Thromb Haemost 2017; 117(07): 1317-1325
DOI: 10.1160/TH17-01-0065
Review Article
Schattauer GmbH

NOACs for treatment of venous thromboembolism in clinical practice

Sam Schulman
1   Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, Ontario, Canada
,
Daniel Singer
2   Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
,
Walter Ageno
3   University of Insubria, Varese, Italy
,
Ivan B. Casella
4   University of Sao Paulo, Sao Paulo, Brazil
,
Marc Desch
5   Boehringer Ingelheim, Germany
,
Samuel Z. Goldhaber
6   Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 30. Januar 2017

Accepted after major revision: 05. April 2017

Publikationsdatum:
28. November 2017 (online)

Summary

Randomised controlled trials have provided important information on the efficacy and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) for treatment of venous thromboembolism (VTE), leading to registration and increasing use in clinical practice. Many questions remain to be answered, and observational studies are often more suitable for answering “real-world” questions than randomised controlled trials. Patient satisfaction, quality of life, and adherence and persistence in clinical practice with the drug regimen can only be assessed with an open-label design. Evaluation of risk for long-term sequelae of the disease requires much longer follow-up than is possible in registration trials. Treatment patterns and utilisation of health care resources can be assessed from observations in the clinical practice setting. We will review published as well as currently active observational studies with NOACs in VTE, with or without a comparator anticoagulant. These studies are based on cohorts of different sizes, registries, or administrative health care databases. We will also discuss some limitations in analysis and interpretation of observational studies.

 
  • References

  • 1 Cohen AT, Hamilton M, Mitchell SA. et al. Comparison of the novel oral anticoagulants apixaban, dabigatran, edoxaban, and rivaroxaban in the initial and long-term treatment and prevention of venous thromboembolism: systematic review and network meta-analysis. PLoS One 2015; 10: e0144856.
  • 2 Freedman B, Lip GY. “Unreal world„ or “real world„ data in oral anticoagulant treatment of atrial fibrillation. Thromb Haemost 2016; 116: 587-589.
  • 3 Larsen TB, Skjoth F, Nielsen PB. et al. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. Br Med J 2016; 353: i3189.
  • 4 Graham DJ, Reichman ME, Wernecke M. et al. Cardiovascular, bleeding, and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation. Circulation 2015; 131: 157-164.
  • 5 Carmo J, Moscoso Costa F, Ferreira J. et al. Dabigatran in real-world atrial fibrillation. Meta-analysis of observational comparison studies with vitamin K antagonists. Thromb Haemost 2016; 116: 754-763.
  • 6 Romanelli RJ, Nolting L, Dolginsky M. et al. Dabigatran Versus Warfarin for Atrial Fibrillation in Real-World Clinical Practice: A Systematic Review and Meta-Analysis. Circ Cardiovasc Qual Outcomes 2016; 9: 126-134.
  • 7 Castellucci LA, Shaw J, van der Salm K. et al. Self-reported adherence to anticoagulation and its determinants using the Morisky medication adherence scale. Thromb Res 2015; 136: 727-731.
  • 8 Badreldin H, Nichols H, Rimsans J. et al. Evaluation of anticoagulation selection for acute venous thromboembolism. J Thromb Thrombolysis 2017; 43: 74-78.
  • 9 Paczynska M, Kurnicka K, Lichodziejewska B. et al. Acute pulmonary embolism treatment with rivaroxaban results in a shorter duration of hospitalisation compared to standard therapy: an academic centre experience. Kardiol Pol 2016; 74: 650-656.
  • 10 Sharifi M, Freeman W, Bay C. et al. Low incidence of post-thrombotic syndrome in patients treated with new oral anticoagulants and percutaneous endovenous intervention for lower extremity deep venous thrombosis. Vasc Med 2015; 20: 112-116.
  • 11 Ross JA, Miller M, Hernandez CR. OC-13 – Safe and effective use of direct oral anticoagulants (DOAC) versus conventional anticoagulation for the treatment of cancer-related venous thromboembolism. Thromb Res 2016; 140 (Suppl. 01) S173-S174.
  • 12 Ageno W, Mantovani LG, Haas S. et al. XALIA: rationale and design of a non-interventional study of rivaroxaban compared with standard therapy for initial and long-term anticoagulation in deep vein thrombosis. Thromb J 2014; 12: 16.
  • 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: e12-e21.
  • 14 Beyer-Westendorf J, Gelbricht V, Forster K. et al. Safety of switching from vitamin K antagonists to dabigatran or rivaroxaban in daily care--results from the Dresden NOAC registry. Br J Clin Pharmacol 2014; 78: 908-917.
  • 15 Beyer-Westendorf J, Forster K, Pannach S. et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood 2014; 124: 955-962.
  • 16 Kucher N, Aujesky D, Beer JH. et al. Rivaroxaban for the treatment of venous thromboembolism. The SWIss Venous ThromboEmbolism Registry (SWIVTER). Thromb Haemost 2016; 116: 472-479.
  • 17 Agnelli G, Gitt AK, Bauersachs R. et al. The management of acute venous thromboembolism in clinical practice – study rationale and protocol of the European PREFER in VTE Registry. Thromb J 2015; 13: 41.
  • 18 Guercini F, Mommi V, Camporese G. et al. The management of patients with venous thromboembolism in Italy: insights from the PREFER in VTE registry. Intern Emerg Med 2016; 11: 1095-1102.
  • 19 Sindet-Pedersen C, Pallisgaard JL, Staerk L. et al. Comparative safety and effectiveness of rivaroxaban versus vitamin K antagonists in patients with venous thromboembolism – A Danish nationwide registry-based study. Thromb Haemost 2017 ; Epub ahead of print.
  • 20 Weitz JI, Haas S, Ageno W. et al. Global Anticoagulant Registry in the Field - Venous Thromboembolism (GARFIELD-VTE). Rationale and design. Thromb Haemost 2016; 116: 1172-1179.
  • 21 Cano SJ, Lamping DL, Bamber L. et al. The Anti-Clot Treatment Scale (ACTS) in clinical trials: cross-cultural validation in venous thromboembolism patients. Health Qual Life Outcomes 2012; 10: 120.
  • 22 Ageno W, Casella I, Han CK. et al. RE-COVERY DVT/PE: Rationale and design of a prospective observational study of acute venous thromboembolism with a focus on dabigatran etexilate. Thromb Haemost 2017; 117: 415-421.
  • 23 King G, Nielsen R. Why propensity scores should not be used for matching. 2016 Available from http://gking.harvard.edu/files/gking/files/psnot.pdf Accessed November 6, 2016
  • 24 Landefeld CS, Anderson PA, Goodnough LT. et al. The bleeding severity index: validation and comparison to other methods for classifying bleeding complications of medical therapy. J Clin Epidemiol 1989; 42: 711-718.
  • 25 Limone BL, Hernandez AV, Michalak D. et al. Timing of recurrent venous thromboembolism early after the index event: a meta-analysis of randomized controlled trials. Thromb Res 2013; 132: 420-426.
  • 26 Schulman S, Kearon C, Kakkar AK. et al. Extended use of dabigatran, warfarin or placebo in venous thromboembolism. N Engl J Med 2013; 368: 709-718.
  • 27 Kearon C, Ageno W, Cannegieter SC. et al. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost 2016; 14: 1480-1483.
  • 28 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692-694.
  • 29 Kaatz S, Ahmad D, Spyropoulos AC. et al. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13: 2119-2126.
  • 30 Kahn SR, Partsch H, Vedantham S. et al. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J Thromb Haemost 2009; 7: 879-883.
  • 31 Connolly SJ, Ezekowitz MD, Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
  • 32 Schulman S, Kearon C, Kakkar AK. et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361: 2342-2352.
  • 33 Martinelli I, Lensing AW, Middeldorp S. et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. Blood 2016; 127: 1417-1425.
  • 34 Yavuz B, Ayturk M, Ozkan S. et al. A real world data of dabigatran etexilate: multicenter registry of oral anticoagulants in nonvalvular atrial fibrillation. J Thromb Thrombolysis 2016; 42: 399-404.
  • 35 Staerk L, Gislason GH, Lip GY. et al. Risk of gastrointestinal adverse effects of dabigatran compared with warfarin among patients with atrial fibrillation: a nationwide cohort study. Europace 2015; 17: 1215-1222.
  • 36 O’Dea D, Whetteckey J, Ting N. A prospective, randomized, open-label study to evaluate two management strategies for gastrointestinal symptoms in patients newly on treatment with dabigatran. Cardiol Ther 2016; 5: 187-201.
  • 37 De Crem N, Peerlinck K, Vanassche T. et al. Abnormal uterine bleeding in VTE patients treated with rivaroxaban compared to vitamin K antagonists. Thromb Res 2015; 136: 749-753.
  • 38 Beyer-Westendorf J, Michalski F, Tittl L. et al. Management and outcomes of vaginal bleeding and heavy menstrual bleeding in women of reproductive age on direct oral anti-factor Xa inhibitor therapy: a case series. Lancet Haematol 2016; 3: e480-e488.
  • 39 Beyer-Westendorf J, Michalski F, Tittl L. et al. Vaginal bleeding and heavy menstrual bleeding during direct oral anti-Xa inhibitor therapy. Thromb Haemost 2016; 115: 1234-1236.
  • 40 Lopes LC, Spencer FA, Neumann I. et al. Bleeding risk in atrial fibrillation patients taking vitamin k antagonists: systematic review and meta-analysis. Clin Pharmacol Ther 2013; 94: 367-375.