CC BY-NC-ND 4.0 · Thromb Haemost 2020; 120(01): 014-026
DOI: 10.1055/s-0039-3400302
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Broadening the Categories of Patients Eligible for Extended Venous Thromboembolism Treatment

Marc Schindewolf
1   Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
,
Jeffrey Ian Weitz
2   Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada
› Institutsangaben
Funding This study was funded by Bayer AG.
Weitere Informationen

Publikationsverlauf

27. Juni 2019

26. September 2019

Publikationsdatum:
13. Dezember 2019 (online)

Abstract

Traditionally, venous thromboembolism (VTE) resulting from major transient risk factors (e.g., surgery or trauma) or a major persistent risk factor such as cancer, has been defined as being provoked, whereas unprovoked VTE encompasses events without an identifiable cause. These categorizations influence anticoagulant treatment duration; unlike VTE provoked by major transient risk factors, extended anticoagulation beyond 3 months is advised for patients with cancer or unprovoked VTE due to risk persistence after treatment cessation. However, some patients with VTE provoked by minor transient or minor persistent risk factors may also be candidates for extended anticoagulation therapy due to the continuing risk of recurrence. In patients who require extended therapy, vitamin K antagonists (VKAs) are effective but are associated with an increased risk of bleeding and various treatment burdens (e.g., anticoagulation monitoring and dose adjustment). Evaluations of extended VTE treatment with the less-burdensome direct oral anticoagulants such as apixaban, dabigatran, edoxaban, and rivaroxaban show that they are at least as safe and effective as VKAs in a broad range of patients. In addition, apixaban and rivaroxaban offer more than one dosing option, allowing tailoring of treatment to the patient's specific risk factor profile. Analysis of more granular definitions for risk factor groupings has also yielded vital information on the most appropriate strategies for the treatment of patients with specific risk factors, highlighting that extended anticoagulation treatment may benefit those with minor transient and persistent environmental and nonenvironmental risk factors who commonly receive shorter-duration therapy.

 
  • References

  • 1 Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015; 12 (08) 464-474
  • 2 Cohen AT, Agnelli G, Anderson FA. , et al; VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost 2007; 98 (04) 756-764
  • 3 Konstantinides SV, Torbicki A, Agnelli G. , et al; Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35 (43) 3033-3069
  • 4 Kearon C, Akl EA. Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood 2014; 123 (12) 1794-1801
  • 5 Kearon C, Ageno W, Cannegieter SC, Cosmi B, Geersing GJ, Kyrle PA. ; Subcommittees on Control of Anticoagulation, and Predictive and Diagnostic Variables in Thrombotic Disease. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost 2016; 14 (07) 1480-1483
  • 6 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
  • 7 Mazzolai L, Aboyans V, Ageno W. , et al. Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European Society of Cardiology working groups of aorta and peripheral vascular diseases and pulmonary circulation and right ventricular function. Eur Heart J 2018; 39 (47) 4208-4218
  • 8 Boutitie F, Pinede L, Schulman S. , et al. Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants' data from seven trials. BMJ 2011; 342: d3036
  • 9 Prins MH, Lensing AWA, Prandoni P. , et al. Risk of recurrent venous thromboembolism according to baseline risk factor profiles. Blood Adv 2018; 2 (07) 788-796
  • 10 Heit JA, Mohr DN, Silverstein MD, Petterson TM, O'Fallon WM, Melton III LJ. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 2000; 160 (06) 761-768
  • 11 Iorio A, Kearon C, Filippucci E. , et al. Risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic review. Arch Intern Med 2010; 170 (19) 1710-1716
  • 12 Hutten BA, Prins MH. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev 2006; (01) CD001367
  • 13 Middeldorp S, Prins MH, Hutten BA. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev 2014; (08) CD001367
  • 14 Ridker PM, Goldhaber SZ, Danielson E. , et al; PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348 (15) 1425-1434
  • 15 Kearon C, Ginsberg JS, Kovacs MJ. , et al; Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349 (07) 631-639
  • 16 Amin A, Marrs JC. Direct oral anticoagulants for the management of thromboembolic disorders: the importance of adherence and persistence in achieving beneficial outcomes. Clin Appl Thromb Hemost 2016; 22 (07) 605-616
  • 17 van der Hulle T, den Exter PL, Kooiman J, van der Hoeven JJ, Huisman MV, Klok FA. Meta-analysis of the efficacy and safety of new oral anticoagulants in patients with cancer-associated acute venous thromboembolism. J Thromb Haemost 2014; 12 (07) 1116-1120
  • 18 Prins MH, Lensing AWA, 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 (01) e37-e46
  • 19 van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 2014; 124 (12) 1968-1975
  • 20 Bauersachs R, Gitt AK, Mismetti P. , et al. Readmittance to hospital within 6 months after a venous thromboembolism event: PREFER in VTE registry. Value Health 2014; 17 (07) A472-A473
  • 21 Di Nisio M, Vedovati MC, Riera-Mestre A. , et al. Treatment of venous thromboembolism with rivaroxaban in relation to body weight. A sub-analysis of the EINSTEIN DVT/PE studies. Thromb Haemost 2016; 116 (04) 739-746
  • 22 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
  • 23 Goldhaber SZ, Eriksson H, Kakkar A. , et al. Efficacy of dabigatran versus warfarin in patients with acute venous thromboembolism in the presence of thrombophilia: findings from RE-COVER®, RE-COVER™ II, and RE-MEDY™. Vasc Med 2016; 21 (06) 506-514
  • 24 Schulman S, Goldhaber SZ, Kearon C. , et al. Treatment with dabigatran or warfarin in patients with venous thromboembolism and cancer. Thromb Haemost 2015; 114 (01) 150-157
  • 25 Schulman S, Kearon C, Kakkar AK. , et al; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013; 368 (08) 709-718
  • 26 Agnelli G, Buller HR, Cohen A. , et al; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013; 368 (08) 699-708
  • 27 Bauersachs R, Berkowitz SD, Brenner B. , et al; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363 (26) 2499-2510
  • 28 Weitz JI, Lensing AWA, Prins MH. , et al; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med 2017; 376 (13) 1211-1222
  • 29 Raskob G, Ageno W, Cohen AT. , et al. Extended duration of anticoagulation with edoxaban in patients with venous thromboembolism: a post-hoc analysis of the Hokusai-VTE study. Lancet Haematol 2016; 3 (05) e228-e236
  • 30 Bristol-Myers Squibb. Pfizer. Eliquis® (apixaban) Summary of Product Characteristics. 2019 . Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf . Accessed August 29, 2019
  • 31 Simes J, Becattini C, Agnelli G. , et al; INSPIRE Study Investigators (International Collaboration of Aspirin Trials for Recurrent Venous Thromboembolism). Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration. Circulation 2014; 130 (13) 1062-1071
  • 32 Bayer AG. Xarelto® (rivaroxaban) Summary of Product Characteristics. 2019 . Available at: https://www.ema.europa.eu/documents/product-information/xarelto-epar-product-information_en.pdf . Accessed August 29, 2019
  • 33 Janssen Pharmaceuticals Inc. Xarelto® (rivaroxaban) Prescribing Information. 2019 . Available at: http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/XARELTO-pi.pdf . Accessed August 29, 2019
  • 34 Prandoni P, Lensing AWA, Prins MH. , et al. Benefits and risks of extended treatment of venous thromboembolism with rivaroxaban or with aspirin. Thromb Res 2018; 168: 121-129
  • 35 Büller HR, Décousus H, Grosso MA. , et al; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369 (15) 1406-1415
  • 36 Peñaloza-Martínez E, Demelo-Rodríguez P, Proietti M. , et al. Update on extended treatment for venous thromboembolism. Ann Med 2018; 50 (08) 666-674
  • 37 Prandoni P, Noventa F, Ghirarduzzi A. , et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007; 92 (02) 199-205
  • 38 Donadini MP, Ageno W, Antonucci E. , et al. Prognostic significance of residual venous obstruction in patients with treated unprovoked deep vein thrombosis: a patient-level meta-analysis. Thromb Haemost 2014; 111 (01) 172-179
  • 39 Douketis J, Tosetto A, Marcucci M. , et al. Risk of recurrence after venous thromboembolism in men and women: patient level meta-analysis. BMJ 2011; 342: d813
  • 40 Eichinger S, Hron G, Bialonczyk C. , et al. Overweight, obesity, and the risk of recurrent venous thromboembolism. Arch Intern Med 2008; 168 (15) 1678-1683
  • 41 Novacek G, Weltermann A, Sobala A. , et al. Inflammatory bowel disease is a risk factor for recurrent venous thromboembolism. Gastroenterology 2010; 139 (03) 779-787
  • 42 Rattazzi M, Villalta S, De Lucchi L. , et al. Chronic kidney disease is associated with increased risk of venous thromboembolism recurrence. Thromb Res 2017; 160: 32-37
  • 43 Marchiori A, Mosena L, Prins MH, Prandoni P. The risk of recurrent venous thromboembolism among heterozygous carriers of factor V Leiden or prothrombin G20210A mutation. A systematic review of prospective studies. Haematologica 2007; 92 (08) 1107-1114
  • 44 De Stefano V, Simioni P, Rossi E. , et al. The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. Haematologica 2006; 91 (05) 695-698
  • 45 Zöller B, Ohlsson H, Sundquist J, Sundquist K. Family history of venous thromboembolism (VTE) and risk of recurrent hospitalization for VTE: a nationwide family study in Sweden. J Thromb Haemost 2014; 12 (03) 306-312
  • 46 Hron G, Eichinger S, Weltermann A. , et al. Family history for venous thromboembolism and the risk for recurrence. Am J Med 2006; 119 (01) 50-53
  • 47 Streiff MB. Predicting the risk of recurrent venous thromboembolism (VTE). J Thromb Thrombolysis 2015; 39 (03) 353-366
  • 48 Carrier M, Rodger MA, Wells PS, Righini M, LE Gal G. Residual vein obstruction to predict the risk of recurrent venous thromboembolism in patients with deep vein thrombosis: a systematic review and meta-analysis. J Thromb Haemost 2011; 9 (06) 1119-1125
  • 49 Vasanthamohan L, Boonyawat K, Chai-Adisaksopha C, Crowther M. Reduced-dose direct oral anticoagulants in the extended treatment of venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 2018; 16 (07) 1288-1295
  • 50 Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14 (06) 1308-1313
  • 51 Bristol-Myers Squibb Company. Pfizer Inc. Eliquis® (apixaban) Prescribing information. 2019 . Available at: http://packageinserts.bms.com/pi/pi_eliquis.pdf . Accessed August 29, 2019
  • 52 Daiichi Sankyo Europe Gmb H. Lixiana® (edoxaban) Summary of Product Characteristics. 2019 . Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002629/WC500189045.pdf . Accessed August 29, 2019
  • 53 Daiichi Sankyo Inc. Savaysa® (edoxaban) Prescribing information. 2017 . Available at: http://dsi.com/prescribing-information-portlet/getPIContent?productName=Savaysa&inline=true . Accessed August 29, 2018
  • 54 Boehringer Ingelheim International GmbH. Pradaxa® (dabigatran etexilate) Summary of Product Characteristics. 2019 . Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf . Accessed August 29, 2019
  • 55 Boehringer Ingelheim Pharmaceuticals Inc. Pradaxa® (dabigatran etexilate) prescribing information. 2018 . Available at: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf . Accessed August 29, 2019
  • 56 Netley J, Howard K, Wilson W. Effects of body mass index on the safety and effectiveness of direct oral anticoagulants: a retrospective review. J Thromb Thrombolysis 2019; 48 (03) 359-365
  • 57 Prandoni P, Villalta S, Tormene D, Spiezia L, Pesavento R. Immobilization resulting from chronic medical diseases: a new risk factor for recurrent venous thromboembolism in anticoagulated patients. J Thromb Haemost 2007; 5 (08) 1786-1787
  • 58 Nemeth B, Timp JF, van Hylckama Vlieg A, Rosendaal FR, Cannegieter SC. High risk of recurrent venous thrombosis in patients with lower-leg cast immobilization. J Thromb Haemost 2018; 16 (11) 2218-2222
  • 59 Pabinger I, Grafenhofer H, Kyrle PA. , et al. Temporary increase in the risk for recurrence during pregnancy in women with a history of venous thromboembolism. Blood 2002; 100 (03) 1060-1062
  • 60 De Stefano V, Martinelli I, Rossi E. , et al. The risk of recurrent venous thromboembolism in pregnancy and puerperium without antithrombotic prophylaxis. Br J Haematol 2006; 135 (03) 386-391
  • 61 Olié V, Plu-Bureau G, Conard J, Horellou MH, Canonico M, Scarabin PY. Hormone therapy and recurrence of venous thromboembolism among postmenopausal women. Menopause 2011; 18 (05) 488-493