New thrombin and factor Xa inhibitors for primary and secondary prevention of ischaemic stroke
Bibliographic record
Abstract
Atrial fibrillation is a major risk factor for first and recurrent ischaemic stroke, and anticoagulation, mainly by use of coumarin medications, is an effective strategy for reducing ischaemic stroke occurrence in these patients. However, the coumarin medications have disadvantages. Over the past decade, important strides have been made towards developing improved anticoagulant medications. This review discusses these new developments and what they mean for the future of primary and secondary ischaemic stroke prevention in patients with atrial fibrillation. Relevant papers were identified with electronic searches of the Medline and EMBASE databases. Ongoing trials were checked using the Trials Results Centre website. The direct thrombin inhibitors, and the factor Xa inhibitors are the two major new anticoagulant drug classes under development at present. In phase III trials, dabigatran and rivaroxaban demonstrated at least as good performance as warfarin at reducing the rate of ischaemic stroke, systemic embolus, and haemorrhagic ischaemic stroke, whilst maintaining a comparable or lower rate of major bleeding events. Drug level monitoring was not required due to stable pharmacodynamics. AZD0837, apixaban, YM-150, edoxaban and betrixaban all showed promising results in phase II trials, as did S35972 in animal, in vitro and ex vivo models. The future of these new anticoagulants looks encouraging, although there are still some significant challenges to overcome. We need to consider the accumulation of long-term safety and efficacy data, and the development of effective means of reversal of anticoagulation for the direct thrombin inhibitors and factor Xa inhibitors.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.010 | 0.002 |
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 source (direct Gemma or distilled Codex), 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".