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DOACs Update

WHAT ARE THE DOACs?

The term direct oral anticoagulants (DOACs, previously NOAC for novel oral anticoagulants) describes two classes of medications: direct thrombin inhibitor and factor Xa inhibitors. These drugs provide alternative oral anticoagulation options for management in non-valvular atrial fibrillation and venous thromboembolism without the need for specific dietary restrictions or monitoring typically required for patients taking vitamin K antagonists.

DrugClassUsesEvidenceHalf-LifeDabigatran (Pradaxa)-Direct thrombin inhibitor -First oral direct thrombin inhibitor -Approved by FDA in 2010-AFib* -DVT/PE -VTE prophylaxis with hip replacement surgery-Non-inferior in 110mg dose (not available in US) -Superior to warfarin in 150mg dose for stroke and systemic embolism in atrial fibrillation112-17hRivaroxaban (Xarelto)-Factor Xa inhibitor -First oral factor Xa inhibitor -Approved by FDA in 2011-AFib* -DVT/PE2 -VTE prophylaxis with knee or hip replacement surgeryNon-inferior to warfarin for prevention of stroke and systemic embolism in atrial fibrillation35-9hApixaban (Eliquis)-Factor Xa inhibitor -Approved in 2014-AFib* -DVT/PE -VTE prophylaxis with knee or hip replacement surgeryNon-inferior and superior to warfarin for stroke and systemic embolism in atrial fibrillation412hEdoxaban (Savaysa)-Direct Xa inhibitor -Newest oral anticoagulant -Approved in 2015-AFib* -DVT/PE after 5-10 days parenteral anticoagulationNon-inferior to warfarin for stroke or systemic embolism in atrial fibrillation510-14h

* Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation

THE CHALLENGE

When compared with the vitamin K antagonist warfarin, direct oral anticoagulants require less monitoring and most can be initiated without a bridge with parenteral anticoagulants. These benefits are also part of the risk of the DOACs; there are few widely accepted and available laboratory tests to assess the activity level of these medications, and management strategies for bleeding complications are unclear.

DOACs have a wider therapeutic window than warfarin, but the risk of bleeding with these drugs remains.1,3,6 Dabigatran, rivaroxaban, apixaban, and edoxaban all have significant renal excretion, so the risk of bleeding increases in the setting of renal impairment.6

When a patient presents with severe hemorrhage while taking one of these medications, certain laboratory assays may be helpful to assess increased systemic drug concentration or activity:

  1. For dabigatran: elevated aPTT may be useful, but a normal test does not exclude a supratherapeutic concentration.7 Thrombin time (TT) and ecarin clotting time (ECT) provide a better assessment of anticoagulant effect, but these tests are not readily available for clinical use.7,8

  2. For rivaroxaban and apixaban: PT may correlate to the plasma concentration. Chromogenic antifactor Xa assay is more useful, but is not widely available in the clinical setting.7AdvantagesDisadvantagesNo monitoring of levels is requiredReadily available labs are unreliable to quantify drug effectEasy dosing schedule for most patientsCostLower incidence of intracranial hemorrhageSimilar or higher incidence of GI bleeding (Post-marketing data)Wider therapeutic index, patient diet has less impactRenally excreted so increased bleeding risk if acute kidney injury/renal failureAvailable reversal strategies (PCC)Low quality evidence for specific reversal strategies in bleeding patients

In the next post, we will talk about what happens when bleeding occurs on DOACs and suggest a guideline for management in the emergency department.

Part II

#anticoagulation #Hematologic