Abstract

Non-vitamin K antagonist oral anticoagulants (NOACs) include dabigatran, which inhibits thrombin, and apixaban, betrixaban, edoxaban and rivaroxaban, which inhibit factor Xa. In large clinical trials comparing the NOACs with the vitamin K antagonist (VKA) warfarin, dabigatran, apixaban, rivaroxaban and edoxaban were at least as effective for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism, but were associated with less intracranial bleeding. In addition, the NOACs are more convenient to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. Consequently, the NOACs are now replacing VKAs for these indications, and their use is increasing. Although, as a class, the NOACs have a favourable benefit-risk profile compared with VKAs, choosing among them is complicated because they have not been compared in head-to-head trials. Therefore, selection depends on the results of the individual trials, renal function, the potential for drug-drug interactions and preference for once- or twice-daily dosing. In addition, several 'special situations' were not adequately studied in the dedicated clinical trials. For these situations, knowledge of the unique pharmacological features of the various NOACs and judicious cross-trial comparison can help inform prescription choices. The purpose of this position article is therefore to help clinicians choose the right anticoagulant for the right patient at the right dose by reviewing a variety of special situations not widely studied in clinical trials.

Highlights

  • The non-vitamin K antagonist oral anticoagulants (NOACs), which are known as the direct oral anticoagulants, include the direct thrombin inhibitor dabigatran, and the direct factor Xa (FXa) inhibitors apixaban, betrixaban, edoxaban and rivaroxaban

  • Dedicated clot-based assays, such as the diluted thrombin time (TT) and the ecarin clotting time, or chromogenic assays are recommended for measuring dabigatran levels; whereas chromogenic anti-FXa assays are the tests of choice to quantify the levels of the oral FXa inhibitors, such as apixaban, edoxaban, rivaroxaban or betrixaban.[41]

  • Andexanet alfa is approved by the Food and Drug Administration (FDA) and will be available soon; but until andexanet alfa or ciraparantag is available, 3-factor pro-thrombin complex concentrate (3FPCC) or 4-factor pro-thrombin complex concentrate (4FPCC) should be administered for reversal of oral FXa inhibitors in patients presenting with life-threatening bleeding

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Summary

14 Review Article

The Non-Vitamin K Antagonist Oral Anticoagulants in Heart Disease: Section V—Special Situations. Raffaele De Caterina1,2Ã Walter Ageno[3] Giancarlo Agnelli[4] Noel C. Chan[5] Hans-Christoph Diener[6] Elaine Hylek[7] Gary E. A. Verheugt[10] Gregory Y.

Introduction
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35 Æ 4 d Enoxaparin for 10 Æ 4 d
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