Pharmacologic Properties of the New Oral Anticoagulants: A Clinician-oriented Review with a Focus on Perioperative Management
Why this work is in the frame
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Bibliographic record
Abstract
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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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it