The pleiotropic effects of antithrombotic drugs in the metabolic–cardiovascular–neurodegenerative disease continuum: impact beyond reduced clotting
Why this work is in the frame
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Bibliographic record
Abstract
Antithrombotic drugs are widely used for primary and secondary prevention, as well as treatment of many cardiovascular disorders. Over the past few decades, major advances in the pharmacology of these agents have been made with the introduction of new drug classes as novel therapeutic options. Accumulating evidence indicates that the beneficial outcomes of some of these antithrombotic agents are not solely related to their ability to reduce thrombosis. Here, we review the evidence supporting established and potential pleiotropic effects of four novel classes of antithrombotic drugs, adenosine diphosphate (ADP) P2Y12-receptor antagonists, Glycoprotein IIb/IIIa receptor Inhibitors, and Direct Oral Anticoagulants (DOACs), which include Direct Factor Xa (FXa) and Direct Thrombin Inhibitors. Specifically, we discuss the molecular evidence supporting such pleiotropic effects in the context of cardiovascular disease (CVD) including endothelial dysfunction (ED), atherosclerosis, cardiac injury, stroke, and arrhythmia. Importantly, we highlight the role of DOACs in mitigating metabolic dysfunction-associated cardiovascular derangements. We also postulate that DOACs modulate perivascular adipose tissue inflammation and thus, may reverse cardiovascular dysfunction early in the course of the metabolic syndrome. In this regard, we argue that some antithrombotic agents can reverse the neurovascular damage in Alzheimer's and Parkinson's brain and following traumatic brain injury (TBI). Overall, we attempt to provide an up-to-date comprehensive review of the less-recognized, beneficial molecular aspects of antithrombotic therapy beyond reduced thrombus formation. We also make a solid argument for the need of further mechanistic analysis of the pleiotropic effects of antithrombotic drugs in the future.
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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 | 0.007 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.006 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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