Meta‐analysis of the efficacy and safety of new oral anticoagulants in patients with cancer‐associated acute venous thromboembolism: comment

SummaryIntroduction Treatment of acute venous thromboembolism (VTE) in cancer patients is challenging, owing to a high risk of recurrent VTE and bleeding complications. The anticoagulants of choice are low molecular weight heparins (LMWHs), because of a proven higher efficacy than vitamin K antagonists (VKAs) and a similar bleeding profile. The recently introduced new oral anticoagulants (NOACs) have the potential to be alternative options for these patients, as these drugs share practical advantages with LMWH, are administered orally, and had similar efficacy to VKAs but a lower bleeding risk in phase 3 studies in the general VTE population. Methods A systematic literature search was performed to identify phase 3 trials investigating NOACs for the treatment of VTE. The efficacy outcome was recurrent VTE, and the safety outcome was major and clinically relevant non-major bleeding. Pooled incidence rates and risk ratios (RRs) were calculated for cancer patients and non-cancer patients separately. Results and discussion Five studies were included, with 19 060 patients, of whom 973 (5.1%) had active cancer. The pooled incidence rates of recurrent VTE were 4.1% (95% confidence interval [CI] 2.6–6.0) in cancer patients treated with NOACs, and 6.1% (95% CI 4.1–8.5) in patients treated with VKAs (RR 0.66, 95% CI 0.38–1.2). The pooled incidence rates of major or non-major clinically relevant bleeding were 15% (95% CI 12–18) in cancer patients treated with NOACs, and 16% (95% CI 9.9–22) in patients treated with VKAs (RR 0.94, 95% CI 0.70–1.3). These results form a solid basis for the initiation of a head-to-head comparison of NOACs with LMWH in cancer patients.

[1]  Gary H Lyman,et al.  Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update 2014. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  F. Klok,et al.  Meta‐analysis of the efficacy and safety of new oral anticoagulants in patients with cancer‐associated acute venous thromboembolism: reply , 2014, Journal of thrombosis and haemostasis : JTH.

[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]  Huisman,et al.  Meta‐analysis of the efficacy and safety of new oral anticoagulants in patients with cancer‐associated acute venous thromboembolism , 2014, Journal of thrombosis and haemostasis : JTH.

[5]  O. Dekkers,et al.  Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta‐analysis , 2014, Journal of thrombosis and haemostasis : JTH.

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

[7]  S. Goldhaber,et al.  Influence Of Concomitant NSAID Or ASA On The Efficacy and Safety Of Dabigatran Versus Warfarin For The Treatment Of Acute Venous Thromboembolism: A Pooled Analysis From RE-Cover and RE-Cover II , 2013 .

[8]  G. Raskob,et al.  Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. , 2013, The New England journal of medicine.

[9]  Giancarlo Agnelli,et al.  Oral apixaban for the treatment of acute venous thromboembolism. , 2013, The New England journal of medicine.

[10]  H. Nar,et al.  A specific antidote for dabigatran: functional and structural characterization. , 2013, Blood.

[11]  P. Conley,et al.  A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa , 2013, Nature Medicine.

[12]  F. García-Bragado Dalmau [Oral Rivaroxaban for the treatment of symptomatic pulmonary embolism]. , 2013, Revista clinica espanola.

[13]  G. Raskob,et al.  Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. , 2012, The New England journal of medicine.

[14]  G. Guyatt,et al.  Introduction to the ninth edition: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. , 2012, Chest.

[15]  Paolo Prandoni,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.

[16]  J. Sterne,et al.  The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials , 2011, BMJ : British Medical Journal.

[17]  G. Agnelli,et al.  Management of venous thromboembolism in patients with cancer , 2011, Journal of thrombosis and haemostasis : JTH.

[18]  R. Gans,et al.  Oral rivaroxaban for symptomatic venous thromboembolism. , 2011, The New England journal of medicine.

[19]  Bruce L Davidson,et al.  Oral rivaroxaban for symptomatic venous thromboembolism. , 2010, The New England journal of medicine.

[20]  K. Peter,et al.  New oral anticoagulant drugs in cardiovascular disease , 2010, Thrombosis and Haemostasis.

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

[22]  E. Akl,et al.  Anticoagulation for the long term treatment of venous thromboembolism in patients with cancer. , 2008, The Cochrane database of systematic reviews.

[23]  A. Khorana,et al.  Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy , 2007, Journal of thrombosis and haemostasis : JTH.

[24]  H. Chew,et al.  Incidence of venous thromboembolism and its effect on survival among patients with common cancers. , 2006, Archives of internal medicine.

[25]  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.

[26]  Paolo Prandoni,et al.  Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. , 2002, Blood.

[27]  G. Lip,et al.  The hypercoagulable state of malignancy: pathogenesis and current debate. , 2002, Neoplasia.

[28]  Yves Gruel,et al.  Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. , 2002, Archives of internal medicine.

[29]  E. Chu,et al.  An adverse interaction between warfarin and capecitabine: a case report and review of the literature. , 2001, Clinical colorectal cancer.

[30]  J. Olsen,et al.  Prognosis of cancers associated with venous thromboembolism. , 2000, The New England journal of medicine.