A placebo-controlled trial assessed the efficacy of rivaroxaban to prevent venous thrombosis in patients with cancer at high risk for thrombosis. The thrombosis rate was lower with rivaroxaban, but ...for the 180-day assessment period, the difference was not significant. Bleeding was approximately twice as common in the rivaroxaban group.
Background: Guidelines addressing the management of venous thromboembolism (VTE) in cancer patients are heterogeneous and their implementation has been suboptimal worldwide. Objectives: To establish ...a common international consensus addressing practical, clinically relevant questions in this setting. Methods: An international consensus working group of experts was set up to develop guidelines according to an evidence‐based medicine approach, using the GRADE system. Results: For the initial treatment of established VTE: low‐molecular‐weight heparin (LMWH) is recommended 1B; fondaparinux and unfractionated heparin (UFH) can be also used 2D; thrombolysis may only be considered on a case‐by‐case basis Best clinical practice (Guidance); vena cava filters (VCF) may be considered if contraindication to anticoagulation or pulmonary embolism recurrence under optimal anticoagulation; periodic reassessment of contraindications to anticoagulation is recommended and anticoagulation should be resumed when safe; VCF are not recommended for primary VTE prophylaxis in cancer patients Guidance. For the early maintenance (10 days to 3 months) and long‐term (beyond 3 months) treatment of established VTE, LMWH for a minimum of 3 months is preferred over vitamin K antagonists (VKA) 1A; idraparinux is not recommended 2C; after 3–6 months, LMWH or VKA continuation should be based on individual evaluation of the benefit‐risk ratio, tolerability, patient preference and cancer activity Guidance. For the treatment of VTE recurrence in cancer patients under anticoagulation, three options can be considered: (i) switch from VKA to LMWH when treated with VKA; (ii) increase in LMWH dose when treated with LMWH, and (iii) VCF insertion Guidance. For the prophylaxis of postoperative VTE in surgical cancer patients, use of LMWH o.d. or low dose of UFH t.i.d. is recommended; pharmacological prophylaxis should be started 12–2 h preoperatively and continued for at least 7–10 days; there are no data allowing conclusion that one type of LMWH is superior to another 1A; there is no evidence to support fondaparinux as an alternative to LMWH 2C; use of the highest prophylactic dose of LMWH is recommended 1A; extended prophylaxis (4 weeks) after major laparotomy may be indicated in cancer patients with a high risk of VTE and low risk of bleeding 2B; the use of LMWH for VTE prevention in cancer patients undergoing laparoscopic surgery may be recommended as for laparotomy Guidance; mechanical methods are not recommended as monotherapy except when pharmacological methods are contraindicated 2C. For the prophylaxis of VTE in hospitalized medical patients with cancer and reduced mobility, we recommend prophylaxis with LMWH, UFH or fondaparinux 1B; for children and adults with acute lymphocytic leukemia treated with l‐asparaginase, depending on local policy and patient characteristics, prophylaxis may be considered in some patients Guidance; in patients receiving chemotherapy, prophylaxis is not recommended routinely 1B; primary pharmacological prophylaxis of VTE may be indicated in patients with locally advanced or metastatic pancreatic 1B or lung 2B cancer treated with chemotherapy and having a low risk of bleeding; in patients treated with thalidomide or lenalidomide combined with steroids and/or chemotherapy, VTE prophylaxis is recommended; in this setting, VKA at low or therapeutic doses, LMWH at prophylactic doses and low‐dose aspirin have shown similar effects; however, the efficacy of these regimens remains unclear 2C. Special situations include brain tumors, severe renal failure (CrCl < 30 mL min−1), thrombocytopenia and pregnancy. Guidances are provided in these contexts. Conclusions: Dissemination and implementation of good clinical practice for the management of VTE, the second cause of death in cancer patients, is a major public health priority.
Background: Although long‐term indwelling central venous catheters (CVCs) may lead to pulmonary embolism (PE) and loss of the CVC, there is lack of consensus on management of CVC‐related thrombosis ...(CRT) in cancer patients and heterogeneity in clinical practices worldwide. Objectives: To establish common international Good Clinical Practices Guidelines (GCPG) for the management of CRT in cancer patients. Methods: An international working group of experts was set up to develop GCPG according to an evidence‐based medicine approach, using the GRADE system. Results: For the treatment of established CRT in cancer patients, we found no prospective randomized studies, two non‐randomized prospective studies and one retrospective study examining the efficacy and safety of low‐molecular‐weight heparin (LMWH) plus vitamin K antagonists (VKAs). One retrospective study evaluated the benefit of CVC removal and two small retrospective studies were on thrombolytic drugs. For the treatment of symptomatic CRT, anticoagulant treatment (AC) is recommended for a minimum of 3 months; in this setting, LMWHs are suggested. VKAs can also be used, in the absence of direct comparisons of these two types of anticoagulants in this setting Guidance. The CVC can be kept in place if it is functional, well‐positioned and non‐infected and there is good resolution under close surveillance; whether the CVC is kept or removed, no standard approach in terms of AC duration has been established Guidance. For the prophylaxis of CRT in cancer patients, we found six randomized studies investigating the efficacy and safety of VKA vs. placebo or no treatment, one on the efficacy and safety of unfractionnated heparin, six on the value of LMWH, one double‐blind randomized and one non randomized study on thrombolytic drugs and six meta‐analyses of AC and CVC thromboprophylaxis. Type of catheter (open‐ended like the Hickman® catheter vs. closed‐ended catheter with a valve like the Groshong® catheter), its position (above, below or at the junction of the superior vena cava and the right atrium) and method of placement may influence the onset of CRT on the basis of six retrospective trials, four prospective non‐randomized trials, three randomized trials and one meta‐analysis. In light of these data: use of AC for routine prophylaxis of CRT is not recommended 1A; a CVC should be inserted on the right side, in the jugular vein, and distal extremity of the CVC should be located at the junction of the superior vena cava and the right atrium 1A. Conclusion: Dissemination and implementation of these international GCPG for the prevention and treatment of CRT in cancer patients at each national level is a major public health priority, needing worldwide collaboration.
Summary
Background
Treatment of venous thromboembolism (VTE) in patients with cancer has a high rate of recurrence and bleeding complications. Guidelines recommend low‐molecular‐weight heparin (LMWH) ...for at least 3–6 months and possibly indefinitely for patients with active malignancy. There are, however, few data supporting treatment with LMWH beyond 6 months. The primary aim of the DALTECAN study (NCT00942968) was to determine the safety of dalteparin between 6 and 12 months in cancer‐associated VTE.
Methods
Patients with active cancer and newly diagnosed VTE were enrolled in a prospective, multicenter study and received subcutaneous dalteparin for 12 months. The rates of bleeding and recurrent VTE were evaluated at months 1, 2–6 and 7–12.
Findings
Of 334 patients enrolled, 185 and 109 completed 6 and 12 months of therapy; 49.1% had deep vein thrombosis (DVT); 38.9% had pulmonary embolism (PE); and 12.0% had both on presentation. The overall frequency of major bleeding was 10.2% (34/334). Major bleeding occurred in 3.6% (12/334) in the first month, and 1.1% (14/1237) and 0.7% (8/1086) per patient‐month during months 2–6 and 7–12, respectively. Recurrent VTE occurred in 11.1% (37/334); the incidence rate was 5.7% (19/334) for month 1, 3.4% (10/296) during months 2–6, and 4.1% (8/194) during months 7–12. One hundred and sixteen patients died, four due to recurrent VTE and two due to bleeding.
Conclusion
Major bleeding was less frequent during dalteparin therapy beyond 6 months. The risk of developing major bleeding complications or VTE recurrence was greatest in the first month of therapy and lower over the subsequent 11 months.
In this study involving nearly 3400 patients with venous thromboembolism, both prophylactic and therapeutic doses of rivaroxaban were superior to aspirin in reducing the risk of recurrent ...thromboembolism with a similar risk of bleeding.
Venous thromboembolism, which includes deep-vein thrombosis and pulmonary embolism, is the third most common cause of vascular death after myocardial infarction and stroke.
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The mainstay of treatment is anticoagulation,
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and in patients without active cancer, guidelines suggest the use of direct oral anticoagulant agents such as rivaroxaban over vitamin K antagonists such as warfarin.
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Anticoagulation therapy is administered for 3 months or longer, depending on the balance between the risk of recurrent venous thromboembolism and the risk of bleeding.
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In patients without reversible risk factors, the risk of recurrent venous thromboembolism is as much as 10% in the first . . .
In this comparative-effectiveness trial, the oral direct thrombin inhibitor dabigatran was shown to be as effective as warfarin in the prevention of recurrent venous thromboembolism. Bleeding ...complications were similar. Dabigatran therapy offers the advantage that monitoring of anticoagulation is not necessary.
In this comparative-effectiveness trial, the oral direct thrombin inhibitor dabigatran was shown to be as effective as warfarin in the prevention of recurrent venous thromboembolism. Dabigatran therapy offers the advantage that monitoring of anticoagulation is not necessary.
Venous thromboembolism affects 1 to 2 adults per 1000 annually and is the third most common cause of vascular death after myocardial infarction and stroke.
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The current standard treatment is rapidly acting parenteral anticoagulation for 5 to 7 days followed by at least 3 months of treatment with a vitamin K antagonist.
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Treatment with a vitamin K antagonist requires frequent monitoring of the international normalized ratio (INR), and multiple interactions of vitamin K antagonists with foods and other drugs have been reported.
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Dabigatran etexilate (hereafter termed dabigatran) is an orally available, potent, direct inhibitor of thrombin. It is rapidly . . .
Dabigatran and warfarin have been compared for the treatment of acute venous thromboembolism (VTE) in a previous trial. We undertook this study to extend those findings.
In a randomized, ...double-blind, double-dummy trial of 2589 patients with acute VTE treated with low-molecular-weight or unfractionated heparin for 5 to 11 days, we compared dabigatran 150 mg twice daily with warfarin. The primary outcome, recurrent symptomatic, objectively confirmed VTE and related deaths during 6 months of treatment occurred in 30 of the 1279 dabigatran patients (2.3%) compared with 28 of the 1289 warfarin patients (2.2%; hazard ratio, 1.08; 95% confidence interval CI, 0.64-1.80; absolute risk difference, 0.2%; 95% CI, -1.0 to 1.3; P<0.001 for the prespecified noninferiority margin for both criteria). The safety end point, major bleeding, occurred in 15 patients receiving dabigatran (1.2%) and in 22 receiving warfarin (1.7%; hazard ratio, 0.69; 95% CI, 0.36-1.32). Any bleeding occurred in 200 dabigatran (15.6%) and 285 warfarin (22.1%; hazard ratio, 0.67; 95% CI, 0.56-0.81) patients. Deaths, adverse events, and acute coronary syndromes were similar in both groups. Pooled analysis of this study RE-COVER II and the RE-COVER trial gave hazard ratios for recurrent VTE of 1.09 (95% CI, 0.76-1.57), for major bleeding of 0.73 (95% CI, 0.48-1.11), and for any bleeding of 0.70 (95% CI, 0.61-0.79).
Dabigatran has similar effects on VTE recurrence and a lower risk of bleeding compared with warfarin for the treatment of acute VTE.
www.clinicaltrials.gov. Unique identifiers: NCT00680186 and NCT00291330.
Summary Background Information about the variation in the risk for venous thromboembolism (VTE) and in prophylaxis practices around the world is scarce. The ENDORSE (Epidemiologic International Day ...for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting) study is a multinational cross-sectional survey designed to assess the prevalence of VTE risk in the acute hospital care setting, and to determine the proportion of at-risk patients who receive effective prophylaxis. Methods All hospital inpatients aged 40 years or over admitted to a medical ward, or those aged 18 years or over admitted to a surgical ward, in 358 hospitals across 32 countries were assessed for risk of VTE on the basis of hospital chart review. The 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines were used to assess VTE risk and to determine whether patients were receiving recommended prophylaxis. Findings 68 183 patients were enrolled; 30 827 (45%) were categorised as surgical, and 37 356 (55%) as medical. On the basis of ACCP criteria, 35 329 (51·8%; 95% CI 51·4–52·2; between-country range 35·6–72·6) patients were judged to be at risk for VTE, including 19 842 (64·4%; 63·8–64·9; 44·1–80·2) surgical patients and 15 487 (41·5%; 41·0–42·0; 21·1–71·2) medical patients. Of the surgical patients at risk, 11 613 (58·5%; 57·8–59·2; 0·2–92·1) received ACCP-recommended VTE prophylaxis, compared with 6119 (39·5%; 38·7–40·3; 3·1–70·4) at-risk medical patients. Interpretation A large proportion of hospitalised patients are at risk for VTE, but there is a low rate of appropriate prophylaxis. Our data reinforce the rationale for the use of hospital-wide strategies to assess patients' VTE risk and to implement measures that ensure that at-risk patients receive appropriate prophylaxis.
Patients with advanced cancer are at increased risk for venous thrombosis and thromboembolism related to both the effects of cancer and its treatment. In this study, semuloparin was shown to reduce ...the incidence of thromboembolism without affecting the risk of major bleeding.
Venous thromboembolism, a common complication in patients with cancer,
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results in increased morbidity, mortality, medical care, and cost.
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In addition to surgery
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and prolonged hospital stays,
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chemotherapy is increasingly recognized as a risk factor for venous thromboembolism in patients with cancer.
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The risk of venous thromboembolism in patients receiving chemotherapy for cancer is dependent on many contributing factors, including the site and stage of the primary cancer, type and intensity of the chemotherapeutic regimen, age, coexisting conditions, and Eastern Cooperative Oncology Group (ECOG) performance status.
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Evidence from randomized, controlled trials concerning the clinical benefit of antithrombotic prophylaxis . . .
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