Long-term Treatment Of Venous Thromboembolism Research Articles

PB0500 Edoxaban for Acute and Long-Term Treatment of Venous Thromboembolism: Real-Life Data from a Single Center Cohort Study

PB0500 Edoxaban for Acute and Long-Term Treatment of Venous Thromboembolism: Real-Life Data from a Single Center Cohort Study

Long-term VTE treatment with rivaroxaban: Results from the DRESDEN NOAC REGISTRY

Data on long-term effectiveness and safety of venous thromboembolism (VTE) treatment with rivaroxaban are scarce and not available from randomized clinical trials. To supplement the positive results of phase III VTE treatment trials with rivaroxaban, we used data from the ongoing, prospective, non-interventional DRESDEN NOAC REGISTRY to evaluate long-term management patterns and clinical outcomes.Between December 1st 2011 and September 30th 2020, 812 patients with acute VTE (575 DVT; 237 PE) and rivaroxaban treatment were prospectively followed. During treatment (median rivaroxaban exposure 1.1 years IQR 0.3–5.0 years; median follow-up 6.1 years IQR 4.7–7.8 years) rates of recurrent VTE and ISTH major bleeding were 0.7/100 pt. years (95% CI 0.4–1.1) and 2.1/100 pt. years; 95% CI 1.5–2.8, respectively. Of the 427 patients still taking rivaroxaban at 12 months, 276 and 202 were still taking rivaroxaban at 3 and 5 years, respectively. “Scheduled end of treatment” was the leading discontinuation reason also beyond 12 months. When exposure days were divided by the number of major clinical outcomes (recurrent VTE + other major cardiovascular + ISTH major bleeding), continued rivaroxaban treatment had the longest “exposure per event” period (6398 days/event) compared to patients switching to alternative treatments (4658 days/event) or stopping anticoagulation completely (4337 days/event).Our results confirm low thrombotic and major bleeding rates for long-term VTE treatment with rivaroxaban. Beyond 12 months, scheduled treatment discontinuations still occur. Although 3–5% of patients planned for indefinite rivaroxaban therapy switched to other anticoagulants each year, the overall persistence to rivaroxaban was high.

Current Recommendations for the Management of Cancer-Associated Venous Thromboembolism

Abstract Cancer-associated thrombosis (CAT) is a major cause of death in oncological patients. The mechanisms of thrombogenesis in cancer patients are not fully established, and it seems to be multifactorial in origin. Also, several risk factors for venous thromboembolism (VTE) are present in these patients such as tumor site, stage, histology of cancer, chemotherapy, surgery, and immobilization. Anticoagulant treatment in CAT is challenging because of high bleeding risk during treatment and recurrence of VTE. Current major guidelines recommend low molecular weight heparins (LMWHs) for early and long-term treatment of VTE in cancer patients. In the past years, direct oral anticoagulants (DOACs) are recommended as potential treatment option for VTE and have recently been proposed as a new option for treating CAT. This manuscript will give a short overview of risk factors involved in the development of CAT and a summary on the recent recommendations and guidelines for treatment of VTE in patients with malignancies, discussing also some special clinical situations (e.g. renal impairment, catheter-related thrombosis, and thrombocytopenia).

Treatment of venous thromboembolism in patients with cancer: from clinical trials to real life

Approximately one-fifth of all cases of venous thromboembolism (VTE) are related to cancer. VTE complications may have a substantial impact on prognosis, quality of life and care in patients with cancer. Patients with cancer-related VTE are at increased risk of developing recurrent VTE compared to patients without cancer, but also have a higher risk of major bleeding. In the last years, direct oral anticoagulants (DOACs) have been evaluated in a head-to-head comparison with low molecular weight heparin (LMWH) in two randomized trials for the long-term treatment of VTE in patients with advanced cancer. The results of these trials show that DOACs have a similar efficacy profile, but probably higher risk of bleeding, compared to LMWH dalteparin. Because DOACs offer a simple oral treatment regimen without the need for anticoagulation monitoring, they could be attractive alternatives to LMWHs in these setting. The American Society of Clinical Oncology guidelines, published in August 2019, recommend LMWH, edoxaban and rivaroxaban as first-choice therapies for long-term anticoagulation in cancer patients with VTE. However, several practical issues should be considered concerning the long-term use of DOAC treatment in patients with cancer. Major concerns have been highlighted about the gastrointestinal bleeding risk in patients with gastrointestinal cancers and the potential drug-drug interactions in combination for some specific anticancer therapies. Several studies comparing DOACs with LMWH are currently ongoing to refine our knowledge concerning treatment with DOACs in patients with cancer-associated VTE.

Bemiparin as a long-term treatment for venous thrombosis in cancer patients: the ELEBAMA study.

Low-molecular-weight heparin (LMWH) is the standard treatment for cancer-associated venous thromboembolism (VTE). There have been no specific studies evaluating bemiparin for VTE in people with cancer. The aim of this study is to evaluate the effects of bemiparin for long-term treatment of VTE in routine clinical practice. Prospective observational study. Consecutive patients with active cancer and VTE, under treatment with bemiparin for at least 6 months, were recruited. We included 89 patients. The 6- and 9-month cumulative VTE recurrence rates were 2.4% and 5.9%, respectively. The 6-month cumulative rate of major bleeding was 1.3%, and of clinically relevant non-major bleeding, 8%. The incidence of events in this study is lower than that reported in randomized trials. Bemiparin is effective and safe for the long-term treatment of cancer-associated VTE in routine clinical practice.

A Retrospective Study on Efficacy and Safety of Rivaroxaban and Dalteparin for Long-Term Treatment of Venous Thromboembolism in Patients with Lung Cancer

Background: Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear. Objectives: We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer. Methods: A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality. Results: The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595–2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624–1.196, p = 0.337). Conclusions: There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.

Direct oral anticoagulants in patients with venous thromboembolism and thrombophilia: a systematic review and meta‐analysis

Essentials We investigated direct oral anticoagulant (DOAC) use in venous thromboembolism and thrombophilia. A comprehensive search identified 10 studies, 8 of which were included in a meta-analysis. DOACs were overall safe and effective in patients with venous thromboembolism and thrombophilia. Efficacy/safety of DOACs was maintained in low-risk antiphospholipid syndrome patient subgroup. SUMMARY: Background Direct oral anticoagulants (DOACs) are increasingly used in acute and long-term treatment of venous thromboembolism (VTE). However, their role in management of thrombophilia-associated VTE is controversial. Methods Through a comprehensive search on MEDLINE, Cochrane Library, and Clinicaltrials.gov, we identified 10 eligible studies, 8 of which reporting data on 1994 thrombophilia patients were included in a random-effects meta-analysis. Eligible studies were phase 2 to 3 randomized controlled trials comparing DOACs to vitamin K antagonists (VKAs) in patients with VTE, including those with thrombophilia. Results Of eight studies included in meta-analysis, four evaluated rivaroxaban, three dabigatran, and one edoxaban. No results could be obtained on apixaban use. The rates of VTE recurrence (RR, 0.70; 95% CI, 0.34-1.44; I2 =0%) and major/clinically relevant non-major bleeding events (RR, 0.92; 95% CI, 0.62-1.36; I2 =23%) were similar between thrombophilia patients treated with DOACs compared to VKAs. Results were comparable to findings in patients without known thrombophilia: RR, 1.02; 95% CI, 0.80-1.30; I2 =46% for VTE recurrence and RR, 0.72; 95% CI, 0.57-0.90; I2 =84% for major/clinically relevant non-major bleeding events. Conclusions Rates of VTE recurrence and bleeding events were both low and comparable in patients with various thrombophilias receiving either treatment, suggesting that DOACs are an appropriate treatment option in this population. Due to limited data, it is unclear whether these findings apply to specific subgroups such as high-risk antiphospholipid syndrome, uncommon thrombophilias, or the use of apixaban.

Bleeding in patients receiving non-vitamin K oral anticoagulants: clinical trial evidence

In optimizing anticoagulation therapy, it is essential to balance treatment efficacy with the major adverse effect of anticoagulant treatment, bleeding risk. This narrative review examines the efficacy and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban compared with standard anticoagulation or placebo. NOAC therapies provide equivalent to superior protection versus standard therapy, with similar or superior safety, and potential benefits in convenience. We will review the phase III evidence for each of the available NOACs in different antithrombotic indications, including atrial fibrillation (in the absence of significant mitral stenosis or mechanical heart valves); prophylaxis of venous thromboembolism (VTE) in patients undergoing orthopedic surgery; and acute and long-term treatment of VTE. Further, we will illustrate scenarios in which the evidence is stronger for a particular agent in the context of the overall positive safety and efficacy profile of NOACs in general. Limitations of the factor Xa inhibitors include the lack of a specific antidote in case of a bleeding emergency (an approved agent is available for reversing the effect of the direct thrombin inhibitor). We discuss the options for mitigating bleeding and describe the ongoing developments towards specific reversal agents. In conclusion, the available data for efficacy and safety, together with reliable pharmacokinetics obviating the need for regular monitoring, indicate that NOACs may offer substantial benefits for patients with nonvalvular atrial fibrillation or VTE.

Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer.

Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer.

A Review of the Role of Non-Vitamin K Oral Anticoagulants in the Acute and Long-Term Treatment of Venous Thromboembolism.

Venous thromboembolism (VTE), which includes both deep vein thrombosis and pulmonary embolism (PE), is a very common disorder with high risk for recurrence and is associated with significant morbidity and mortality. The non-vitamin K oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban, and edoxaban, have been shown to be noninferior to conventional anticoagulant therapy for the prevention of recurrent VTE and are associated with more favorable bleeding risk. Evidence from the treatment of VTE with traditional therapy (low molecular weight heparin and vitamin K antagonists) implies that extended or indefinite treatment reduces risk of recurrence. Recently, mounting evidence suggests a role for the extended use of NOACs to reduce the risk of VTE recurrence. This review summarizes the existing evidence for the extended use of NOACs in the treatment of VTE from phase III extension studies with dabigatran, rivaroxaban, and apixaban. Additionally, it examines and discusses the major society guidelines and how these recommendations may change physician practices in the near future.

The Role of Tinzaparin in Oncology

Current guidelines recommend low-molecular-weight heparin treatment in patients with cancer with established venous thromboembolism (VTE). The aim of this article was to study the pharmacological properties and effectiveness of tinzaparin in patients with cancer as well as its potential anticancer properties. A search of PubMed and ScienceDirect databases up to March 2016 was carried out to identify published studies that detect the properties and use of tinzaparin in oncology. Protamine sulfate partially (60% to 65%) neutralized tinzaparin’s anti-Xa activity. No dose adjustment of tinzaparin is needed even in patients with severe renal impairment and Creatinine Clearance ≥20 mL/min. Tinzaparin demonstrated a statistically significant decline in VTE recurrence at 1 year post the index thromboembolic event. A statistically significant reduction in minor bleeding rates was also described, whereas major bleeding events did not decrease in patients with cancer treated with tinzaparin versus those who received vitamin K antagonists. Tinzaparin treatment in patients suffering from deep vein thrombosis reduced the incidence of postthrombotic syndrome and venous ulcers. Tinzaparin’s ability to prevent both metastatic dissemination of cancer cells and tumor angiogenesis has been delineated in preclinical research. Current data show that tinzaparin is safe and efficacious either for short-term or for long-term treatment of VTE in patients with cancer. Clinical trials are needed in order to examine the utility of tinzaparin in primary prevention of VTE and validate its potential anticancer advantages exhibited in preclinical research.

Tinzaparin for Long-Term Treatment of Venous Thromboembolism in Patients With Cancer: A Systematic Review and Meta-Analysis.

Patients with cancer are at increased risk of recurrent venous thromboembolism (VTE) and bleeding. Thus, long-term treatment with anticoagulants for secondary prevention is challenging. The objective of this review was to evaluate current evidence on the safety and efficacy of tinzaparin compared with other anticoagulants for long-term VTE treatment in patients with cancer. Based on a preregistered protocol, we identified randomized controlled trials (RCTs) comparing long-term tinzaparin (therapeutic dose: 175 IU/kg) versus other anticoagulants for at least 3 months after an acute episode of VTE that included adult patients with underlying malignancy. We extracted predefined, clinically relevant outcomes of patients with cancer and, using standard methodology, pooled available data and assessed risk of bias and quality of evidence for each study. Three open-label RCTs evaluating 1169 patients with cancer were included in the analysis. Tinzaparin was associated with a significantly lower risk of recurrent VTE at the end of treatment (relative risk [RR], [95% confidence interval] 0.67 [0.46-0.99]) and at longest follow-up (RR: 0.58 [0.39-0.88]) and showed a lower risk of clinically relevant non-major bleeding at the end of treatment (RR: 0.71 [0.51-1.00]). No significant between-treatment differences were found for all-cause mortality (RR: 1.09 [0.91-1.30]) or fatal and non-fatal major bleeding events (RR: 1.06 [0.56-1.99]). The overall quality of evidence was deemed moderate, mainly due to small sample size in 2 of the studies and limited number of events in the meta-analyses. In conclusion, both short- and long-term treatments with tinzaparin were found to be superior to vitamin K antagonists for avoiding recurrences of VTE.

Prophylaxis and treatment of venous thromboembolism based on Japanese clinical guides.

Venous thromboembolism (VTE) has recently increased owing to the westernization of our food habits and an aging society in Japan. The Japanese Guidelines for VTE Prophylaxis were formulated and issued in 2004 and then revised in 2009. The incidence rates of symptomatic perioperative pulmonary thromboembolism (PTE) in Japan are being investigated by the Japanese Society of Anesthesiologists since 2002. The average rate of perioperative PTE was estimated to be 3.1 per 10,000 operations between 2002 and 2011. However, this rate significantly declined after the guidelines for thromboprophylaxis were issued and the management fee for PTE prophylaxis was covered by a health insurance in 2004. The average mortality rate was 17.9%, but it significantly decreased after new anticoagulants were approved in 2008. An anticoagulant, which is effective for both acute and long-term VTE treatment, is clearly beneficial and avoids the need for any form of overlapping therapy. The emerging oral antithrombotic compounds such as direct oral anticoagulants (DOACs), which have the potential to inhibit factor Xa, do not require laboratory monitoring. The oral administration of DOACs results in a benefit-to-risk ratio that is at least comparable with that provided by a conventional treatment with heparin followed by vitamin K antagonists.

Safety ad efficacy of direct oral anticoagulants for extended treatment of venous thromboembolism

Currently available anticoagulants have limitations for long-term treatment of venous thromboembolism (VTE). We have evaluated the efficacy and safety of direct oral anticoagulants (DOACs) for extended treatment of VTE. Four randomized controlled trials (RCTs) comparing DOACs (apixaban, rivaroxaban, and dabigatran) with placebo or warfarin for extended treatment of VTE were published. Primary efficacy outcome was recurrent VTE or VTE-related death, and primary safety outcome was major bleeding. DOACs significantly lower the risk of recurrent VTE or VTE-related death compared to placebo/warfarin, as well as all-cause mortality. Risk of major bleeding is not different with DOACs compared to placebo/warfarin. However, DOACs are associated with a significantly higher rate of the composite of major and clinically relevant bleeding compared to placebo. In conclusion, DOACs are effective and safe for the extended treatment of VTE, and may reduce the risk of all-cause mortality.

Practice Patterns for Prophylaxis and Treatment of Venous Thromboembolism in German Cancer Patients

Background: Venous thromboembolism (VTE) is a serious threat for cancer patients. Guidelines recommend low-molecular-weight heparin (LMWH) for prophylaxis and treatment, but it is unknown to what extent specialists adhere to these recommendations. This survey assesses the current approach to patients with cancer-associated VTE in Germany. Materials and Methods: A questionnaire was sent out to members of the DGHO (Deutsche Gesellschaft für Hämatologie und Onkologie), the BNHO (Berufsverband Niedergelassener Hämatologen und Onkologen) and the DGP (Deutsche Gesellschaft für Phlebologie). For most questions, more than 1 answer was possible; therefore, the total sum of percentages may exceed 100%. Results: 275 specialists responded. 76% of them treat acute VTE with LMWH while 22% switch to oral treatments (vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs)) during the acute phase. For the next 3-6 months, 55% of the specialists continue LMWH, while 31% switch to VKAs and 33% to NOACs. Among those who continue LMWH for 3-6 months, 37% continue at the full dose, 26% reduce to 75% of the initial dose, and 40% even to 50%. Important factors guiding treatment decisions were the need for injections and the availability of a partner/spouse (LMWH), the need for laboratory controls (VKAs), and the number of other oral medications (NOACs). Conclusion: This survey reveals that practice patterns often do not follow the guideline recommendations with respect to the use of LMWH for long-term treatment of VTE in cancer patients.

Use of statins and reduced risk of recurrence of VTE in an older population. A population-based cohort study.

We aimed to determine whether statin use is associated with a decreased risk of recurrent venous thromboembolism (VTE) in older patients. We used a pre-assembled cohort of patients at least 65 years of age diagnosed with incident VTE between January 1, 1994 and December 31, 2004 in the province of Québec, Canada and followed until December 31, 2005. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) of recurrent VTE associated with current and past use of statins, compared with non-use. The cohort included 25,681 patients with incident VTE. During a mean follow-up of 3.0 years, there were 2343 recurrent VTE events (rate: 3.1 per 100 person-years). Compared with non-use, current use of statins was associated with a decreased risk of VTE recurrence (rates: 1.55 vs 3.47 per 100 per year, respectively; HR: 0.74, 95 % CI: 0.61-0.89), while no association was observed with past use (HR: 0.98, 95 % CI: 0.76-1.25). In a secondary analysis, longer durations of statin use were associated with greater risk reductions (0-6 months, HR 0.82, 95 % CI: 0.67-1.01; 6-12 months, HR 0.62, 95 % CI: 0.43-0.90; ≥ 12 months, HR: 0.50, 95 % CI: 0.33-0.74; p-value for trend ≤ 0.001). The use of statin was associated with a decreased risk of recurrent VTE in older patients. This study supports the need for randomised controlled trials to assess the efficacy and safety of statins in the long-term treatment of VTE.

Improving Awareness and Outcomes Related to Venous Thromboembolism.

Improving Awareness and Outcomes Related to Venous Thromboembolism.

Trousseau's syndrome: cancer-associated thrombosis.

Trousseau's syndrome (cancer-associated thrombosis) is the second leading cause of death in cancer patients, after death from cancer itself. The risk of a venous thromboembolism is 4- to 7-fold higher in patients with cancer than in those without cancer. The causes of this impaired coagulation are associated with general patient-related risk factors, and other factors that are specific to the particular cancer or treatment. It is important to assess the risk of thrombotic events in cancer patients and administer effective prophylaxis and treatment. Effective prophylaxis and treatment of venous thromboembolism reduces morbidity and mortality, and improves patients' quality of life. Low molecular weight heparin is the first-line treatment for venous thromboembolism, as an effective and safe means for prophylaxis and treatment, according to guidelines released by international scientific societies. Oral anticoagulation therapy with warfarin is preferable to no therapy. However, warfarin has low efficacy and is associated with high rates of recurrence. If low molecular weight heparin is unavailable, some guidelines recommend the use of vitamin K antagonists that have a target international normalized ratio in the range of 2-3, as acceptable alternatives. Novel oral anticoagulants that directly inhibit factor Xa or thrombin are promising for the prophylaxis of high-risk cancer patients and in the long-term treatment of venous thromboembolism. However, to date, there is insufficient evidence to support the use of these new anticoagulants.

Prophylaxis and treatment of venous thromboembolism in patients with cancer: the Saudi clinical practice guideline.

BACKGROUND AND OBJECTIVESVenous thromboembolism (VTE) is commonly encountered in the daily clinical practice. Cancer is an important VTE risk factor. Proper thromboprophylaxis is key to prevent VTE in patients with cancer, and proper treatment is essential to reduce VTE complications and adverse events associated with the therapy.DESIGN AND SETTINGSAs a result of an initiative of the Ministry of Health of Saudi Arabia, an expert panel led by the Saudi Association for Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the Saudi Scientific Hematology Society with the methodological support of the McMaster University working group produced this clinical practice guideline to assist health care providers in evidence-based clinical decision-making for VTE prophylaxis and treatment in patients with cancer.METHODSSix questions related to thromboprophylaxis and antithrombotic therapy were identified and the corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.RESULTSQuestion 1Should heparin versus no heparin be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation?RecommendationFor outpatients with cancer, the Saudi Expert Panel suggests against routine thromboprophylaxis with heparin (weak recommendation; moderate quality evidence).Question 2Should oral anticoagulation versus no oral anticoagulation be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation?RecommendationFor outpatients with cancer, the Saudi Expert Panel recommends against thromboprophylaxis with oral anticoagulation (strong recommendation; moderate quality evidence).Question 3Should parenteral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters?RecommendationFor outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests thromboprophylaxis with parenteral anticoagulation (weak recommendation; moderate quality evidence).Question 4Should oral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters?RecommendationFor outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests against thromboprophylaxis with oral anticoagulation (weak recommendation; low quality evidence).Question 5Should low-molecular-weight heparin versus unfractionated heparin be used in patients with cancer being initiated on treatment for venous thromboembolism?RecommendationIn patients with cancer being initiated on treatment for venous thromboembolism, the Saudi Expert Panel suggests low-molecular-weight heparin over intravenous unfractionated heparin (weak; very low quality evidence).Question 6Should heparin versus oral anticoagulation be used in patients with cancer requiring long-term treatment of VTE?RecommendationIn patients with metastatic cancer requiring long-term treatment of VTE, the Saudi Expert Panel recommends low-molecular-weight heparin (LMWH) over vitamin K antagonists (VKAs) (strong recommendation; moderate quality evidence). In patients with non-metastatic cancer requiring long-term treatment of venous thromboembolism, the Saudi Expert Panel suggests LMWH over VKA (weak recommendation; moderate quality evidence).

Fondaparinux in the initial and long-term treatment of venous thromboembolism

BackgroundEven 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. MethodsWe used the Registro Informatizado de Enfermedad Tromboembólica (RIETE) registry to compare the rate of VTE recurrences and major bleeding at 10 and 90days 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 ResultsOf 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 3months 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). ConclusionsAn 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.