Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation

Kevin Lao, Mercer University College of Pharmacy

The 2016 European Society of Cardiology guidelines recommend a short period of triple therapy (oral anticoagulant [OAC], aspirin, clopidogrel) for patients with atrial fibrillation (AFib) undergoing percutaneous coronary intervention (PCI) with a stent placement. [1]

Contrary to the European guidelines, the American Heart Association guidelines state that it may be reasonable to use clopidogrel with OAC without aspirin in AFib patients with CHA2DS2-VASc score ≥ 2 following PCI based on evidence that showed higher rates of bleeding with triple therapy. [2] Additionally, one previous trial has shown that dual therapy (warfarin + clopidogrel [P2Y12 inhibitor]) was associated with lower incidence of bleeding without increased rates of stent thrombosis in PCI patients compared to triple therapy. [3]

With the availability of the new oral anticoagulant (NOAC), some evidence suggests that NOAC, instead of warfarin, with a P2Y12 inhibitor (i.e. clopidogrel) may be an effective thromboprophylaxis in PCI patients. Therefore, the RE-DUAL PCI trial aimed to compare the efficacy and safety of dual therapy composed of dabigatran and P2Y12 inhibitor among patients with AFib undergoing PCI. [4]

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Praxbind® : Clinical Efficacy

Akpan Anani, Mercer University College of Pharmacy

While oral anticoagulants are used for the prevention or treatment of thrombotic events, certain life-threatening scenarios may warrant interventions in which anticoagulant reversal is needed to achieve hemostasis. Consequently, the availability and efficacy of reversal agents can have a large impact on the decision making of healthcare providers in regards to the anticoagulant therapy regimen being utilized by patients. Pradaxa® (dabigatran) is an oral anticoagulant approved in the U.S. in 2010 for the treatment and prevention of different thrombotic events. [1] Conversely, Praxbind® (idarucizumab) is an aptly named humanized monoclonal antibody fragment that binds to dabigatran and reverses its anticoagulant activity. [2] Idarucizumab has been licensed in numerous countries (first approved in the U.S. in 2015) [3] based on preliminary results from the first 90 patients enrolled in the Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD) trial. [4]

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RE-CIRCUITing Anticoagulants for Catheter Ablation

Sandy Liu, Mercer University College of Pharmacy

Catheter ablation of atrial fibrillation is typically performed with uninterrupted anticoagulation with warfarin or interrupted non-vitamin K antagonist (NVKA) oral anticoagulant therapy.  Due to the lack of controlled data, it is unknown whether uninterrupted anticoagulation with a NVKA agent, such as dabigatran, is a safer option than warfarin. [1]

Warfarin is a vitamin K antagonist that competitively inhibits the subunit 1 of the multi-unit vitamin K epoxide reductase (VKOR) complex, thus depleting functional K reserves and reducing synthesis of active clotting factors. [2]  Conversely, dabigatran is a reversible, direct thrombin inhibitor that inhibits both free and fibrin-bound thrombin, thereby preventing thrombin-mediated effects, including cleavage of fibrinogen to fibrin monomers, inhibition of thrombin-induced platelet aggregation and activation of factors V, VIII, XI and XIII. [3]

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