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Importance of Pharmacokinetic Profile and Variability as Determinants of Dose and Response to Dabigatran, Rivaroxaban, and Apixaban


Warfarin has been the mainstay oral anticoagulant (OAC) medication prescribed for stroke prevention in atrial fibrillation (AF) patients.
However, warfarin therapy is challenging because of marked interindividual variability in dose and response, requiring frequent monitoring and dose titration. These limitations have prompted the clinical development of new OACs (NOACs) that directly target the coagulation cascade with rapid onset/offset of action, lower risk for drug-drug interactions, and more predictable response. Recently, NOACs dabigatran (direct thrombin inhibitor), and rivaroxaban and apixaban (factor Xa [FXa] inhibitors) have gained regulatory approval as alternative therapies to warfarin. Though the anticoagulation efficacy of these NOACs has been characterized, differences in their pharmacokinetic and pharmacodynamic profiles have become a significant consideration in terms of drug selection and dosing.


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English
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Canadian Journal of Cardiology 29 (2013) S24eS33
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