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Meta-Analysis
. 2016 Oct 31;10(10):CD005134.
doi: 10.1002/14651858.CD005134.pub3.

Pentasaccharides for the prevention of venous thromboembolism

Kezhou Dong  1 , Yanzhi Song, Xiaodong Li, Jie Ding, Zhiyong Gao, Daopei Lu, Yimin Zhu
Affiliations
Meta-Analysis

Pentasaccharides for the prevention of venous thromboembolism

Kezhou Dong et al. Cochrane Database Syst Rev. .

Abstract

Background: Venous thromboembolism (VTE) is a common condition with potentially serious and life-threatening consequences. The standard method of thromboprophylaxis uses an anticoagulant such as low molecular weight heparin (LMWH) or warfarin. In recent years, another type of anticoagulant, pentasaccharide, an indirect factor Xa inhibitor, has shown good anticoagulative effect in clinical trials. Three types of pentasaccharides are available: short-acting fondaparinux, long-acting idraparinux and idrabiotaparinux. Pentasaccharides cause little heparin-induced thrombocytopenia and are better tolerated than unfractionated heparin, LMWH and warfarin. However, no consensus has been reached on whether pentasaccharides are superior or inferior to other anticoagulative methods.

Objectives: To assess effects of pentasaccharides versus other methods of thromboembolic prevention (thromboprophylaxis) in people who require anticoagulant treatment to prevent venous thromboembolism.

Search methods: The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched March 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2). The CIS searched trial databases for details of ongoing and unpublished studies. Review authors searched LILACS (Latin American and Caribbean Health Sciences) and the reference lists of relevant studies and reviews identified by electronic searches.

Selection criteria: We included randomised controlled trials on any type of pentasaccharide versus other anticoagulation methods (pharmaceutical or mechanical) for VTE prevention.

Data collection and analysis: Two review authors independently selected trials, assessed methodological quality and extracted data in predesigned tables.

Main results: We included in this review 25 studies with a total of 21,004 participants. All investigated fondaparinux for VTE prevention; none investigated idraparinux or idrabiotaparinux. Studies included participants undergoing abdominal surgery, thoracic surgery, bariatric surgery or coronary bypass surgery; acutely ill hospitalised medical patients; people requiring rigid or semirigid immobilisation; and those with superficial venous thrombosis. Most studies focused on orthopaedic patients. We lowered the quality of the evidence because of heterogeneity between studies and a small number of events causing imprecision.When comparing fondaparinux with placebo, we found less total VTE (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.15 to 0.38; 5717 participants; 8 studies; I2 = 64%; P < 0.00001), less symptomatic VTE (RR 0.15, 95% CI 0.06 to 0.36; 6503 participants; 8 studies; I2 = 0%; P < 0.0001), less total DVT (RR 0.25, 95% CI 0.15 to 0.40; 5715 participants; 8 studies; I2 = 67%; P < 0.00001), less proximal DVT (RR 0.12, 95% CI 0.04 to 0.39; 2746 participants; 7 studies; I2 = 64%; P = 0.0004) and less total pulmonary embolism (PE) (RR 0.16, 95% CI 0.04 to 0.62; 6412 participants; 8 studies; I2 = 0%; P = 0.008) in the fondaparinux group. The quality of the evidence was moderate for total VTE, total DVT and proximal DVT, and high for symptomatic VTE and total PE.When fondaparinux was compared with LMWH, analyses indicated that fondaparinux reduced total VTE and DVT (RR 0.55, 95% CI 0.42 to 0.73; 9339 participants; 11 studies; I2 = 64%; P < 0.0001; and RR 0.54, 95% CI 0.40 to 0.71; 9356 participants; 10 studies; I2 = 67%; P < 0.0001, respectively), and showed a trend toward reduced proximal DVT (RR 0.58, 95% CI 0.33 to 1.02; 8361 participants; 9 studies; I2 = 53%; P = 0.06). Symptomatic VTE (RR 1.03, 95% CI 0.65 to 1.63; 12240 participants; 9 studies; I2 = 35%; P = 0.90) and total PE (RR 1.24, 95% CI 0.65 to 2.34; 12350 participants; 10 studies; I2 = 0%; P = 0.51) indicated no difference between fondaparinux and LMWH. The quality of the evidence was moderate for total VTE, symptomatic VTE, total DVT and total PE, and low for proximal DVT.We showed that fondaparinux increased major bleeding compared with both placebo and LWMH (RR 2.56, 95% CI 1.48 to 4.44; 6659 participants; 8 studies; I2 = 0%; P = 0.0008; moderate-quality evidence; and RR 1.38, 95% CI 1.09 to 1.75; 12,501 participants; 11 studies; I2 = 24%; P = 0.008; high-quality evidence, respectively). All-cause mortality was not different between fondaparinux and placebo or LMWH (RR 0.76, 95% CI 0.48 to 1.22; 6674 participants; 8 studies; I2 = 14%; P = 0.26; moderate-quality evidence; and RR 0.88, 95% CI 0.63 to 1.22; 12,400 participants; 11 studies; I2 = 0%; P = 0.44; moderate-quality evidence, respectively).One study compared fondaparinux with variable and fixed (1 mg per day) doses of warfarin after elective hip or knee replacement surgery and showed no difference in primary and secondary outcomes between fondaparinux and both variable and fixed doses of warfarin. The quality of the evidence was very low. One small study compared fondaparinux with edoxaban in patients with severe renal impairment undergoing lower-limb orthopaedic surgery and reported no thromboembolic events, major bleeding events or deaths in either group. The quality of the evidence was very low. One small study compared fondaparinux with mechanical thromboprophylaxis. Results showed no difference in total VTE and total DVT between fondaparinux and mechanical thromboprophylaxis. This study reported no cases pertaining to the other outcomes of this review. The quality of the evidence was low.There were insufficient studies to permit meaningful conclusions for subgroups of clinical conditions other than orthopaedic surgery.

Authors' conclusions: Moderate to high quality evidence shows that fondaparinux is effective for short-term prevention of VTE when compared with placebo. It can reduce total VTE, DVT, total PE and symptomatic VTE, and does not demonstrate a reduction in deaths compared with placebo. Low to moderate quality evidence shows that fondaparinux is more effective for short-term VTE prevention when compared with LMWH. It can reduce total VTE and total DVT and does not demonstrate a reduction in deaths when compared with LMWH. However, at the same time, moderate to high quality evidence shows that fondaparinux increases major bleeding when compared with placebo and LMWH. Therefore, when fondaparinux is chosen for the prevention of VTE, attention should be paid to the person's bleeding and thrombosis risks. Most data were derived from patients undergoing orthopaedic surgery. Therefore, the conclusion predominantly pertains to these patients. Data on fondaparinux for other clinical conditions are sparse.

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Conflict of interest statement

KD: none known. YS: none known. XL: none known. JD: none known. ZG: none known. DL:none known. YZ: none known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot of comparison: 1 fondaparinux versus placebo, outcome: 1.1 total VTE.
5
5
Funnel plot of comparison: 5 fondaparinux versus LMWH, outcome: 5.1 total VTE.
1.1
1.1. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 1 total VTE.
1.2
1.2. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 2 symptomatic VTE.
1.3
1.3. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 3 total DVT.
1.4
1.4. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 4 proximal DVT.
1.5
1.5. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 5 total PE.
1.6
1.6. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 6 fatal PE.
1.7
1.7. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 7 non‐fatal PE.
1.8
1.8. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 8 major bleeding.
1.9
1.9. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 9 fatal bleeding.
1.10
1.10. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 10 MI.
1.11
1.11. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 11 all causes of death.
1.12
1.12. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 12 other serious adverse effects.
2.1
2.1. Analysis
Comparison 2 Fondaparinux versus placebo sensitivity analysis inserting Yokote 2011, Outcome 1 total VTE.
2.2
2.2. Analysis
Comparison 2 Fondaparinux versus placebo sensitivity analysis inserting Yokote 2011, Outcome 2 symptomatic VTE.
2.3
2.3. Analysis
Comparison 2 Fondaparinux versus placebo sensitivity analysis inserting Yokote 2011, Outcome 3 total DVT.
2.4
2.4. Analysis
Comparison 2 Fondaparinux versus placebo sensitivity analysis inserting Yokote 2011, Outcome 4 proximal DVT.
2.5
2.5. Analysis
Comparison 2 Fondaparinux versus placebo sensitivity analysis inserting Yokote 2011, Outcome 5 total PE.
2.6
2.6. Analysis
Comparison 2 Fondaparinux versus placebo sensitivity analysis inserting Yokote 2011, Outcome 6 fatal PE.
2.7
2.7. Analysis
Comparison 2 Fondaparinux versus placebo sensitivity analysis inserting Yokote 2011, Outcome 7 non‐fatal PE.
2.8
2.8. Analysis
Comparison 2 Fondaparinux versus placebo sensitivity analysis inserting Yokote 2011, Outcome 8 major bleeding.
2.9
2.9. Analysis
Comparison 2 Fondaparinux versus placebo sensitivity analysis inserting Yokote 2011, Outcome 9 fatal bleeding.
2.10
2.10. Analysis
Comparison 2 Fondaparinux versus placebo sensitivity analysis inserting Yokote 2011, Outcome 10 all causes of death.
3.1
3.1. Analysis
Comparison 3 Fondaparinux versus placebo sensitivity analysis excluding CALISTO, Outcome 1 total VTE.
3.2
3.2. Analysis
Comparison 3 Fondaparinux versus placebo sensitivity analysis excluding CALISTO, Outcome 2 symptomatic VTE.
3.3
3.3. Analysis
Comparison 3 Fondaparinux versus placebo sensitivity analysis excluding CALISTO, Outcome 3 total DVT.
3.4
3.4. Analysis
Comparison 3 Fondaparinux versus placebo sensitivity analysis excluding CALISTO, Outcome 4 proximal DVT.
3.5
3.5. Analysis
Comparison 3 Fondaparinux versus placebo sensitivity analysis excluding CALISTO, Outcome 5 total PE.
3.6
3.6. Analysis
Comparison 3 Fondaparinux versus placebo sensitivity analysis excluding CALISTO, Outcome 6 fatal PE.
3.7
3.7. Analysis
Comparison 3 Fondaparinux versus placebo sensitivity analysis excluding CALISTO, Outcome 7 non‐fatal PE.
3.8
3.8. Analysis
Comparison 3 Fondaparinux versus placebo sensitivity analysis excluding CALISTO, Outcome 8 major bleeding.
3.9
3.9. Analysis
Comparison 3 Fondaparinux versus placebo sensitivity analysis excluding CALISTO, Outcome 9 fatal bleeding.
3.10
3.10. Analysis
Comparison 3 Fondaparinux versus placebo sensitivity analysis excluding CALISTO, Outcome 10 MI.
3.11
3.11. Analysis
Comparison 3 Fondaparinux versus placebo sensitivity analysis excluding CALISTO, Outcome 11 all causes of death.
3.12
3.12. Analysis
Comparison 3 Fondaparinux versus placebo sensitivity analysis excluding CALISTO, Outcome 12 other serious adverse effects.
4.1
4.1. Analysis
Comparison 4 Fondaparinux versus placebo subgroup analysis, Outcome 1 total VTE.
4.2
4.2. Analysis
Comparison 4 Fondaparinux versus placebo subgroup analysis, Outcome 2 symptomatic VTE.
4.3
4.3. Analysis
Comparison 4 Fondaparinux versus placebo subgroup analysis, Outcome 3 total DVT.
4.4
4.4. Analysis
Comparison 4 Fondaparinux versus placebo subgroup analysis, Outcome 4 proximal DVT.
4.5
4.5. Analysis
Comparison 4 Fondaparinux versus placebo subgroup analysis, Outcome 5 total PE.
4.6
4.6. Analysis
Comparison 4 Fondaparinux versus placebo subgroup analysis, Outcome 6 fatal PE.
4.7
4.7. Analysis
Comparison 4 Fondaparinux versus placebo subgroup analysis, Outcome 7 non‐fatal PE.
4.8
4.8. Analysis
Comparison 4 Fondaparinux versus placebo subgroup analysis, Outcome 8 major bleeding.
4.9
4.9. Analysis
Comparison 4 Fondaparinux versus placebo subgroup analysis, Outcome 9 fatal bleeding.
4.10
4.10. Analysis
Comparison 4 Fondaparinux versus placebo subgroup analysis, Outcome 10 MI.
4.11
4.11. Analysis
Comparison 4 Fondaparinux versus placebo subgroup analysis, Outcome 11 all causes of death.
4.12
4.12. Analysis
Comparison 4 Fondaparinux versus placebo subgroup analysis, Outcome 12 other serious adverse effects.
5.1
5.1. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 1 total VTE.
5.2
5.2. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 2 symptomatic VTE.
5.3
5.3. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 3 total DVT.
5.4
5.4. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 4 proximal DVT.
5.5
5.5. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 5 total PE.
5.6
5.6. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 6 fatal PE.
5.7
5.7. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 7 non‐fatal PE.
5.8
5.8. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 8 major bleeding.
5.9
5.9. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 9 fatal bleeding.
5.10
5.10. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 10 MI.
5.11
5.11. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 11 all causes of death.
5.12
5.12. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 12 death associated with VTE or bleeding.
5.13
5.13. Analysis
Comparison 5 Fondaparinux versus LMWH, Outcome 13 other serious adverse effects.
6.1
6.1. Analysis
Comparison 6 Fondaparinux versus LMWH sensitivity analysis, Outcome 1 total VTE.
6.2
6.2. Analysis
Comparison 6 Fondaparinux versus LMWH sensitivity analysis, Outcome 2 symptomatic VTE.
6.3
6.3. Analysis
Comparison 6 Fondaparinux versus LMWH sensitivity analysis, Outcome 3 total DVT.
6.4
6.4. Analysis
Comparison 6 Fondaparinux versus LMWH sensitivity analysis, Outcome 4 proximal DVT.
6.5
6.5. Analysis
Comparison 6 Fondaparinux versus LMWH sensitivity analysis, Outcome 5 total PE.
6.6
6.6. Analysis
Comparison 6 Fondaparinux versus LMWH sensitivity analysis, Outcome 6 fatal PE.
6.7
6.7. Analysis
Comparison 6 Fondaparinux versus LMWH sensitivity analysis, Outcome 7 non‐fatal PE.
6.8
6.8. Analysis
Comparison 6 Fondaparinux versus LMWH sensitivity analysis, Outcome 8 major bleeding.
6.9
6.9. Analysis
Comparison 6 Fondaparinux versus LMWH sensitivity analysis, Outcome 9 fatal bleeding.
6.10
6.10. Analysis
Comparison 6 Fondaparinux versus LMWH sensitivity analysis, Outcome 10 all causes of death.
6.11
6.11. Analysis
Comparison 6 Fondaparinux versus LMWH sensitivity analysis, Outcome 11 other serious adverse effects.
7.1
7.1. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 1 total VTE.
7.2
7.2. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 2 symptomatic VTE.
7.3
7.3. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 3 total DVT.
7.4
7.4. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 4 proximal DVT.
7.5
7.5. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 5 total PE.
7.6
7.6. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 6 fatal PE.
7.7
7.7. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 7 non‐fatal PE.
7.8
7.8. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 8 major bleeding.
7.9
7.9. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 9 fatal bleeding.
7.10
7.10. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 10 MI.
7.11
7.11. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 11 all causes of death.
7.12
7.12. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 12 death associated with VTE or bleeding.
7.13
7.13. Analysis
Comparison 7 Fondaparinux versus LMWH sensitivity analysis without EFFORT, Outcome 13 other serious adverse effects.
8.1
8.1. Analysis
Comparison 8 Fondaparinux versus LMWH subgroup analysis, Outcome 1 total VTE.
8.2
8.2. Analysis
Comparison 8 Fondaparinux versus LMWH subgroup analysis, Outcome 2 symptomatic VTE.
8.3
8.3. Analysis
Comparison 8 Fondaparinux versus LMWH subgroup analysis, Outcome 3 total DVT.
8.4
8.4. Analysis
Comparison 8 Fondaparinux versus LMWH subgroup analysis, Outcome 4 proximal DVT.
8.5
8.5. Analysis
Comparison 8 Fondaparinux versus LMWH subgroup analysis, Outcome 5 total PE.
8.6
8.6. Analysis
Comparison 8 Fondaparinux versus LMWH subgroup analysis, Outcome 6 fatal PE.
8.7
8.7. Analysis
Comparison 8 Fondaparinux versus LMWH subgroup analysis, Outcome 7 non‐fatal PE.
8.8
8.8. Analysis
Comparison 8 Fondaparinux versus LMWH subgroup analysis, Outcome 8 major bleeding.
8.9
8.9. Analysis
Comparison 8 Fondaparinux versus LMWH subgroup analysis, Outcome 9 fatal bleeding.
8.10
8.10. Analysis
Comparison 8 Fondaparinux versus LMWH subgroup analysis, Outcome 10 MI.
8.11
8.11. Analysis
Comparison 8 Fondaparinux versus LMWH subgroup analysis, Outcome 11 all causes of death.
8.12
8.12. Analysis
Comparison 8 Fondaparinux versus LMWH subgroup analysis, Outcome 12 other serious adverse effects.
9.1
9.1. Analysis
Comparison 9 Fondaparinux versus variable dose warfarin, Outcome 1 total VTE.
9.2
9.2. Analysis
Comparison 9 Fondaparinux versus variable dose warfarin, Outcome 2 symptomatic VTE.
9.3
9.3. Analysis
Comparison 9 Fondaparinux versus variable dose warfarin, Outcome 3 total DVT.
9.4
9.4. Analysis
Comparison 9 Fondaparinux versus variable dose warfarin, Outcome 4 proximal DVT.
9.5
9.5. Analysis
Comparison 9 Fondaparinux versus variable dose warfarin, Outcome 5 total PE.
9.6
9.6. Analysis
Comparison 9 Fondaparinux versus variable dose warfarin, Outcome 6 major bleeding.
9.7
9.7. Analysis
Comparison 9 Fondaparinux versus variable dose warfarin, Outcome 7 all causes of death.
10.1
10.1. Analysis
Comparison 10 Fondaparinux versus 1 mg warfarin, Outcome 1 total VTE.
10.2
10.2. Analysis
Comparison 10 Fondaparinux versus 1 mg warfarin, Outcome 2 symptomatic VTE.
10.3
10.3. Analysis
Comparison 10 Fondaparinux versus 1 mg warfarin, Outcome 3 total DVT.
10.4
10.4. Analysis
Comparison 10 Fondaparinux versus 1 mg warfarin, Outcome 4 proximal DVT.
10.5
10.5. Analysis
Comparison 10 Fondaparinux versus 1 mg warfarin, Outcome 5 total PE.
10.6
10.6. Analysis
Comparison 10 Fondaparinux versus 1 mg warfarin, Outcome 6 major bleeding.
10.7
10.7. Analysis
Comparison 10 Fondaparinux versus 1 mg warfarin, Outcome 7 all causes of death.
11.1
11.1. Analysis
Comparison 11 Fondaparinux versus edoxaban, Outcome 1 total VTE.
11.2
11.2. Analysis
Comparison 11 Fondaparinux versus edoxaban, Outcome 2 major bleeding.
11.3
11.3. Analysis
Comparison 11 Fondaparinux versus edoxaban, Outcome 3 all causes of death.
12.1
12.1. Analysis
Comparison 12 Fondaparinux versus mechanical thromboprophylaxis, Outcome 1 total VTE.
12.2
12.2. Analysis
Comparison 12 Fondaparinux versus mechanical thromboprophylaxis, Outcome 2 symptomatic VTE.
12.3
12.3. Analysis
Comparison 12 Fondaparinux versus mechanical thromboprophylaxis, Outcome 3 total DVT.
12.4
12.4. Analysis
Comparison 12 Fondaparinux versus mechanical thromboprophylaxis, Outcome 4 proximal DVT.
12.5
12.5. Analysis
Comparison 12 Fondaparinux versus mechanical thromboprophylaxis, Outcome 5 total PE.
12.6
12.6. Analysis
Comparison 12 Fondaparinux versus mechanical thromboprophylaxis, Outcome 6 major bleeding.
12.7
12.7. Analysis
Comparison 12 Fondaparinux versus mechanical thromboprophylaxis, Outcome 7 all causes of death.
12.8
12.8. Analysis
Comparison 12 Fondaparinux versus mechanical thromboprophylaxis, Outcome 8 other serious adverse effects.
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Update of

  • doi: 10.1002/14651858.CD005134.pub2

References

References to studies included in this review

ACT2545 {published data only}
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APOLLO {published data only}
    1. Anon. Safety study of fondaparinux sodium to prevent venous thromboembolic events (APOLLO). A multicenter, randomized, double‐blind, parallel group trial to demonstrate the efficacy of fondaparinux sodium in association with intermittent pneumatic compression versus intermittent pneumatic compression used alone for the prevention of venous thromboembolic events in subjects at increased risk undergoing major abdominal surgery. GlaxoSmithKline Clinical Trial Register 2011; Vol. Study No: AR3103414. [URL: www.gsk‐clinicalstudyregister.com/study/103414 (accessed 22 July 2014)]
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AR3106116 {published data only}
    1. Anon. Clinical evaluation of GSK576428 (fondaparinux sodium) in prevention of venous thromboembolism (VTE) after abdominal surgery. GlaxoSmithKline Clinical Trial Register 2008. [URL: www.gsk‐clinicalstudyregister.com/study/AR3106116 (accessed 22 July 2014)]
    1. Sakon M, Tsukamoto T, Kobayashi T, Fujita S, Kawashima T, Morito M. Clinical evaluation of fondaparinux for prevention of venous thromboembolism after abdominal surgery. A randomized open‐label study of fondaparinux and intermittent pneumatic compression as a benchmark. Rinsho Iyaku ‐ Journal of Clinical Therapeutics & Medicines 2008;24(7):679‐89.
ARTEMIS {published data only}
    1. Anon. A multinational, randomized, double‐blind comparison of once daily subcutaneous fondaparinux sodium with placebo for the prevention of venous thromboembolic events in acutely ill medical patients (ARTEMIS). GlaxoSmithKline Clinical Trial Register 2008. [URL: www.gsk‐clinicalstudyregister.com/study/104619 (accessed 22 July 2014)]
    1. Cohen AT. Thromboprophylaxis with fondaparinux in acutely ill medical patients aged 75 years or more. The Hematology Journal 2004;5(Suppl 2):105.
    1. Cohen AT. Thromboprophylaxis with fondaparinux in acutely ill medical patients with moderate renal impairment. The Hematology Journal 2004;5(Suppl 2):54.
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    1. Cohen AT, Davidson BL, Gallus AS, Lassen MR, Prins MH, Tomkowski W, et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 2006;332(7537):325‐9. - PMC - PubMed
Bern 2015 {published data only}
    1. Bern MM, Hazel D, Deeran E, Richmond JR, Ward DM, Spitz DJ, et al. Low dose compared to variable dose warfarin and to fondaparinux as prophylaxis for thromboembolism after elective hip or knee replacement surgery; a randomized, prospective study. Thrombosis Journal 2015;13(32):672‐83. [DOI: 10.1186/s12959-015-0062-0] - DOI - PMC - PubMed
CALISTO {published data only}
    1. Anonymous. Evaluation of fondaparinux (also called ARIXTRA) 2.5 mg subcutaneously once daily for the treatment of superficial thrombophlebitis (also known as superficial vein thrombosis). GlaxoSmithKline Clinical Trial Register 2013. [URL: www.gsk‐clinicalstudyregister.com/study/ART108053 (accessed 22 July 2014)]
    1. Decousus H, Prandoni P, Mismetti P, Bauersachs RM, Boda Z, Brenner B, et al. Fondaparinux for the treatment of superficial‐vein thrombosis in the legs. New England Journal of Medicine 2010;363(13):1222‐32. - PubMed
    1. Leizorovicz A, Becker F, Buchmuller A, Quere I, Prandoni P, Decousus H, et al. Clinical relevance of symptomatic superficial‐vein thrombosis extension: lessons from the CALISTO study. Blood 2013;122:1724‐9. - PubMed
Cho 2013 {published data only}
    1. Cho KY, Kim KI, Khurana S, Bae DK, Jin W. Is routine chemoprophylaxis necessary for prevention of venous thromboembolism following knee arthroplasty in a low incidence population?. Archives of Orthopaedic and Trauma Surgery 2013;133(4):551‐9. - PubMed
DRI4090 {published data only}
    1. Anon. A multicenter, randomized, double‐blind, placebo controlled, parallel group, dose response study of subcutaneous (Org31540/SR90107A) in the prevention of venous thromboembolism after elective total hip replacement surgery. GlaxoSmithKline Clinical Trial Register 2008. [URL: www.gsk‐clinicalstudyregister.com/study/DRI4090 (accessed 22 July 2014)]
    1. Fuji T, Fujita S, Ochi T. Fondaparinux prevents venous thromboembolism after joint replacement surgery in Japanese patients. International Orthopaedics 2008;32(4):443‐51. - PMC - PubMed
DRI4757 {published data only}
    1. Anonymous. A multicenter, randomized, double‐blind, placebo‐controlled, parallel group, dose response study of subcutaneous (Org31540/SR90107A) in the prevention of venous thromboembolism after elective total knee replacement surgery. GlaxoSmithKline Clinical Trial Register 2008; Vol. Study No.: DRI4757. [URL: http://www.gsk‐clinicalstudyregister.com/study/DRI4757?study_ids=DRI4757#rs (accessed 22 July 2014)]
    1. Fuji T, Fujita S, Ochi T. Fondaparinux prevents venous thromboembolism after joint replacement surgery in Japanese patients. International Orthopaedics 2008;32(4):443‐51. - PMC - PubMed
EFFORT {published data only}
    1. Steele KE, Canner J, Prokopowicz G, Verde F, Beselman A, Wyse R, et al. The EFFORT trial. Preoperative enoxaparin versus postoperative fondaparinux for thromboprophylaxis in bariatric surgical patients: a randomized double‐blind pilot trial. Surgery for Obesity and Related Diseases 2015;11(3):672‐83. - PubMed
EPHESUS {published data only}
    1. Anon. European Pentasaccharide Hip Elective Surgery Study (EPHESUS). A multicenter, randomized, double‐blind comparison of once daily subcutaneous (Org31540/SR90107A) with enoxaparin for the prevention of deep vein thrombosis or symptomatic pulmonary embolism in patients undergoing elective hip replacement surgery. GlaxoSmithKline Clinical Trial Register 2008. [URL: www.gsk‐clinicalstudyregister.com/study/63118 (accessed 22 July 2014)]
    1. Borja J, Olivella P, Curto J. Fondaparinux versus enoxaparin for prevention of venous thromboembolism. Lancet 2002;360(9345):1603‐4. - PubMed
    1. Lassen MR. Bauer K, Eriksson BI, Turpie AG, European Pentasaccharide Elective Surgery Study (EPHESUS) Steering Committee. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip‐replacement surgery: a randomised double‐blind comparison. Lancet 2002;359(9319):1715‐20. - PubMed
FONDACAST {published data only}
    1. Anon. FONDAparinux in patients with a plaster CAST (FONDACAST). GlaxoSmithKline Clinical Trial Register 2011. [URL: www.gsk‐clinicalstudyregister.com/study/109350 (accessed 22 July 2014)]
    1. Samama CM, Lecoules N, Kierzek G, Claessens YE, Riou B, Rosencher N, et al. Comparison of fondaparinux with low molecular weight heparin for venous thromboembolism prevention in patients requiring rigid or semi‐rigid immobilization for isolated non‐surgical below‐knee injury. Journal of Thrombosis and Haemostasis 2013;11(10):1833‐43. - PubMed
    1. Samama CM, Lecoules N, Kierzek G, Claessens YE, Riou B, Rosencher N, et al. Comparison of fondaparinux with low‐molecular‐weight heparin for venous thromboembolism prevention in patients requiring rigid or semi‐rigid immobilization for isolated non‐surgical below‐knee injury. Annales Francaises de Medecine d'Urgence 2014;4(3):153‐66. - PubMed
    1. Samama CM, Riou B, Roy P‐M, Sautet A, Mismetti P, FONDACAST Study Group. Prevention of venous thromboembolism after an isolated, non‐surgical below‐knee injury. Benefit/risk of fondaparinux vs. low molecular weight heparin: the Fondacast study. Journal of Thrombosis and Haemostasis 2013;11(Suppl S3):5. - PubMed
    1. Samama CMR. Subgroup analysis of the FONDACAST study comparing fondaparinux to low‐molecular‐weight heparin for the prevention of venous thromboembolism after an isolated, non‐surgical below‐knee injury. Journal of Thrombosis and Haemostasis 2013;11 (Suppl S2):88. - PubMed
Fuji 2015 {published and unpublished data}
    1. Fuji T, Fujita S, Kawai Y, Abe Y, Kimura T, Fukuzawa M, et al. A randomized, open‐label trial of edoxaban in Japanese patients with severe renal impairment undergoing lower‐limb orthopedic surgery. Thrombosis Journal 2015;13:6. [DOI: 10.1186/s12959-014-0034-9] - DOI - PMC - PubMed
Kolluri 2016 {published data only}
    1. Kolluri R, Plessa AL, Sanders MC, Singh NK, Lucore C. A randomized study of the safety and efficacy of fondaparinux versus placebo in the prevention of venous thromboembolism after coronary artery bypass graft surgery. American Heart Journal 2016;171(1):1‐6. - PubMed
L‐8541 {published data only}
    1. Anon. Arixtra VTE Prevention Study ‐ Fondaparinux compared with enoxaparin in the prevention of venous thromboembolism (VTE) in Chinese patients undergoing elective knee replacement, hip surgery or a revision of components. GlaxoSmithKline Clinical Trial Register 2008. [URL: www.gsk‐clinicalstudyregister.com/study/L‐8541 (accessed 22 July 2014)]
L‐8635 {published data only}
    1. Anon. Fondaparinux compared with enoxaparin in the prevention of venous thromboembolism in Taiwanese patients undergoing elective knee replacement. GlaxoSmithKline Clinical Trial Register 2008. [URL: www.gsk‐clinicalstudyregister.com/study/L‐8635 (accessed 22 July 2014)]
Li 2015 {published and unpublished data}
    1. Li B, Wang K, Zhao X, Lin C, Sun H. Comparison of fondaparinux sodium and low molecular weight heparin in the treatment of hypercoagulability secondary to traumatic infection. Chinese Journal of Traumatology 2015;18:147‐9. - PubMed
PEGASUS {published data only}
    1. Agnelli G, Bergqvist D, Cohen A, Gallus A, Gent M. A randomized double‐blind study to compare the efficacy and safety of fondaparinux with dalteparin in the prevention of venous thromboembolism after high‐risk abdominal surgery: the Pegasus study. Journal of Thrombosis and Haemostasis 2003; Vol. 1, issue Suppl 1:Abstract OC006.
    1. Agnelli G, Bergqvist D, Cohen A, Gallus AS, Gent M. A randomized double‐blind study to compare the efficacy and safety of postoperative fondaparinux (Arixtra) and preoperative dalteparin in the prevention of venous thromboembolism after high‐risk abdominal surgery: the PEGASUS study. Blood 2003;102(11 Pt 1):Abstract 40.
    1. Agnelli G, Bergqvist D, Cohen AT, Gallus AS, Gent M, PEGASUS Investigators. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high‐risk abdominal surgery. British Journal of Surgery 2005;92(10):1212‐20. - PubMed
    1. Anon. A multicenter, multinational, randomized, double‐blind study to compare the efficacy and safety of fondaparinux sodium (Org31540/SR90107A) with dalteparin (Fragmin) in the prevention of venous thromboembolic events in high‐risk abdominal surgery (PEGASUS). GlaxoSmithKline Clinical Trial Register 2005. [URL: www.gsk‐clinicalstudyregister.com/study/EFC3557 (accessed 22 July 2014)]
PENTAMAKS {published data only}
    1. Anon. A multicenter, multinational, randomized, double‐blind comparison of subcutaneous (Org31540/SR90107A) with enoxaparin in the prevention of deep vein thrombosis and symptomatic pulmonary embolism after elective major knee surgery or a revision (PENTAMAKS). GlaxoSmithKline Clinical Trial Register 2008. [URL: www.gsk‐clinicalstudyregister.com/study/095‐002 (accessed 22 July 2014)]
    1. Bauer K. The PENTAMAKS Study. Comparison of the first synthetic factor Xa inhibitor with low molecular weight heparin in the prevention of venous thromboembolism (VTE) after elective major knee surgery. Blood 2000;96:490a.
    1. Bauer KA, Eriksson BI, Lassen MR, Turpie AGG, for the Steering Committee of the Pentasaccharide in Major Knee Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. New England Journal of Medicine 2001;345(18):1305‐10. - PubMed
    1. Warkentin TE, Cook RJ, Marder VJ, Sheppard JA, Moore JC, Eriksson BI, et al. Anti‐platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin. Blood 2005;106(12):3791‐6. - PMC - PubMed
PENTATHLON {published data only}
    1. Turpie AG. Pentasaccharide (Org31540/SR90107A) clinical trials update: lessons for practice. American Heart Journal 2001;142(2 Suppl):S9‐15. - PubMed
    1. Turpie AG, Gallus AS, Hoek JA, Pentasaccharide Investigators. A synthetic pentasaccharide for the prevention of deep‐vein thrombosis after total hip replacement. New England Journal of Medicine 2001;344(9):619‐25. - PubMed
    1. Warkentin TE, Cook RJ, Marder VJ, Sheppard JI, Moore JC, Eriksson BI, et al. Anti‐platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin. Blood 2005;106(12):3791‐6. - PMC - PubMed
PENTATHLON 2000 {published data only}
    1. Anon. A multicenter, multinational, randomized, double‐blind comparison of subcutaneous (Org31540/SR90107A) with enoxaparin in the prevention of deep vein thrombosis and symptomatic pulmonary embolism after elective hip replacement or a revision. PENTATHLON 2000. GlaxoSmithKline Clinical Trial 2008. [URL: www.gsk‐clinicalstudyregister.com/study/EFC2442 (accessed 22 July 2014)]
    1. Turpie AG. The PENTATHALON 2000 Study: comparison of the first synthetic factor Xa inhibitor with low molecular weight heparin in the prevention of venous thromboembolism. Blood 2000;96(491A):Abstract A2112.
    1. Turpie AG, Bauer KA, Eriksson BI, Lassen MR, PENTATHALON 2000 Study Steering Committee. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip‐replacement surgery: a randomised double‐blind trial. Lancet 2002;359(9319):1721‐6. - PubMed
PENTHIFRA {published data only}
    1. Anon. A multicenter, multinational, randomized double‐blind comparison study of subcutaneous (Org31540/SR90107A) versus enoxaparin 40 mg o.d. in the prevention of deep vein thrombosis and symptomatic pulmonary embolism in hip fracture surgery (PENTHIFRA). GlaxoSmithKline Clinical Trial Register 2008. [URL: www.gsk‐clinicalstudyregister.com/study/EFC2698 (accessed 22 July 2014)]
    1. Eriksson B. The PENTHIFRA Study. Comparison of the first synthetic Factor Xa inhibitor with low molecular weight heparin (LMWH) for the prevention of venous thromboembolism (VTE) after hip fracture surgery. Blood 2000;96(490A):Abstract 2110.
    1. Eriksson BI, Bauer KA, Lassen MR, Turpie AGG, for the Steering Committee of the Pentasaccharide in Hip‐Fracture Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip‐fracture surgery. The New England Journal of Medicine 2001;345(18):1298‐304. - PubMed
PENTHIFRA PLUS {published data only}
    1. Anon. A multicenter, multinational, randomized, double‐blind study of fondaparinux sodium (Org31540/SR90107A) versus placebo for the prolonged prevention of VTE in hip fracture surgery (PENTIHFRA PLUS). GlaxoSmithKline Clinical Trial Register 2008. [URL: www.gsk‐clinicalstudyregister.com/study/EFC4582?study_ids=EFC4582#rs (accessed 22 July 2014)]
    1. Bauer KA, Eriksson BI, Lassen MR, Turpie AGG. No episode of thrombocytopenia after four‐week administration of fondaparinux, a new synthetic and selective inhibitor of factor Xa, in the PENTHIFRA‐PLUS study. Journal of Thrombosis and Haemostasis 2003;1(Suppl 1):P2050.
    1. Dobesh PP. Novel concepts: emerging data and the role of extended prophylaxis following hip fracture surgery. American Journal of Health‐System Pharmacy 2003;60(22 Suppl 7):S15‐9. - PubMed
    1. Eriksson BI. A multicenter, randomized, placebo‐controlled, double‐blind study of fondaparinux for the prolonged prevention of venous thromboembolism in hip fracture surgery. Abstracts of the Sicot/Sirot XXII World Congress 2002:318.
    1. Eriksson BI, Lassen MR. Consistency of efficacy of extended thromboprophylaxis with fondaparinux (Arixtra) in prevention of venous thromboembolism (VTE) after hip fracture surgery according to different composite efficacy endpoints: the PENTHIFRA‐PLUS study. Journal of Thrombosis and Haemostasis 2003;1(Suppl 1):Abstract P2064.
Shen 2014 {published and unpublished data}
    1. Shen Y, Zhong M, Tan L. Fondaparinux versus low molecular weight heparin following esophagectomy: results from a randomized and controlled trial. Chest 2014;145(3_Meeting Abstracts):535D.
Yokote 2011 {published data only}
    1. Yokote R, Matsubara M, Hirasawa N, Hagio S, Ishii K, Takata C. Is routine chemical thromboprophylaxis after total hip replacement really necessary in a Japanese population?. Journal of Bone and Joint Surgery British Volume 2011;93(2):251‐6. - PubMed

References to studies excluded from this review

ACT1840 {published data only}
    1. Anon. A multicentre pilot study of natural pentasaccharide (SR90107A /Org31540) for the prevention of deep venous thrombosis after total hip replacement. GlaxoSmithKline Clinical Trial Register 2008. [URL: www.gsk‐clinicalstudyregister.com/study/ACT1840 (accessed 22 July 2014)]
Amadeus 2008 {published data only}
    1. Amadeus Investigators, Bousser MG, Bouthier J, Büller HR, Cohen AT, Crijns H, Davidson BL, et al. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open‐label, non‐inferiority trial. Lancet 2008;371(9609):315‐21. [DOI: 10.1016/S0140-6736(08)60168-3] - DOI - PubMed
AR3106206 {published data only}
    1. Anon. Clinical evaluation of GSK576428 (fondaparinux sodium) in the treatment of acute pulmonary thromboembolism (PE). GlaxoSmithKline Clinical Trial Register 2009. [NCT00981409; URL: www.gsk‐clinicalstudyregister.com/study/106206?study_ids=AR3106206#ps (accessed 22 July 2014)]
AR3106333 {published data only}
    1. Anon. Clinical evaluation of GSK576428 (fondaparinux sodium) in prevention of venous thromboembolism after elective total hip replacement surgery. GlaxoSmithKline Clinical Trial Register 2008. [URL: http://www.gsk‐clinicalstudyregister.com/study/AR3106333?study_ids=AR3106333#ps (accessed 22 July 2014)]
AR3106335 {published data only}
    1. Anon. Clinical evaluation of GSK576428 (fondaparinux sodium) in prevention of venous thromboembolism after hip fracture surgery. GlaxoSmithKline Clinical Trial Register 2008. [NCT00320424; URL: http://www.gsk‐clinicalstudyregister.com/study/AR3106335?study_ids=AR3106335#ps (accessed 22 July 2014)]
Argun 2013 {published data only}
    1. Argun M, Oner M, Saglamoglu M, Karaman I, Guney A, Halici M, et al. Fondaparınux versus nadroparin for prevention of venous thromboembolism after elective hip and knee arthroplasty. Current Therapeutic Research 2013;74:49–53. - PMC - PubMed
Bonneux 2006 {published data only}
    1. Bonneux IM, Bellemans J, Fabry G. Evaluation of wound healing after total knee arthroplasty in a randomized prospective trial comparing fondaparinux with enoxaparin. Knee 2006;13(2):118‐21. - PubMed
Buller 2014 {published data only}
    1. Buller HR, Halperin J, Hankey GJ, Pillion G, Prins MH, Raskob GE. Comparison of idrabiotaparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: the Borealis‐Atrial Fibrillation Study. Journal of Thrombosis and Haemostasis 2014;12(6):824‐30. - PubMed
Cassiopea {published data only}
    1. Büller HR, Gallus AS, Pillion G, Prins MH, Raskob GE, on behalf of the Cassiopea Investigators. Enoxaparin followed by once‐weekly idrabiotaparinux versus enoxaparin plus warfarin for patients with acute symptomatic pulmonary embolism: a randomised, double‐blind, double‐dummy, non‐inferiority trial. Lancet 2012;379(9811):123‐9. - PubMed
Cohen 2007 {published data only}
    1. Cohen A, Brenkel I, Skinner J, Warwick D. Graduated compression stockings do not add to the efficacy of fondaparinux for thromboprophylaxis in hip replacement surgery. A multi‐centre, multi‐national, randomised, open‐label study. Journal of Bone and Joint Surgery British Volume 2009;91‐B(Suppl 1):73‐c.
    1. Cohen AT, Skinner JA, Warwick D, Brenkel I. The use of graduated compression stockings in association with fondaparinux in surgery of the hip. A multicentre, multinational, randomised, open‐label, parallel‐group comparative study. Journal of Bone and Joint Surgery British Volume 2007;89(7):887‐92. - PubMed
EQUINOX {published data only}
    1. The EQUINOX Invesstigators. Efficacy and safety of once weekly subcutaneous idrabiotaparinux in the treatment of patients with symptomatic deep venous thrombosis. Journal of Thrombosis and Haemostasis 2011;9(1):92‐9. - PubMed
extended van Gogh {published data only}
    1. van Gogh Investigators, Buller HR, Cohen AT, Davidson B, Decousus H, Gallus AS, et al. Extended prophylaxis of venous thromboembolism with idraparinux. New England Journal of Medicine 2007;357(11):1105‐12. - PubMed
FLEXTRA {published data only}
    1. Anon. Flexibility in administration of Arixtra for prevention of symptomatic venous thromboembolism in orthopedic surgery. GlaxoSmithKline Clinical Trial Register 2008. [URL: http://www.gsk‐clinicalstudyregister.com/study/L8518?study_ids=L851#rs (accessed 22 July 2014)]
    1. Colwell CW Jr, Kwong LM, Turpie AGG, Davidson BL. Flexibility in administration of fondaparinux for prevention of symptomatic venous thromboembolism in orthopaedic surgery. Journal of Arthroplasty 2006;21(1):36‐45. - PubMed
    1. Davidson BL, Turpie AGG, Kwong LM, Colwell CW. FLEXTRA: early vs delayed initiation of postoperative fondaparinux prophylaxis after joint replacement: a clinical outcome study. Journal of Thrombosis and Haemostasis 2005;3(Suppl 1):Abstract OR061.
Kawaji 2012 {published data only}
    1. Kawaji H, Ishii M, Tamaki Y, Hamasaki M, Ishikawa H, Sasaki K, et al. Postoperative prophylactic effect of fondaparinux for prevention of deep venous thrombosis after cemented total hip replacement:a comparative study. Modern Rheumatology / The Japan Rheumatism Association 2012;22(2):216–22. - PubMed
Li 2013 {published data only}
    1. Li MW, Zhao XM, Rao LX. The clinical efficacy and safety of fondaparinux combined with tirofiban hydrochloride in patients with acute coronary syndrome undergoing complex percutaneous coronary intervention. Zhonghua Nei Ke Za Zhi 2013;52:1037‐40. - PubMed
MATISSE‐DVT {published data only}
    1. Buller HR, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, et al. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Annals of Internal Medicine 2004;140(11):867‐73. - PubMed
MATISSE‐PE {published data only}
    1. The Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. New England Journal of Medicine 2003;349(18):1695‐702. - PubMed
NCT00521885 {published data only}
    1. NCT00521885. Comparison of arixtra vs. lovenox to prevent blood clots in medically ill patients (BRiEF). ClinicalTrials.gov 2007. [URL: http://clinicaltrials.gov/show/NCT00521885 (accessed 8 March 2016)]
NCT00539942 {published data only}
    1. NCT00539942. Study of arixtra to prevent blood clots in women undergoing abdominopelvic surgery for likely gynecologic malignancy. ClinicalTrials.gov. [URL: http://clinicaltrials.gov/ct2/show/NCT00539942 (accessed 8 March 2016)]
PENTATAK {published data only}
    1. Anon. A multicenter, concurrent control, randomized, open‐label, assessor‐blind, dose‐ranging study (of Org 31540/SR90107A) in the prophylaxis of deep vein thrombosis in subjects undergoing total knee replacement surgery (PENTATAK). GlaxoSmithKline Clinical Trial Register 2008. [URL: www.gsk‐clinicalstudyregister.com/study/95001 (accessed 23 July 2014)]
PERSIST {published data only}
    1. PERSIST Investigators. A novel long‐acting synthetic factor Xa inhibitor (SanOrg34006) to replace warfarin for secondary prevention in deep vein thrombosis. A phase II evaluation. Journal of Thrombosis and Haemostasis 2004;2(1):47‐53. - PubMed
Rembrandt {published data only}
    1. The Rembrandt Investigators. Treatment of proximal deep vein thrombosis with a novel synthetic compound (SR90107A/ Org31540) with pure anti‐factor Xa activity. A phase II evaluation. Circulation 2000;102:2726‐31. - PubMed
SAFE‐AF {published data only}
    1. Cohen A, Stellbrink C, Heuzey JY, Faber T, Aliot E, Banik N, et al. Safety of fondaparinux in transoesophageal echocardiography‐guided electric cardioversion of atrial fibrillation (SAFE‐AF) study: a pilot study. Archives of Cardiovascular Diseases 2014;108:122‐31. - PubMed
Sasaki 2009 {published data only}
    1. Sasaki S, Miyakoshi N, Matsuura H, Saitoh H, Kudoh D, Shimada Y. Prospective randomized controlled trial on the effect of fondaparinux sodium for prevention of venous thromboembolism after hip fracture surgery. Journal of Orthopaedic Science 2009;14(5):491‐6. - PubMed
Sasaki 2011 {published data only}
    1. Sasaki S, Miyakoshi N, Matsuura H, Saito H, Nakanishi T, Kudo Y, et al. Prospective study on the efficacies of fondaparinux and enoxaparin in preventing venous thromboembolism after hip fracture surgery. Journal of Orthopaedic Science 2011;16(1):64‐70. - PubMed
Savi 2005 {published data only}
    1. Savi P, Chong BH, Greinacher A, Gruel Y, Kelton JG, Warkentin TE, et al. Effect of fondaparinux on platelet activation in the presence of heparin‐dependent antibodies: a blinded comparative multicenter study with unfractionated heparin. Blood 2005;105(1):139‐44. - PubMed
Tsutsumi 2012 {published data only}
    1. Tsutsumi S, Yajima R, Tabe Y, Takaaki T, Fujii F, Morita H, et al. The efficacy of fondaparinux for the prophylaxis of venous thromboembolism after resection for colorectal cancer. Hepatogastroenterology 2012;59:2477‐9. - PubMed
van Gogh‐DVT {published data only}
    1. van Gogh Investigators, Buller HR, Cohen AT, Davidson B, Decousus H, Gallus AS, et al. Idraparinux versus standard therapy for venous thromboembolic disease. New England Journal of Medicine 2007;357(11):1094‐104. - PubMed
van Gogh‐PE {published data only}
    1. van Gogh Investigators. Idraparinux versus standard therapy for venous thromboembolic disease. New England Journal of Medicine 2007;357(11):1094‐104. - PubMed
Xin 2013 {published data only}
    1. Xin Z, Ya‐Ling H, Xiao‐Zeng W, Bai‐Ge X. Efficacy and safety of fondaparinux during thrombolytic therapy in acute ST elevation myocardial infarction patients. Heart 2013;99:A54‐A55.
Yamaoka 2014 {published data only}
    1. Yamaoka YI, Nishikawa T. The impact of fondaparinux on the prophylaxis of venous thromboembolism: the efficacy, safety and prognosis after resection for colorectal cancer. Annals of Surgical Oncology. 2014; Vol. 21, issue 1 Suppl 1.
Zhao 2013 {published data only}
    1. Zhao X, Han Y, Wang X, Xu B. Efficacy and safety of fondaparinux during thrombolytic therapy in acute ST elevation myocardial infarction patients. Cardiology (Switzerland) 2013;126:138.
Zhao 2015 {published data only}
    1. Zhao XM, Gao CY, Chu YJ. Fondaparinux vs. enoxaparin in patients with non‐ST elevation acute coronary syndromes (NSTE‐ACS) treated with percutaneous coronary intervention and tirofiban: an exploratory study in China. Journal of Clinical Pharmacy and Therapeutics 2015;40:584‐9. - PubMed

References to ongoing studies

EUCTR2007‐003746‐15‐DE {published data only}
    1. EUCTR2007‐003746‐15‐DE. Prospective randomized open study on the comparison of fondaparinux with the low‐molecular‐weight heparin enoxaparin in patients undergoing femoro‐distal venous bypass operation. WHO International Clinical Trials Registry 2008. [URL: http://apps.who.int/trialsearch/Trial.aspx?TrialID=EUCTR2007‐003746‐15‐DE (accessed 19 September 2016)]
EUCTR2008‐001779‐31‐IT {published data only}
    1. Markers of hypercoagulability and risk of death and rehospitalization in heart failure patients: a pilot study on the effects of Fondaparinux ‐ Fondaparinux and heart failure. WHO International Clinical Trials Registry. [URL : http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2008‐001779‐31‐IT (accessed 19 September 2016)]
JPRN‐UMIN000002444 {published data only}
    1. JPRN‐UMIN000002444. Randomized study of anti‐coagulant therapy to prevent postoperative deep venous thrombosis/pulmonary embolism. WHO International Clinical Trials Registry 2009. [URL: http://apps.who.int/trialsearch/trial.aspx?trialid=JPRN‐UMIN000002444 (accessed 19 September 2016)]
JPRN‐UMIN000007005 {published data only}
    1. JPRN‐UMIN000007005. The efficacy and safety of anticoagulant therapy Arixtra Injection for the prevention of the vein thromboembolism in laparoscopic colorectal surgery. WHO International Clinical Trials Registry 2011. [URL: http://apps.who.int/trialsearch/Trial.aspx?TrialID=JPRN‐UMIN000007005 (accessed 19 September 2016)]
JPRN‐UMIN000008435 {published data only}
    1. Phase III study of efficacy of fondaparinux on the prevention of post‐operative venous thromboembolism in patients undergoing with laparoscopic colorectal cancer surgery. WHO International Clinical Trials Registry. [URL: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=JPRN‐UMIN000008435 (accessed 19 September 2016)]
PROTECT {published data only}
    1. NCT00881088. Prophylaxis of thromboembolic complications trial: thromboprophylaxis needed in below knee plaster cast immobilization for ankle and foot fractures (PROTECT). ClinicalTrials.gov 2009. [URL: http://clinicaltrials.gov/ct2/show/NCT00881088?term=NCT00881088&rank=1 (accessed 8 March 2016)]

Additional references

Ageno 2012
    1. Ageno W, Riva N, Noris P, Nisio M, Regina M, Arioli D, et al. The FONDAIR Study Group. Safety and efficacy of low dose fondaparinux (1.5 mg) for the prevention of venous thromboembolism in acutely ill medical patients with renal impairment: the FONDAIR study. Journal of Thrombosis and Haemostasis 2012;10(11):2291‐7. - PubMed
Agnelli 2000
    1. Agnelli G, Sonaglia F. Prevention of venous thromboembolism. Thrombosis Research 2000;97(1):V49‐62. - PubMed
Amiral 1997
    1. Amiral J, Lormeau JC, Marfaing‐Koka A, Vissac AM, Wolf M, Boyer‐Neumann C, et al. Absence of cross‐reactivity of SR90107A/ORG31540 pentasaccharide with antibodies to heparin‐PF4 complexes developed in heparin‐induced thrombocytopenia. Blood Coagulation and Fibrinolysis 1997;8(2):114‐7. - PubMed
Atkins 2004
    1. Atkins D, Best D, Briss PA, Eccles M, Falck‐Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. British Medical Journal 2004;328(7454):1490‐4. - PMC - PubMed
Bauer 2003
    1. Bauer KA. New pentasaccharides for prophylaxis of deep vein thrombosis: pharmacology. Chest 2003;124(6 Suppl):364s‐70s. - PubMed
Bauersachs 2005
    1. Bauersachs RM. Fondaparinux: an update on new study results. European Journal of Clinical Investigation 2005;35(Suppl 1):27‐32. - PubMed
Bergqvist 2006
    1. Bergqvist D. Review of fondaparinux sodium injection for the prevention of venous thromboembolism in patients undergoing surgery. Vascular Health and Risk Management 2006;2(4):365‐70. - PMC - PubMed
Bounameaux 2002
    1. Bounameaux H, Perneger T. Fondaparinux: a new synthetic pentasaccharide for thrombosis prevention. Lancet 2002;359(9319):1710‐1. - PubMed
Brito 2011
    1. Brito V, Ciapponi A, Kwong J. Factor Xa inhibitors for acute coronary syndromes. Cochrane Database of Systematic Reviews 2011, Issue 1. [DOI: 10.1002/14651858.CD007038.pub2] - DOI - PubMed
Delavenne 2010
    1. Delavenne X, Zufferey P, Baylot D, Nguyen P, Borg JY, Fontenay M, et al. Population pharmacokinetics of fondaparinux administered at prophylactic doses after major orthopaedic surgery in everyday practice. Thrombosis and Haemostasis 2010;104(2):252‐60. - PubMed
Delavenne 2012
    1. Delavenne X, Zufferey P, Nguyen P, Rosencher N, Samama CM, Bazzoli C, et al. Pharmacokinetics of fondaparinux 1.5 mg once daily in a real‐world cohort of patients with renal impairment undergoing major orthopaedic surgery. European Journal of Clinical Pharmacology 2012;68(10):1403‐10. - PubMed
Erkens 2010
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