpie, 2001 | fondaparinux vs enoxaparin | | | | | PEGASUS, 2005 | fondaparinux vs enoxaparin | | | 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] | | L8541 | fondaparinux vs enoxaparin | | | Major bleeding 0.92 [0.41; 2.07] DVT 0.25 [0.03; 2.22] | | L8635 | fondaparinux vs enoxaparin | | | Major bleeding NaN [NaN; NaN] VTE 0.78 [0.05; 11.67] |
| Trial | Treatments | Patients | Method |
|---|
| PENTAMAKS (Bauer), 2001 | fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery (n=517) vs. enoxaparin 30mg twice daily (North america recommendation) (n=517) | elective major knee surgery | double blind Parallel groups Sample size: 517/517 Primary endpoint: venous thromboembolism FU duration: 11 days | | PENTHIFRA (Eriksson), 2001 | fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery (n=831) vs. enoxaprin 40mg once daily (n=840) | hip fracture surgery | double blind Parallel groups Sample size: 831/840 Primary endpoint: venous thromboembolism FU duration: 11 days | | PENTATHLON (Turpie), 2002 | fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery (n=1138) vs. enoxaparin 30mg twice daily (North america recommendation) (n=1137) | elective hip replacement surgery | double blind Parallel groups Sample size: 1138/1137 Primary endpoint: venous thromboembolism FU duration: 11 days | | EPHESUS (Lassen), 2002 | fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery (n=1155) vs. enoxaprin 40mg once daily (n=1154) | elective hip replacement surgery | double blind Parallel groups Sample size: 1155/1154 Primary endpoint: venous thromboembolism FU duration: 11 days (6 weeks) | | Turpie, 2001 | 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 | patients undergoing total hip replacement | double blind Parallel groups Sample size: 673/260 Primary endpoint: venous thromboembolism FU duration: >15 days dose finding study | | PEGASUS, 2005 | 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) | patients undergoing major abdominal surgery | double blind Parallel groups Sample size: 1465/1462 Primary endpoint: venous thromboembolism FU duration: 10 days (30 days) | | L8541 | fondaparinux 2.5mg subcutaneous once-daily for 7+/-2 days (n=119) vs. enoxaparin 40mg s.c. once-daily (n=118) | chinese patients undergoing major orthopaedic surgery of the lower limbs | single-blind Parallel groups Sample size: 119/118 Primary endpoint: overall deep vein thrombosis FU duration: 9 days (49d) | | L8635 | Fondaparinux 2.5mg once daily subcutaneously for 7 days (n=28) vs. enoxaparin 40mg once daily SC for 7 days (n=23) | Taiwanese patients undergoing elective knee replacement | open, blind assessment Parallel groups Sample size: 28/23 Primary endpoint: VTE events FU duration: 10 days |
|
| venous thrombosis | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| MATISSE, 2004 | fondaparinux vs enoxaparin | | | 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] |
| Trial | Treatments | Patients | Method |
|---|
| 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. (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) | patients with acute symptomatic deep venous thrombosis | double blind Parallel groups Sample size: 1098/1107 Primary endpoint: symptomatic recurrent venous thromboembolic FU duration: 3 months |
|
| venous thrombosis | versus heparin/VKA No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| MATISSE PE, 2003 | fondaparinux vs heparin | | | 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] |
| Trial | Treatments | Patients | Method |
|---|
| MATISSE PE, 2003 | fondaparinux subcutaneously once daily (n=1103) vs. continuous intravenous infusion of unfractionated
heparin (n=1110) | patients with acute symptomatic pulmonary embolism | open Parallel groups Sample size: 1103/1110 Primary endpoint: symptomatic recurrent/new VTE FU duration: 3 mo |
|
