Pharmacologic Properties of the New Oral Anticoagulants: A Clinician-oriented Review with a Focus on Perioperative Management
James D. Douketis
Affiliation: St. Joseph's Healthcare, Room F-544, 50 Charlton Ave East, Hamilton, ON, Canada, L8N 4A6.
The past decade has witnessed an explosion in the clinical development of new orally-administered anticoagulant drugs aimed at complementing vitamin K antagonists and heparins for the prevention and treatment of venous thromboembolism, for the prevention of stroke in patients with chronic atrial fibrillation, and for treatment of acute coronary syndromes. This review will focus on those new oral anticoagulants that are most relevant to the practicing clinician. These drugs consist of dabigatran, a direct thrombin inhibitor and rivaroxaban, a factor Xa inhibitor, both of which have been recently approved for clinical use. In addition, apixaban will be reviewed, which is another factor Xa inhibitor that is in the final stages of clinical development. The objectives of this review are: 1) to provide a clinician-oriented overview of the key pharmacokinetic and pharmacodynamic properties of dabigatran, rivaroxaban and apixaban; and 2) to consider the implications of these drugs pharmacologic properties in the perioperative setting for patients who require elective or urgent surgery, focusing on pre- and post-operative dosing, laboratory monitoring and reversal of anticoagulant effect.
Keywords: New anticoagulants, perioperative anticoagulation, pharmacokinetics, pharmacodynamics, Anticoagulants, vitamin K, heparins, thromboembolism, chronic atrial fibrillation, acute coronary syndromes, dabigatran, thrombin inhibitor, ri-varoxaban, Xa inhibitor, rivaroxaban, dabigatran etexilate, TAK 442, eribaxaban LY517717, DU 176b, YM 150, acenocoumarol, phenprocoumon, warfarin, fondaparinux, hirudin, lepirudin, argatroban, tartaric acid, cytochrome P-450, acylglucoronidases, creatinine, prothrombin, fibrinogen, ecarin clotting time, P-glycoprotein, CYP pathway, hepatic biliary excretion, anti-arrhythmic, verapamil, CYP-independent mechanisms, ketoconazle, vori-conazole, fluconazole, spinal/epidural anesthesia, bridging anticoagulation
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