Treatment with dabigatran or warfarin in patients with venous thromboembolism and cancer

Summary The efficacy and safety of dabigatran for treatment of venous thromboembolism (VTE) were demonstrated in two trials. It is unclear if the results pertain to patients with cancer and VTE. Data from two randomised trials comparing dabigatran and warfarin for acute VTE were pooled. Primary efficacy outcome was symptomatic recurrent VTE and related death from randomisation to the end of the treatment period. Safety outcomes were major, major and clinically relevant non-major, and any bleeding during the oral-only treatment period. Patients with active cancer (=within 5 years) at baseline or diagnosed during the study were analysed. Compared with 4,772 patients without cancer, recurrent VTE occurred more frequently in 335 patients with cancer at any time (hazard ratio [HR] 3.3; 95 % confidence interval [CI], 2.1–5.3) and more often in 114 with cancer diagnosed during the study compared to 221 with cancer at baseline (HR 2.6; 95 % CI, 1.1–6.2). There was no significant difference in efficacy between dabigatran and warfarin for cancer at baseline (HR 0.75; 95 % CI, 0.20–2.8) or diagnosed during the study (HR 0.63; 95 % CI, 0.20–2.0). Major bleeding (HR 4.1; 95 % CI, 2.2–7.5) and any bleeding (HR 1.5; 95 % CI, 1.2–2.0) were more frequent in patients with cancer than without, but with similar incidence in cancer with dabigatran or warfarin. In conclusion, in cancer patients, dabigatran provided similar clinical benefit as warfarin. VTE recurrence or bleeding were similar in patients on dabigatran or warfarin. The efficacy of dabigatran has not been assessed in comparison with low-molecular-weight heparin.

[1]  G. Lip,et al.  Non-Vitamin K Antagonist Oral Anticoagulants and the Treatment of Venous Thromboembolism in Cancer Patients: A Semi Systematic Review and Meta-Analysis of Safety and Efficacy Outcomes , 2014, PloS one.

[2]  H. Büller,et al.  Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. , 2014, Blood.

[3]  Lara A. Kahale,et al.  Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer. , 2014, The Cochrane database of systematic reviews.

[4]  池田 正孝 ガイドライン解説 Venous thromboembolism prophylaxis and treatment in patients with cancer : American Society of Clinical Oncology clinical practice guideline update , 2014 .

[5]  S. Goldhaber,et al.  Treatment of Acute Venous Thromboembolism With Dabigatran or Warfarin and Pooled Analysis , 2014, Circulation.

[6]  I. Meijerman,et al.  PXR-mediated P-glycoprotein induction by small molecule tyrosine kinase inhibitors. , 2013, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[7]  E. Rahme,et al.  Anticoagulant use in patients with cancer associated venous thromboembolism: a retrospective cohort study. , 2013, Thrombosis research.

[8]  A. Khorana,et al.  International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer , 2013, Journal of thrombosis and haemostasis : JTH.

[9]  F. Dentali,et al.  Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. , 2012, Chest.

[10]  M. Levine,et al.  Warfarin Dose Assessment Every 4 Weeks Versus Every 12 Weeks in Patients With Stable International Normalized Ratios , 2011, Annals of Internal Medicine.

[11]  D Bergqvist,et al.  Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients , 2010, Journal of thrombosis and haemostasis : JTH.

[12]  J. Schellens,et al.  PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line , 2009, Cancer Chemotherapy and Pharmacology.

[13]  S. Goldhaber,et al.  Dabigatran versus warfarin in the treatment of acute venous thromboembolism. , 2009, The New England journal of medicine.

[14]  G. Raskob,et al.  Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[15]  S. Schulman,et al.  Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non‐surgical patients , 2005, Journal of thrombosis and haemostasis : JTH.

[16]  M. Prins,et al.  Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. , 2003, The New England journal of medicine.

[17]  M. Prins,et al.  Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. , 2002, Blood.

[18]  M Gent,et al.  Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  R. Hull,et al.  Antithrombotic therapy for venous thromboembolic disease. , 1989 .

[20]  R. Hull,et al.  Antithrombotic therapy for venous thromboembolic disease. , 1995, Chest.