Mechanical heart valve thrombosis and novel oral anticoagulants: a word of caution
Bibliographic record
Abstract
not surprising that even vitamin K antagonists are prescribed to achieve different therapeutic levels in patients with AF versus mechanical heart valves, particularly in the mitral position. Therefore, the dosing of the new anticoagulants will likely have to be tailored to the indication for anticoagulation. There have only been a few preclinical models investigating the possible role of either dabigatran or rivaroxaban in mechanical valve thrombo-prophylaxis. McKellar and colleagues used an in vivo swine model whereby a modified bileaflet mechanical valved conduit (St Jude Masters Series, St Jude Medical, Inc., MN, USA) was implanted to bypass the ligated, native descending thoracic aorta to compare the amount of valve thrombosis at 30 days in a control group (no anticoagulation), a clinical group control (enoxaparin 2 mg/kg twice daily) and experimental group (dabigatran 20 mg/kg twice daily) [7]. Their short-term results demonstrated that dabigatran was as effective as enoxaparin in preventing modified heterotopic mechanical aortic valve thrombosis. There was no mortality difference between all groups. Conversely, Schomburg and colleagues used an orthotopic swine mechanical mitral valve replacement model (27 mm Carbomedics OptiFormTM Mitral Valve, Sorin, Vancouver, Canada), comparing control group (no anticoagulation), clinical control group (warfarin therapy) and experimental group (dabigatran therapy at 20 mg/kg twice daily) and demonstrated a significant survival benefit of the use of dabigatran when compared with warfarin therapy. However, thrombus presence at necropsy was found to be twice as high in the dabigatran group (80%) versus the warfarin group (40%; p = 0.2) [8]. Although in vitro studies demonstrated similar effectiveness of dabigatran or rivaroxaban to unfractionated heparin and low molecular weight heparin in Oral anticoagulant therapeutic options are currently expanding, not only in drug types, but their clinical indications. Dabigatran etexilate (Pradaxa) is a direct thrombin (IIa) inhibitor that has been approved for prevention of embolic stroke related to nonvalvular atrial fibrillation (AF) following results from the RE-LY trial, a study comparing dabigatran (110 or 150 mg twice daily) with warfarin in patients with nonvalvular AF, were published in 2009 [1,2]. RE-LY demonstrated similar rates of thromboembolic events in low-dose dabigatran versus warfarin, while higher doses of dabigatran showed even fewer thromboembolic events [2]. Along with other trials investigating new oral anticoagulants in patients with nonvalvular AF (RE-LY [2], ARISTOTLE [3], AVERROES [4], ROCKET-AF [5]), current national guidelines now have recommendations for the use of dabigatran, apixaban and rivaroxaban for prevention of stroke in nonvalvular AF patients and prevention of deep vein thrombosis following orthopedic surgery [1,6]; however, there is little information regarding the use of these medications in mechanical valve thromboprophylaxis. Thus, off-label use of these new drugs could lead to catastrophic complications, since their mechanism of anticoagulation does not mirror that of vitamin K antagonists.
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How this classification was reachedexpand
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".