Semin Thromb Hemost 2018; 44(03): 261-266
DOI: 10.1055/s-0038-1637750
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Direct Oral Anticoagulants and the Paradigm Shift in the Management of Venous Thromboembolism

Hui Yin Lim
1   Department of Haematology, Northern Health, Epping, Victoria, Australia
2   Australian Centre for Blood Diseases, Melbourne, Victoria, Australia
3   The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
,
Harshal Nandurkar
2   Australian Centre for Blood Diseases, Melbourne, Victoria, Australia
,
Prahlad Ho
1   Department of Haematology, Northern Health, Epping, Victoria, Australia
2   Australian Centre for Blood Diseases, Melbourne, Victoria, Australia
3   The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
› Author Affiliations
Further Information

Publication History

Publication Date:
20 March 2018 (online)

Abstract

The advent of direct oral anticoagulants (DOACs) has revolutionized anticoagulation management in both stroke prevention and venous thromboembolism (VTE) treatment/prevention. Clinical trials and secondary real-world data have shown that DOACs have similar efficacy and, in some cases, improved bleeding safety profiles compared with vitamin K antagonists. Together with benefits of patient convenience, this has shifted the risk–benefit ratio toward long-term anticoagulation. However, current VTE risk assessment models are based on vitamin K antagonists and do not take into account the new paradigm of DOACs. Therefore, challenges to the thrombosis community remain to determine patients who would benefit from long-term anticoagulation in the DOAC era. Here, the authors review the current literature on risks and benefits of DOACs and their potential role in long-term VTE thromboprophylaxis as well as in current risk assessment models. The increasing use of DOACs, led by their convenience of use and generally lower bleeding rates, calls for a reevaluation of the current models as the benefits of long-term anticoagulation may begin to outweigh risks and inconvenience associated with their predecessors.

 
  • References

  • 1 Agnelli G, Buller HR, Cohen A. , et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (09) 799-808
  • 2 Connolly SJ, Ezekowitz MD, Yusuf S. , et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
  • 3 Granger CB, Alexander JH, McMurray JJV. , et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
  • 4 Patel MR, Mahaffey KW, Garg J. , et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
  • 5 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
  • 6 Schulman S, Kearon C, Kakkar AK. , et al; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361 (24) 2342-2352
  • 7 Tran H, Joseph J, Young L. , et al; Australasian Society of Thrombosis and Haemostasis. New oral anticoagulants: a practical guide on prescription, laboratory testing and peri-procedural/bleeding management. Intern Med J 2014; 44 (06) 525-536
  • 8 Pokorney SD, Simon DN, Thomas L. , et al; Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Investigators. Patients' time in therapeutic range on warfarin among US patients with atrial fibrillation: results from ORBIT-AF registry. Am Heart J 2015; 170 (01) 141-148 , 148.e1
  • 9 Barnes GD, Lucas E, Alexander GC, Goldberger ZD. National trends in ambulatory oral anticoagulant use. Am J Med 2015; 128 (12) 1300-5.e2
  • 10 Ho P, Brooy BL, Hayes L, Lim WK. Direct oral anticoagulants in frail older adults: a geriatric perspective. Semin Thromb Hemost 2015; 41 (04) 389-394
  • 11 Lip GY, Pan X, Kamble S. , et al. Major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin: a “real-world” observational study in the United States. Int J Clin Pract 2016; 70 (09) 752-763
  • 12 Yao X, Abraham NS, Sangaralingham LR. , et al. Effectiveness and safety of Dabigatran, Rivaroxaban, and Apixaban versus Warfarin in nonvalvular atrial fibrillation. J Am Heart Assoc 2016; 5 (06) e003725
  • 13 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 (01) e12-e21
  • 14 Raskob GE, van Es N, Verhamme P. , et al; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 2018; 378 (07) 615-624
  • 15 Cohen H, Hunt BJ, Efthymiou M. , et al; RAPS trial investigators. Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomised, controlled, open-label, phase 2/3, non-inferiority trial. Lancet Haematol 2016; 3 (09) e426-e436
  • 16 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
  • 17 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
  • 18 Winter MP, Schernthaner GH, Lang IM. Chronic complications of venous thromboembolism. J Thromb Haemost 2017; 15 (08) 1531-1540
  • 19 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
  • 20 Lim HY, Chua CC, Tacey M. , et al. Venous thromboembolism management in Northeast Melbourne: how does it compare to international guidelines and data?. Intern Med J 2017; 47 (09) 1034-1042
  • 21 Ho P, Lim HY, Chua CC. , et al. Retrospective review on isolated distal deep vein thrombosis (IDDVT) - a benign entity or not?. Thromb Res 2016; 142: 11-16
  • 22 Chua CC, Lim HY, Tacey M, Nandurkar H, Ho P. Retrospective evaluation of venous thromboembolism: are all transient provoking events the same?. Eur J Haematol 2017; 99 (01) 18-26
  • 23 De Stefano V, Martinelli I, Mannucci PM. , et al. The risk of recurrent deep venous thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med 1999; 341 (11) 801-806
  • 24 Segal JB, Brotman DJ, Necochea AJ. , et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA 2009; 301 (23) 2472-2485
  • 25 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
  • 26 Favaloro EJ, Mohammed S, Pati N, Ho MY, McDonald D. A clinical audit of congenital thrombophilia investigation in tertiary practice. Pathology 2011; 43 (03) 266-272
  • 27 Palareti G, Cosmi B, Legnani C. , et al; PROLONG Investigators. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 2006; 355 (17) 1780-1789
  • 28 Cosmi B, Legnani C, Tosetto A. , et al. Use of D-dimer testing to determine duration of anticoagulation, risk of cardiovascular events and occult cancer after a first episode of idiopathic venous thromboembolism: the extended follow-up of the PROLONG study. J Thromb Thrombolysis 2009; 28 (04) 381-388
  • 29 Cosmi B, Legnani C, Tosetto A. , et al; PROLONG Investigators (on behalf of Italian Federation of Anticoagulation Clinics). Usefulness of repeated D-dimer testing after stopping anticoagulation for a first episode of unprovoked venous thromboembolism: the PROLONG II prospective study. Blood 2010; 115 (03) 481-488
  • 30 Eichinger S, Heinze G, Jandeck LM, Kyrle PA. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation 2010; 121 (14) 1630-1636
  • 31 Tosetto A, Iorio A, Marcucci M. , et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost 2012; 10 (06) 1019-1025
  • 32 Eichinger S, Hron G, Kollars M, Kyrle PA. Prediction of recurrent venous thromboembolism by endogenous thrombin potential and D-dimer. Clin Chem 2008; 54 (12) 2042-2048
  • 33 Becattini C, Agnelli G, Schenone A. , et al; WARFASA Investigators. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012; 366 (21) 1959-1967
  • 34 Nielsen PB, Skjøth F, Søgaard M, Kjældgaard JN, Lip GYH, Larsen TB. Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ 2017; 356: j510
  • 35 Hass B, Pooley J, Harrington AE, Clemens A, Feuring M. Treatment of venous thromboembolism - effects of different therapeutic strategies on bleeding and recurrence rates and considerations for future anticoagulant management. Thromb J 2012; 10 (01) 24
  • 36 Lijfering WM, Middeldorp S, Veeger NJ. , et al. Risk of recurrent venous thrombosis in homozygous carriers and double heterozygous carriers of factor V Leiden and prothrombin G20210A. Circulation 2010; 121 (15) 1706-1712
  • 37 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
  • 38 Pengo V, Ruffatti A, Legnani C. , et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost 2010; 8 (02) 237-242