Thromb Haemost 2015; 113(06): 1193-1202
DOI: 10.1160/TH14-12-1036
Theme Issue Article
Schattauer GmbH

Acute phase treatment of VTE: Anticoagulation, including non-vitamin K antagonist oral anticoagulants

Christopher M. Hillis
1   Department of Medicine, McMaster University, Hamilton, Canada
2   Department of Oncology, McMaster University, Hamilton, Canada
,
Mark A. Crowther
1   Department of Medicine, McMaster University, Hamilton, Canada
3   Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 14. Dezember 2014

Accepted after major revision: 28. März 2015

Publikationsdatum:
18. November 2017 (online)

Summary

The acute phase of venous thromboembolism (VTE) treatment focuses on the prompt and safe initiation of full-dose anticoagulation to decrease morbidity and mortality. Immediate management consists of resuscitation, supportive care, and thrombolysis for patients with haemodynamically significant pulmonary embolism (PE) or limb-threatening deep-vein thrombosis (DVT). Patients with contraindications to anticoagulants are considered for vena cava filters. Disposition for the acute treatment of VTE is then considered based on published risk scores and the patient's social status, as the first seven days carries the highest risk for VTE recurrence, extension and bleeding due to anticoagulation. Next, a review of: immediate and long-term bleeding risk, comorbidities (i. e. active cancer, renal failure, obesity, thrombophilia), medications, patient preference, VTE location and potential for pregnancy should be undertaken. This will help determine the most suitable anticoagulant for immediate treatment. The non-vitamin K antagonist oral anticoagulants (NOACs), including the factor Xa inhibitors apixaban, edoxaban and rivaroxaban as well as the directthrombin inhibitor dabigatran, are increasing the convenience of and options available for VTE treatment. Current options for immediate treatment include low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), fondaparinux, apixaban, or rivaroxaban. LMWH or UFH may be continued as monotherapy or transitioned to treatment with a VKA, dabigatran or edoxaban. This review describes the upfront treatment of VTE and the evolving role of NOACs in the contemporary management of VTE.

 
  • References

  • 1 McRae SJ, Ginsberg JS. Initial treatment of venous thromboembolism. Circulation 2004; 110 (09) (Suppl. 01) I3-I9.
  • 2 Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial Lancet 1960; 01: 1309-1312.
  • 3 Tagalakis V. et al. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med 2013; 126 832 e13-e21.
  • 4 Heit JA. et al. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based, cohort study. Arch Intern Med 1999; 159: 445-453.
  • 5 White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107 (23) (Suppl. 01) I4-I8.
  • 6 Bates SM. et al. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (Suppl. 02) e351S-e418S.
  • 7 Blondon M. et al. Usefulness of Preemptive Anticoagulation in Patients With Suspected Pulmonary EmbolismPreemptive Anticoagulation for Pulmonary EmbolismA Decision Analysis. Chest 2012; 142: 697-703.
  • 8 Kearon C. et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis: ACCP evidence-based clinical practice guidelines. Chest 2012; 141 (Suppl. 02) e419S-e94S.
  • 9 Wells PS. et al. Treatment of venous thromboembolism. J Am Med Assoc 2014; 311: 717-728.
  • 10 Kahn SR. et al. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet 2014; 383: 880-888.
  • 11 Hull RD, Gersh MH. The current landscape of treatment options for venous thromboembolism: a focus on novel oral anticoagulants. Curr Med Res Opin 2015; 31: 197-210.
  • 12 Prandoni P. Venous thromboembolism in 2013: the advent of the novel oral anticoagulants. Nat Rev Cardiol 2014; 11: 70-72.
  • 13 Lip GYH. et al. Non-vitamin k antagonist oral anticoagulants: An appeal for consensus on terminology. Chest 2014; 145: 1177-1178.
  • 14 Harder S, Graff J. Novel oral anticoagulants: clinical pharmacology, indications and practical considerations. Eur J Clin Pharmacol 2013; 69: 1617-1633.
  • 15 Jackson II LR, Becker RC. Novel oral anticoagulants: pharmacology, coagulation measures, and considerations for reversal. J Thromb Thrombol 2014; 37: 380-391.
  • 16 Beyer-Westendorf J, Ageno W. Benefit-risk profile of non-vitamin K antagonist oral anticoagulants in the management of venous thromboembolism. Thromb Haemost 2015; 113: 231-246.
  • 17 Hulle T. 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 metaαanalysis. J Thromb Haemost 2014; 12: 320-328.
  • 18 Konstantinides SV. et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35: 3033-3069 69a-69k.
  • 19 Enden T. et al. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet 2012; 379: 31-38.
  • 20 Vedantham S. et al. Rationale and design of the ATTRACT Study: a multicenter randomized trial to evaluate pharmacomechanical catheter-directed thrombolysis for the prevention of postthrombotic syndrome in patients with proximal deep vein thrombosis. Am Heart J 2013; 165: 523-530 e3.
  • 21 ten Cate H. DUTCH CAVA-trial: CAtheter Versus Anticoagulation Alone for Acute Primary (Ilio)Femoral DVT. Available at https://clinicaltrials.gov/ct2/show/NCT00970619 Accessed March 17, 2015.
  • 22 Bashir R. et al. Comparative outcomes of catheter-directed thrombolysis plus anticoagulation vs anticoagulation alone to treat lower-extremity proximal deep vein thrombosis. J Am Med Assoc Intern Med 2014; 174: 1494-1501.
  • 23 Konstantinides S. et al. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002; 347: 1143-1150.
  • 24 Meyer G. et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014; 370: 1402-1411.
  • 25 Chatterjee S. et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial haemorrhage: a meta-analysis. J Am Med Assoc 2014; 311: 2414-2421.
  • 26 Akwaa F, Spyropoulos AC. The potential of target-specific oral anticoagulants for the acute and long-term treatment of venous thromboembolism. Curr Med Res Opin 2014; 30: 2179-2190.
  • 27 Spyropoulos AC. Outpatient-based treatment protocols in the management of venous thromboembolic disease. Am J Manag Care 2000; 06 (Suppl. 20) S1034-S1044.
  • 28 Caplin DM. et al. Quality improvement guidelines for the performance of inferior vena cava filter placement for the prevention of pulmonary embolism. J Vasc Interv Radiol 2011; 22: 1499-1506.
  • 29 Group PS. Eight-Year Follow-Up of Patients With Permanent Vena Cava Filters in the Prevention of Pulmonary Embolism The PREPIC (Prévention du Risque d’Embolie Pulmonaire par Interruption Cave) Randomized Study. Circulation 2005; 112: 416-422.
  • 30 Stein PD. et al. Impact of vena cava filters on in-hospital case fatality rate from pulmonary embolism. Am J Med 2012; 125: 478-484.
  • 31 Minocha J. et al. Improving inferior vena cava filter retrieval rates: impact of a dedicated inferior vena cava filter clinic. J Vasc Interv Radiol 2010; 21: 1847-1851.
  • 32 Othieno R. et al. Home versus in-patient treatment for deep vein thrombosis. Cochrane Database Syst Rev 2007; 18: CD003076.
  • 33 Agnelli G. et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363: 2499-2510.
  • 34 Agnelli G. et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369: 799-808.
  • 35 Hokusai VTE Investigators, Buller HR. et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369: 1406-1415.
  • 36 Investigators E-P, Buller HR. et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366: 1287-1297.
  • 37 Schulman S. et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 2014; 129: 764-772.
  • 38 Schulman S. et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361: 2342-2352.
  • 39 Piran S. et al. Outpatient treatment of symptomatic pulmonary embolism: a systematic review and meta-analysis. Thromb Res 2013; 132: 515-519.
  • 40 Kovacs MJ. et al. Ambulatory management of pulmonary embolism: a pragmatic evaluation. J Thromb Haemost 2010; 08: 2406-2411.
  • 41 Wicki J. et al. Predicting adverse outcome in patients with acute pulmonary embolism: a risk score. Thromb Haemost 2000; 84: 548-552.
  • 42 Aujesky D. et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Resp Crit Care Med 2005; 172: 1041-1046.
  • 43 Aujesky D, lmonary embolism. Eur Heart J 2006; 27: 476-481.
  • 44 Murugappan M. et al. Home Management Exclusion (HOME) criteria for initial treatment of acute pulmonary embolism. International Conference of the American Thoracic Society 2008; 2008.
  • 45 Nendaz M. et al. Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism. Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE). Thromb Haemost 2014; 111: 531-538.
  • 46 Middeldorp S. et al. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev 2014; 08: CD001367.
  • 47 Galanis T. et al. The new oral anticoagulants for the treatment of venous thromboembolism: a new paradigm shift in antithrombotic therapy. Curr Ther Res Clin Exp 2014; 76: 76-83.
  • 48 Kakkos SK. et al. Editor’s Choice – efficacy and safety of the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban in the treatment and secondary prevention of venous thromboembolism: a systematic review and meta-analysis of phase III trials. Eur J Vasc Endovasc Surg 2014; 48: 565-575.
  • 49 Yeh CH. et al. Evolving use of new oral anticoagulants for treatment of venous thromboembolism. Blood 2014; 124: 1020-1028.
  • 50 Bacchus F, Schulman S. Clinical experience with the new oral anticoagulants for treatment of venous thromboembolism. Arterioscler Thromb Vasc Biol 2015; 35: 513-519.
  • 51 Lega JC. et al. Consistency of safety profile of new oral anticoagulants in patients with renal failure. J Thromb Haemost 2014; 12: 337-343.
  • 52 Saposnik G. et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke 2011; 42: 1158-1192.
  • 53 Kearon C. Influence of hereditary or acquired thrombophilias on the treatment of venous thromboembolism. Curr Opin Hematol 2012; 19: 363-370.
  • 54 Siegal DM, Cuker A. Reversal of target-specific oral anticoagulants. Drug Discov Today 2014; 19: 1465-1470.
  • 55 Siegal DM. et al. How I treat target-specific oral anticoagulant–associated bleeding. Blood 2014; 123: 1152-1158.
  • 56 Suryanarayan D, Schulman S. Potential antidotes for reversal of old and new oral anticoagulants. Thromb Res 2014; 133 (Suppl. 02) S158-S166.
  • 57 Wu C. et al. Case fatality of bleeding and recurrent venous thromboembolism during, initial therapy with direct oral anticoagulants: a systematic review. Thromb Res 2014; 134: 627-632.
  • 58 Kang N, Sobieraj DM. Indirect treatment comparison of new oral anticoagulants for the treatment of acute venous thromboembolism. Thromb Res 2014; 133: 1145-1151.
  • 59 Chai-Adisaksopha C. et al. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood 2014; 124: 2450-2458.
  • 60 Loffredo L. et al. Impact of new oral anticoagulants on gastrointestinal bleeding in atrial fibrillation: A meta-analysis of interventional trials. Digest Liver Dis. 2015. Epub ahead of print
  • 61 Prins MH. et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEINDVT and PE randomized studies. Thromb J 2013; 11: 21.
  • 62 Rajasekhar A, Streiff MB. Vena cava filters for management of venous thromboembolism: a clinical review. Blood Rev 2013; 27: 225-241.
  • 63 Ray Jr CE, Prochazka A. The need for anticoagulation following inferior vena cava filter placement: systematic review. Cardiovasc Interv Radiol 2008; 31: 316-324.
  • 64 Muriel A. et al. Survival effects of inferior vena cava filter in patients with acute symptomatic venous thromboembolism and a significant bleeding risk. J Am Coll Cardiol 2014; 63: 1675-1683.
  • 65 Rottenstreich A. et al. Patterns of use and outcome of Inferior vena cava (IVC) filters in a tertiary care setting. Eur J Haematol. 2015. Epub ahead of print
  • 66 Rajasekhar A. Inferior vena cava filters: current best practices. J Thromb Thrombolysis 2015; 39: 315-327.
  • 67 Paikin JS. et al. Effectiveness and safety of combined antiplatelet and anticoagulant therapy: a critical review of the evidence from randomized controlled trials. Blood Rev 2011; 25: 123-129.
  • 68 Hohnloser SH. et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation 2012; 125: 669-676.
  • 69 Cook D. et al. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med 2011; 364: 1305-1314.
  • 70 Harel Z. et al. Comparisons between novel oral anticoagulants and vitamin K antagonists in patients with CKD. J Am Soc Nephrol 2014; 25: 431-442.
  • 71 Dong BR. et al. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev 2009; 03: CD004437.
  • 72 Pauli RM. et al. Association of congenital deficiency of multiple vitamin K–dependent coagulation factors and the phenotype of the warfarin embryopathy: clues to the mechanism of teratogenicity of coumarin derivatives. Am J Hum Genet 1987; 41: 566-583.
  • 73 Armstrong EM. et al. Pregnancy-Related Venous Thromboembolism. J Pharm Pract 2014; 27: 243-252.
  • 74 Bates SM. Pregnancy-associated venous thromboembolism: prevention and treatment. Semin Hematol 2011; 48: 271-284.
  • 75 Lee AY. 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: 146-153.
  • 76 Lee AYY. et al. A Randomized Trial of Long-Term Tinzaparin, a Low Molecular Weight Heparin (LMWH), Versus Warfarin for Treatment of Acute Venous Thromboembolism (VTE) in Cancer Patients – the CATCH Study. Blood. 2014: 124 Epub ahead of print
  • 77 Vedovati MC. et al. Direct oral anticoagulants in patients with VTE and cancer: a systematic review and meta-analysis. Chest 2015; 147: 475-483.
  • 78 Kelton JG. et al. Nonheparin anticoagulants for heparin-induced thrombocytopenia. N Engl J Med 2013; 368: 737-744.
  • 79 Linkins L-A. et al. Treatment and Prevention of Heparin-Induced ThrombocytopeniaTreatment of HITAntithrombotic Therapy and Prevention of Thrombosis: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (Suppl. 02) e495S-e530S.
  • 80 Cuker A. et al. Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants. J Am Coll Cardiol 2014; 64: 1128-1139.
  • 81 Diepstraten J. et al. Population pharmacodynamic model for low molecular weight heparin nadroparin in morbidly obese and non-obese patients using anti-Xa levels as endpoint. Eur J Clin Pharmacol 2015; 71: 25-34.
  • 82 van Dongen CJ. et al. Once versus twice daily low molecular weight heparin for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev 2005; 03: CD003074.
  • 83 Douketis JD. et al. Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy. Arch Intern Med 2000; 160: 3431-3436.
  • 84 Kearon C. A conceptual framework for two phases of anticoagulant treatment of venous thromboembolism. J Thromb Haemost 2012; 10: 507-511.
  • 85 Linkins L-A. et al. Clinical Impact of Bleeding in Patients Taking Oral Anticoagulant Therapy for Venous Thromboembolism. A Meta-Analysis Ann Intern Med 2003; 139: 893-900.