Highlights
- •We evaluated the outcome of long-term therapy with fondaparinux in VTE patients.
- •The 10-day outcome was similar to that of patients treated with heparins.
- •The 90-day outcome was similar to that of cancer patients treated with LMWHs.
- •A 90-day high major bleeding rate was observed in non-cancer fondaparinux patients.
- •No relevant conclusions can be derived on the few enrolled cancer patients.
Abstract
Background
Even in the absence of evidence on its long-term efficacy and safety, a number of
patients with venous thromboembolism (VTE) receive long-term therapy with fondaparinux
alone in everyday practice.
Methods
We used the Registro Informatizado de Enfermedad Tromboembólica (RIETE) registry to
compare the rate of VTE recurrences and major bleeding at 10 and 90 days in patients with and without cancer. For long-term therapy, fondaparinux was
compared with vitamin K antagonists (VKA) in patients without cancer and with low-molecular-weight
heparin (LMWH) in those with cancer Results
Of 47,378 patients recruited, 46,513 were initially treated with heparin, 865 with
fondaparinux. Then, 263 patients (78 with cancer) were treated for at least 3 months with fondaparinux. After propensity-score matching, there were no differences
between patients receiving initial therapy with heparin or fondaparinux. Among patients
with cancer, there were no differences between fondaparinux and LMWH. Among patients
without cancer, the long-term use of fondaparinux was associated with an increased
risk of major bleeding (3.24 % vs. 0.95 %, p < 0.05).
Conclusions
An unexpected high rate of major bleeding was observed in non-cancer patients treated
with long-term fondaparinux. Our small sample does not allow to derive relevant conclusions
on the use of fondaparinux in cancer patients.
Abbreviations:
VTE (venous thromboembolism), LMWH (low molecular weight heparin), UFH (unfractioned heparin), VKA (vitamin k antagonists), RIETE (Registro Informatizado de Enfermedad TromboEmbólica), DVT (deep vein thrombosis), PE (pulmonary embolism), CUS (compressive ultrasonography), IU (international units), SD (standard deviation), CrCl (creatinine clearance), CI (confidence intervals)Keywords
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References
- Anticoagulant drugs in the treatment of pulmonary embolism A controlled trial.Lancet. 1960; 1: 1309-1312
- Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal vein thrombosis.N Engl J Med. 1992; 327: 1485-1489https://doi.org/10.1056/NEJM199211193272103
- A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism Duration of Anticoagulation Trial Study Group.N Engl J Med. 1995; 332: 1661-1665https://doi.org/10.1056/NEJM199506223322501
- A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency.Arch Intern Med. 2000; 160: 181-188https://doi.org/10.1001/archinte.160.2.181
- Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism.N Engl J Med. 2003; 349: 1695-1702https://doi.org/10.1056/NEJMoa03545
- Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial.Ann Intern Med. 2004; 140: 867-873https://doi.org/10.7326/0003-4819-140-11-200406010-0000
- Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism.Cochrane Database Syst Rev. 2010; 9: CD001100https://doi.org/10.1002/14651858.CD001100.pub3
- Influence of preceding duration of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping therapy: analysis of individual participants’ data from seven trials.BMJ. 2011; 342: d3036https://doi.org/10.1136/bmj.d3036
- 2008 French national guidelines for the treatment of venous thromboembolism in patients with cancer: report from the working group.Crit Rev Oncol Hematol. 2010; 73: 31-46https://doi.org/10.1016/j.critrevonc.2008.12.004
- Antithrombotic therapy for VTE disease. Antithrombotic therapy and prevention of thrombosis (9th Edition): American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2012; 141: e419S-e494Shttps://doi.org/10.1378/chest.11-2301
- Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline Update.J Clin Oncol. 2013; 31: 2189-2204https://doi.org/10.1200/JCO.2013.49.1118
- Low molecular weight heparin versus acenocoumarol in the secondary prophylaxis of deep vein thrombosis.Thromb Haemost. 1999; 81 ([PubMed PMID: 9974369]): 26-31
- Low molecular weight heparin versus oral anticoagulants in the long term treatment of deep venous thrombosis.J Vasc Surg. 2001; 33: 77-90https://doi.org/10.1067/mva.2001.109336
- Comparison of low molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study.Arch Intern Med. 2002; 162: 1729-1735https://doi.org/10.1001/archinte.162.15.1729
- Vitamin K antagonists or low-molecular-weight heparin for the long-term treatment of symptomatic venous thromboembolism.Cochrane Database Syst Rev. Oct 17 2012; 10: CD002001https://doi.org/10.1002/14651858.CD002001.pub2
- Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.N Engl J Med. 2003; 349: 146-153https://doi.org/10.1056/NEJMoa025313
- Low-molecular-weight heparin for the long-term treatment of symptomatic venous thromboembolism: meta-analysis of the randomized comparisons with oral anticoagulants.J Thromb Haemost. 2003; 1 (PubMed PMID: 12941030): 1906-1913
- How I, treat venous thromboembolism in patients with cancer.Blood. 2005; 106: 4027-4033https://doi.org/10.1182/blood-2005-04-1508
- Secondary prevention of venous thromboembolic events in patients with active cancer: enoxaparin alone versus initial enoxaparin followed by warfarin for a 180-day period.Clin Appl Thromb Hemost. 2006; 12: 389-396https://doi.org/10.1177/1076029606293692
- Self-managed long-term low-molecular-weight heparin therapy: the balance of benefits and harms.Am J Med. 2007; 120: 72-82https://doi.org/10.1016/j.amjmed.2006.03.030
- Home therapy of venous thrombosis with long-term LMWH versus usual care: patient satisfaction and post-thrombotic syndrome.Am J Med. 2009; 122: 762-769https://doi.org/10.1016/j.amjmed.2008.12.023
- A randomised open-label trial comparing long-term sub-cutaneous low molecular- weight heparin compared with oral-anticoagulant therapy in the treatment of deep venous thrombosis.Eur J Vasc Endovasc Surg. 2009; 37: 349-356https://doi.org/10.1016/j.ejvs.2008.11.030
- Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer.Cochrane Database Syst Rev. Jun 19 2014; 6: CD006649https://doi.org/10.1002/14651858.CD006649.pub6
- Fondaparinux - data on efficacy and safety in special situations.Thromb Res. Apr 2012; 129: 407-417https://doi.org/10.1016/j.thromres.2011.10.037
- Pentasaccharides in the prophylaxis and treatment of venous thromboembolism: a systematic review.Curr Opin Pulm Med. Sep 2004; 10 ([PubMed PMID: 15316429]): 338-344
- Computerized registry of patients with thromboembolic disease in Spain (RIETE): background, objectives, methods, and preliminary results.Rev Clin Esp. Feb 2003; 203 ([PubMed PMID: 12605778]): 68-73
- The outcome after treatment of venous thromboembolism is different in surgical and acutely ill medical patients. Findings from the RIETE registry.J Thromb Haemost. Nov 2004; 2: 1892-1898https://doi.org/10.1111/j.1538-7836.2004.01012.x
- A simple approach for detection of recurrent proximal vein thrombosis.Circulation. 1993; 88: 1730-1735https://doi.org/10.1161/01.CIR.88.4.1730
- Fatal pulmonary embolism and fatal bleeding in cancer patients with venous thromboembolism: findings from the RIETE registry.J Thromb Haemost. 2006; 4: 1950-1956https://doi.org/10.1111/j.1538-7836.2006.02082.x
- Predicting recurrences or major bleeding in cancer patients with venous thromboembolism. Findings from the RIETE Registry.Thromb Haemost. 2008; 100: 435-439https://doi.org/10.1160/TH08-02-0125
- Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group.Stat Med. 1998; 17: 2265-2281https://doi.org/10.1002/(SICI)1097-0258(19981015)17:19<2265::AID-SIM918>3.0.CO;2-B
- Propensity score matching in SPSS.([Accessed June 16, 2014. arXiv:1201.6385 [stat.AP].])
- FondaKIDS II: Long-term Follow-up Data of Children Receiving Fondaparinux for Treatment of Venous Thromboembolic Events.Thromb Res. 2014; 134: 643-647https://doi.org/10.1016/j.thromres.2014.07.026
Article info
Publication history
Published online: December 12, 2014
Accepted:
November 30,
2014
Received in revised form:
October 24,
2014
Received:
August 28,
2014
Identification
Copyright
© 2014 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.