New Anticoagulants for Venous Thromboembolism

Becattini C, Agnelli G.
Treatment of Venous Thromboembolism With New Anticoagulant Agents. J Am Coll Cardiol 2016;67:1941-1955.

The following are 10 key points to remember from this review on the use of new anticoagulant (NOAC, also known as direct oral anticoagulants) agents for treatment of venous thromboembolism (VTE):

  1. VTE is a common disease with a high risk for recurrence, death, and late sequela. One-year case fatality rates approach 23%. These complications account for substantial health care costs.
  2. Anticoagulants are the mainstay of treatment for VTE, which consists of deep vein thrombosis and pulmonary embolism. All patients require a minimum of 3 months of anticoagulant therapy. Select patients with unprovoked VTE may benefit from extended anticoagulation to further reduce the risk of recurrence.
  3. NOACs can be administered with fixed doses, without frequent laboratory monitoring, and without frequent dose adjustment. Additionally, rivaroxaban and apixaban do not require initial heparin therapy and can be used as monotherapy for patients with acute VTE.
  4. Each of the NOACs is, at least in part, renally cleared. Therefore, appropriate NOAC dosing should be adjusted for renal function, as estimated using the Cockcroft-Gault equation. In patients with a chronic kidney disease who are treated with a NOAC, renal function should be checked at least twice per year.
  5. In phase III clinical trials, the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitor (dabigatran) were noninferior and likely safer than the combination of heparin and vitamin K antagonist (VKA, usually warfarin) for acute VTE patients. No direct head-to-head studies of the NOACs have been reported in VTE patients.
  6. Elderly patients (≥75 years) may experience a significant reduction in VTE recurrence risk and major bleeding risk with NOAC therapy as compared to warfarin.
  7. Patients with cancer and intermediate- to high-risk pulmonary embolism patients were under-represented in most of the phase III trials, and therefore, management strategies are less clear.
  8. No data are currently available for the use of NOACs in pregnancy, breast-feeding, or children.
  9. NOACs have the potential to facilitate outpatient treatment of acute deep vein thrombosis and low-risk pulmonary embolism. Similarly, NOACs may facilitate a shorter hospital stay for acute VTE patients.
  10. In NOAC-treated patients who experience major bleeding, use of idarucizumab can rapidly reverse dabigatran’s anticoagulant effect. Andexanet will likely provide similar effects for the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), but has yet to be approved by the Food and Drug Administration or European Medicines Agency.

Clinical Topics: Anticoagulation Management, Geriatric Cardiology, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: Anticoagulants, Antithrombins, Factor Xa Inhibitors, Geriatrics, Heparin, Neoplasms, Primary Prevention, Pulmonary Embolism, Renal Insufficiency, Chronic, Venous Thromboembolism, Venous Thrombosis, Vitamin K, Warfarin

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