Fondaparinux for the treatment of superficial vein thrombosis in the legs

Producción CientíficaThe efficacy and safety of anticoagulant treatment for patients with acute, symptom- atic superf icial-vein thrombosis in the legs, but without concomitant deep-vein thrombosis or symptomatic pulmonary embolism at presentation, have not been es- tablished. Methods In a randomized, double-blind trial, we assigned 3002 patients to receive either fonda- parinux, administered subcutaneously at a dose of 2.5 mg once daily, or placebo for 45 days. The primary eff icacy outcome was a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep-vein thrombosis, or symp- tomatic extension to the saphenofemoral junction or symptomatic recurrence of superf icial-vein thrombosis at day 47. The main safety outcome was major bleeding. The patients were followed until day 77. Results The primary eff icacy outcome occurred in 13 of 1502 patients (0.9%) in the fonda- parinux group and 88 of 1500 patients (5.9%) in the placebo group (relative risk reduction with fondaparinux, 85%; 95% conf idence interval [CI], 74 to 92; P<0.001). The incidence of each component of the primary efficacy outcome was significantly reduced in the fondaparinux group as compared with the placebo group, except for the outcome of death (0.1% in both groups). The rate of pulmonary embolism or deep-vein thrombosis was 85% lower in the fondaparinux group than in the pla- cebo group (0.2% vs. 1.3%; 95% CI, 50 to 95; P<0.001). Similar risk reductions were observed at day 77. A total of 88 patients would need to be treated to prevent one instance of pulmonary embolism or deep-vein thrombosis. Major bleeding occurred in one patient in each group. The incidence of serious adverse events was 0.7% with fondaparinux and 1.1% with placebo. Conclusions Fondaparinux at a dose of 2.5 mg once a day for 45 days was effective in the treat- ment of patients with acute, symptomatic superf icial-vein thrombosis of the legs and did not have serious side effects. (Funded by GlaxoSmithKline; ClinicalTrials .gov number, NCT00443053.

Use of the Delphi method to facilitate antithrombotics prescription during pregnancy.

International audienceINTRODUCTION: Management of pregnant women at risk for venous thromboembolism (VTE) remains complex. Guidelines do not definitively fix optimal strategies due to limited trial data. Our objective was to build an easy-to-use tool allowing individualised, risk-adapted prophylaxis. MATERIALS AND METHODS: A Delphi exercise was conducted to collect 19 French experts' opinions on pregnancy-related VTE. RESULTS: Experts with an active interest in clinical research and care of VTE and placental vascular complications were selected. The risk score was classified by an anonymous computer vote. A scoring system for VTE risk in pregnant women was developed, each score being associated with a specific treatment: graduated elastic compression stockings, aspirin, prophylactic Low Molecular Weight Heparin (LMWH: variable durations), or adjusted-dose of LMWH through pregnancy and postpartum. CONCLUSIONS: Our simple consensual scoring system offers an individual estimation of thrombosis risk during pregnancy together with its related therapeutic strategy, in accordance with most of the new international recommendations. The accuracy of our individual risk score-based therapeutic guidance is currently being prospectively evaluated in a multicenter trial

Survival effects of inferior vena cava filter in patients with acute symptomatic venous thromboembolism and a significant bleeding risk.

OBJECTIVES The purpose of this study was to investigate the survival effects of inferior vena cava filters in patients with venous thromboembolism (VTE) who had a significant bleeding risk. BACKGROUND The effectiveness of inferior vena cava filter use among patients with acute symptomatic VTE and known significant bleeding risk remains unclear. METHODS In this prospective cohort study of patients with acute VTE identified from the RIETE (Computerized Registry of Patients With Venous Thromboembolism), we assessed the association between inferior vena cava filter insertion for known significant bleeding risk and the outcomes of all-cause mortality, pulmonary embolism (PE)-related mortality, and VTE rates through 30 days after the initiation of VTE treatment. Propensity score matching was used to adjust for the likelihood of receiving a filter. RESULTS Of the 40,142 eligible patients who had acute symptomatic VTE, 371 underwent filter placement because of known significant bleeding risk. A total of 344 patients treated with a filter were matched with 344 patients treated without a filter. Propensity score-matched pairs showed a nonsignificant trend toward lower risk of all-cause death for filter insertion compared with no insertion (6.6% vs. 10.2%; p = 0.12). The risk-adjusted PE-related mortality rate was lower for filter insertion than no insertion (1.7% vs. 4.9%; p = 0.03). Risk-adjusted recurrent VTE rates were higher for filter insertion than for no insertion (6.1% vs. 0.6%; p < 0.001). CONCLUSIONS In patients presenting with VTE and with a significant bleeding risk, inferior vena cava filter insertion compared with anticoagulant therapy was associated with a lower risk of PE-related death and a higher risk of recurrent VTE. However, study design limitations do not imply a causal relationship between filter insertion and outcome

Outcomes Associated With Inferior Vena Cava Filters Among Patients With Thromboembolic Recurrence During Anticoagulant Therapy.

OBJECTIVES The aim of this study was to assess the effectiveness of inferior vena cava (IVC) filter use among patients who develop recurrent symptomatic venous thromboembolism (VTE) on anticoagulant therapy. BACKGROUND There is a lack of efficacy evidence of IVC filter therapy in patients with VTE recurrence on anticoagulant therapy. METHODS In this cohort study of patients with acute VTE identified from the RIETE (Registro Informatizado de la Enfermedad Tromboembólica) registry, the associations between IVC filter placement for VTE recurrence in the first 3 months of anticoagulant therapy and the outcomes of all-cause mortality, pulmonary embolism (PE)-related mortality, second recurrent VTE, and major bleeding rates through 30 days after diagnosis of recurrence were assessed. RESULTS Among 17 patients treated with filters and 49 matched patients treated without filters for VTE recurrence that presented as deep vein thrombosis, propensity score-matched groups showed no significant differences in death for filter insertion compared with no insertion (17.7% vs. 12.2%; p = 0.56). Among 48 patients treated with filters and 91 matched patients treated without filters for VTE recurrence that presented as PE, propensity score-matched groups showed a significant decrease in all-cause death for filter insertion compared with no insertion (2.1% vs. 25.3%; p = 0.02). The PE-related mortality rate was not significantly lower for filter insertion than no insertion (2.1% vs. 17.6%; p = 0.08), though the point estimates markedly differed. CONCLUSIONS Among patients with VTE recurrence during the first 3 months of anticoagulant therapy, IVC filter insertion was not associated with a survival benefit in patients who recurred with deep vein thrombosis, although it was associated with a lower risk for all-cause death in patients who recurred with PE

Idraparinux versus standard therapy in the treatment of deep venous thrombosis in cancer patients: A subgroup analysis of the Van Gogh DVT trial

Standard treatment with heparin followed by vitamin K antagonists is frequently complicated by bleeding and recurrent venous thromboembolism (VIE) in cancer patients with VTE. To compare the efficacy, safety and overall survival of long-term idraparinux treatment to standard therapy in cancer patients we conducted a post-hoc analysis in the subgroup of non-active and active cancer patients included in the Van Gogh DVT clinical trial. The cancer patients with deep venous thrombosis (DVT) and without pulmonary embolism (PE) were randomised to standard treatment or a once-weekly subcutaneous injection of idraparinux (2.5 mg), a synthetic pentasaccharide. 421 cancer patients were included. A total of 220 patients received idraparinux and 201 were allocated to standard therapy for three months (8%) or six months (92%). A recurrent VTE was observed during the first six months in 2.5% (n=5) of the idraparinux recipients compared to 6.4% (n=12) in the standard therapy group (hazard ratio 0.39, 95% confidence interval [Cl]; 0.14-1.11). The rate of bleeding was comparable (odds ratio 0.89, 95% Cl; 0.50-1.59). The outcomes were similar at three months after randomisation in all patients. Of the idraparinux recipients, 22.7% (n=50) died during the study period compared to 48 patients (23.9%) in the standard treatment group (hazard ratio 0.99, 95% Cl; 0.66-1.48). In conclusion, no significant safety or survival differences were observed between cancer patients with DVT treated with idraparinux for six months compared to standard therapy. Fewer recurrent VTEs were observed in the idraparinux group; however, this was not statistically significant and also because of study limitations this should be interpreted with cautio

Outcomes Associated With Inferior Vena Cava Filters Among Patients With Thromboembolic Recurrence During Anticoagulant Therapy

OBJECTIVES The aim of this study was to assess the effectiveness of inferior vena cava (IVC) filter use among patients who develop recurrent symptomatic venous thromboembolism (VTE) on anticoagulant therapy. BACKGROUND There is a lack of efficacy evidence of IVC filter therapy in patients with VTE recurrence on anticoagulant therapy. METHODS In this cohort study of patients with acute VTE identified from the RIETE (Registro Informatizado de la Enfermedad Tromboembólica) registry, the associations between IVC filter placement for VTE recurrence in the first 3 months of anticoagulant therapy and the outcomes of all-cause mortality, pulmonary embolism (PE)-related mortality, second recurrent VTE, and major bleeding rates through 30 days after diagnosis of recurrence were assessed. RESULTS Among 17 patients treated with filters and 49 matched patients treated without filters for VTE recurrence that presented as deep vein thrombosis, propensity score-matched groups showed no significant differences in death for filter insertion compared with no insertion (17.7% vs. 12.2%; p = 0.56). Among 48 patients treated with filters and 91 matched patients treated without filters for VTE recurrence that presented as PE, propensity score-matched groups showed a significant decrease in all-cause death for filter insertion compared with no insertion (2.1% vs. 25.3%; p = 0.02). The PE-related mortality rate was not significantly lower for filter insertion than no insertion (2.1% vs. 17.6%; p = 0.08), though the point estimates markedly differed. CONCLUSIONS Among patients with VTE recurrence during the first 3 months of anticoagulant therapy, IVC filter insertion was not associated with a survival benefit in patients who recurred with deep vein thrombosis, although it was associated with a lower risk for all-cause death in patients who recurred with PE

Low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy: Rationale and design of the High-low study, a randomised trial of two doses

Women with a history of venous thromboembolism (VTE) have a 2% to 10% absolute risk of VTE recurrence during subsequent pregnancies. Therefore, current guidelines recommend that all pregnant women with a history of VTE receive pharmacologic thromboprophylaxis. The optimal dose of low-molecular-weight heparin (LMWH) for thromboprophylaxis is unknown. In the Highlow study (NCT 01828697; www.highlowstudy.org), we compare a fixed low dose of LMWH with an intermediate dose of LMWH for the prevention of pregnancy-associated recurrent VTE. We present the rationale and design features of this study. The Highlow study is an investigator-initiated, multicentre, international, open-label, randomised trial. Pregnant women with a history of VTE and an indication for ante- and postpartum pharmacologic thromboprophylaxis are included before 14weeks of gestation. The primary efficacy outcome is symptomatic recurrent VTE during pregnancy and 6weeks postpartum. The primary safety outcomes are clinically relevant bleeding, blood transfusions before 6weeks postpartum and mortality. Patients are closely monitored to detect cutaneous reactions to LMWH and are followed for 3months after delivery. A central independent adjudication committee adjudicates all suspected outcome events. The Highlow study is the first large randomised controlled trial in pregnancy that will provide high-quality evidence on the optimal dose of LWMH thromboprophylaxis for the prevention of recurrent VTE in pregnant women with a history of VT

Low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy: Rationale and design of the High-low study, a randomised trial of two doses

BACKGROUND: Women with a history of venous thromboembolism (VTE) have a 2% to 10% absolute risk of VTE recurrence during subsequent pregnancies. Therefore, current guidelines recommend that all pregnant women with a history of VTE receive pharmacologic thromboprophylaxis. The optimal dose of low-molecular-weight heparin (LMWH) for thromboprophylaxis is unknown. In the Highlow study (NCT 01828697; www.highlowstudy.org), we compare a fixed low dose of LMWH with an intermediate dose of LMWH for the prevention of pregnancy-associated recurrent VTE. We present the rationale and design features of this study. METHODS: The Highlow study is an investigator-initiated, multicentre, international, open-label, randomised trial. Pregnant women with a history of VTE and an indication for ante- and postpartum pharmacologic thromboprophylaxis are included before 14weeks of gestation. The primary efficacy outcome is symptomatic recurrent VTE during pregnancy and 6weeks postpartum. The primary safety outcomes are clinically relevant bleeding, blood transfusions before 6weeks postpartum and mortality. Patients are closely monitored to detect cutaneous reactions to LMWH and are followed for 3months after delivery. A central independent adjudication committee adjudicates all suspected outcome events. CONCLUSION: The Highlow study is the first large randomised controlled trial in pregnancy that will provide high-quality evidence on the optimal dose of LWMH thromboprophylaxis for the prevention of recurrent VTE in pregnant women with a history of VTE.publisher: Elsevier articletitle: Low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy: Rationale and design of the Highlow study, a randomised trial of two doses journaltitle: Thrombosis Research articlelink: http://dx.doi.org/10.1016/j.thromres.2016.06.001 content_type: article copyright: © 2016 Elsevier Ltd. All rights reserved.status: publishe

Risk of recurrent venous thromboembolism according to baseline risk factor profiles

The optimal duration of anticoagulation for venous thromboembolism (VTE) is uncertain. In this prespecified analysis, we used data from 2 randomized trials, which compared once-daily rivaroxaban (20 mg or 10 mg) with aspirin (100 mg) or placebo for extended VTE treatment to estimate the risk of recurrence according to baseline risk factor profiles. Index VTE events were centrally classified as unprovoked, or provoked by major transient or persistent, or minor transient or persistent risk factors, and rates of recurrence at 1 year were calculated. A total of 2832 patients received rivaroxaban; 1131 received aspirin, and 590 received placebo. With unprovoked VTE, rates of recurrence in the 1173 patients given rivaroxaban, the 468 given aspirin, and the 243 given placebo were 2.0%, 5.9%, and 10.0%, respectively. There were no recurrences in patients with VTE provoked by major transient risk factors. With VTE provoked by minor persistent risk factors, recurrence rates in the 1184 patients given rivaroxaban, the 466 given aspirin, and the 248 given placebo were 2.4%, 4.5%, and 10.7%, respectively. For patients with minor transient risk factors, recurrence rates were 0.4% in the 268 patients given rivaroxaban, 4.2% in the 121 given aspirin, and 7.1% in the 56 given placebo. Recurrence rates in patients with VTE provoked by minor persistent or minor transient risk factors were not significantly lower than that with unprovoked VTE (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.56-1.16; and HR, 0.68; 95% CI, 0.32-1.30, respectively). Therefore, such patients may also benefit from extended anticoagulation therapy