The efficacy and safety of new oral anticoagulants for cancer-associated venous thromboembolism: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

CHEN Kuangrong ¹ , GUO Qiang ² ,  GONG Shu ³

1. Department of Oncology, The First People’s Hospital of Ziyang, Ziyang, 641300, P.R.China;
2. Department of Vascular Surgery, West China Hospital, Chengdu, 610041, P.R.China;
3. Department of Pancreatic Surgery, West China Hospital, Chengdu, 610041, P.R.China;

Corresponding author：

GONG Shu, Email: gdy-29@163.com

Keywords：

New oral anticoagulants; Cancer; Venous thromboembolism; Systematic review; Meta-analysis

DOI：

10.7507/1672-2531.201806039

Video：

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ObjectivesTo systematically review the efficacy and safety of new oral anticoagulants (NOACs) for cancer-associated venous thromboembolism.MethodsStudies about the efficacy and safety of NOACs versus low molecular weight heparins (LMWHs) or vitamin K antagonists (VKAs) for cancer-associated venous thromboembolism were collected by searching PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and CBM databases from inception to August, 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was then performed by RevMan 5.3 software.ResultsA total of 8 studies involving 2 448 patients were included. The results of meta-analysis showed that: there was no significant difference in the recurrent VTE rate (OR=0.74, 95%CI 0.49 to 1.11, P=0.15) or bleeding rate (OR=0.80, 95%CI 0.57 to 1.13, P=0.21) between NOACs group and VKAs group. The major bleeding rate was significantly higher in the VKAs group than in the NOACs group (OR=0.47, 95%CI 0.27 to 0.84, P=0.01). The incidences of recurrent VTE (OR=0.84, 95%CI 0.16 to 4.14, P=0.83), bleeding (OR=0.46, 95%CI 0.18 to 1.20, P=0.11), major bleeding (OR=0.45, 95%CI 0.12 to 1.60, P=0.21) were similar between NOACs group and LMWHs group.ConclusionsThe current evidence indicates that for cancer patients with VTE, NOACs are superior to warfarin and comparable to LMWHs. Due to limited quantity and quality of the included studies, more high quality studies are required to verify the above conclusion.

Citation： CHEN Kuangrong, GUO Qiang, GONG Shu. The efficacy and safety of new oral anticoagulants for cancer-associated venous thromboembolism: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2018, 18(6): 580-586. doi: 10.7507/1672-2531.201806039 Copy

1.	Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med, 2012, 9(7): e1001275.
2.	Sorensen HT, Mellemkjaer L, Olsen JH, et al. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000, 343(28): 1846-1850.
3.	Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med, 2009, 361(24): 2342-2352.
4.	Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med, 2010, 363: 2499-2510.
5.	Buller HR, Prins MH, Lensin AW, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med, 2012, 366(14): 1287-1297.
6.	Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med, 2013, 369(9): 799-808.
7.	van der Hulle T, Kooiman J, den Exter PL, 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. J Thromb Haemost, 2014, 12(3): 320-328.
8.	Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline. Chest, 2016, 149(2): 315-352.
9.	Lee AY, Levine MN, Baker RI, et al. Low molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349(2): 146-53.
10.	Zeng X, Zhang Y, Kwong JS, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med, 2015, 8(1): 2-10.
11.	Schulman S, Eriksson H, Goldhaber SZ, et al. Influence of active cancer 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. Blood, 2013, 122: 582.
12.	Buller HR, Decousus H, Grosso MA, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med, 2013, 369(15): 1406-1415.
13.	Prins MH, Lensing AW, Brighton TA, et al. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. Lancet Haematol, 2014, 1(1): 37-46.
14.	Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thromb Haemost, 2015, 13(12): 2187-2191.
15.	Ageno W, Mantovani LG, Haas S, et al. Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Lancet Haematol, 2016, 3(1): 12-21.
16.	Gaertner S, Cordeanu EM, Nouri S, et al. Rivaroxaban versus standard anticoagulation for symptomatic venous thromboembolism (REMOTEV observational study): Analysis of 6-month outcomes. Int J Cardiol, 2017, 226: 103-109.
17.	Alzghari SK, Seago SE, Garza JE, et al. Retrospective comparison of low molecular weight heparin vs. warfarin vs. oral Xa inhibitors for the prevention of recurrent venous thromboembolism in oncology patients: The Re-CLOT study. J Oncol Pharm Pract, 2017, 1: 1078155217718382.
18.	Xavier FD, Hoff PMG, Braghiroli MI, et al. Rivaroxaban: An Affordable and Effective Alternative in Cancer-Related Thrombosis? J Glob Oncol, 2016, 3(1): 15-22.
19.	Timp JF, Braekkan SK, Versteeg HH, et al. Epidemiology of cancer-associated venous thrombosis. Blood, 2013, 122: 1712-1723.
20.	Ahrens I, Lip GY, Peter K. New oral anticoagulant drugs in cardiovascular disease. Thromb Haemost 2010, 104(1): 49-60.
21.	Copur MS, Ledakis P, Bolton M, et al. An adverse interaction between warfarin and capecitabine: a case report and review of the literature. Clin Colorectal Cancer, 2001, 1(3): 182-184.
22.	Lu G, DeGuzman FR, Hollenbach SJ, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med, 2013, 19(4): 446-451.

1. Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med, 2012, 9(7): e1001275.
2. Sorensen HT, Mellemkjaer L, Olsen JH, et al. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000, 343(28): 1846-1850.
3. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med, 2009, 361(24): 2342-2352.
4. Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med, 2010, 363: 2499-2510.
5. Buller HR, Prins MH, Lensin AW, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med, 2012, 366(14): 1287-1297.
6. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med, 2013, 369(9): 799-808.
7. van der Hulle T, Kooiman J, den Exter PL, 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. J Thromb Haemost, 2014, 12(3): 320-328.
8. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline. Chest, 2016, 149(2): 315-352.
9. Lee AY, Levine MN, Baker RI, et al. Low molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349(2): 146-53.
10. Zeng X, Zhang Y, Kwong JS, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med, 2015, 8(1): 2-10.
11. Schulman S, Eriksson H, Goldhaber SZ, et al. Influence of active cancer 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. Blood, 2013, 122: 582.
12. Buller HR, Decousus H, Grosso MA, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med, 2013, 369(15): 1406-1415.
13. Prins MH, Lensing AW, Brighton TA, et al. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. Lancet Haematol, 2014, 1(1): 37-46.
14. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thromb Haemost, 2015, 13(12): 2187-2191.
15. Ageno W, Mantovani LG, Haas S, et al. Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Lancet Haematol, 2016, 3(1): 12-21.
16. Gaertner S, Cordeanu EM, Nouri S, et al. Rivaroxaban versus standard anticoagulation for symptomatic venous thromboembolism (REMOTEV observational study): Analysis of 6-month outcomes. Int J Cardiol, 2017, 226: 103-109.
17. Alzghari SK, Seago SE, Garza JE, et al. Retrospective comparison of low molecular weight heparin vs. warfarin vs. oral Xa inhibitors for the prevention of recurrent venous thromboembolism in oncology patients: The Re-CLOT study. J Oncol Pharm Pract, 2017, 1: 1078155217718382.
18. Xavier FD, Hoff PMG, Braghiroli MI, et al. Rivaroxaban: An Affordable and Effective Alternative in Cancer-Related Thrombosis? J Glob Oncol, 2016, 3(1): 15-22.
19. Timp JF, Braekkan SK, Versteeg HH, et al. Epidemiology of cancer-associated venous thrombosis. Blood, 2013, 122: 1712-1723.
20. Ahrens I, Lip GY, Peter K. New oral anticoagulant drugs in cardiovascular disease. Thromb Haemost 2010, 104(1): 49-60.
21. Copur MS, Ledakis P, Bolton M, et al. An adverse interaction between warfarin and capecitabine: a case report and review of the literature. Clin Colorectal Cancer, 2001, 1(3): 182-184.
22. Lu G, DeGuzman FR, Hollenbach SJ, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med, 2013, 19(4): 446-451.

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The efficacy and safety of new oral anticoagulants for cancer-associated venous thromboembolism: a meta-analysis

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