Tyrosine kinase inhibitors targeting vascular endothelial growth factor and the risk of aortic dissection—A pharmacovigilance analysis
Bibliographic record
Abstract
There are concerns by the United States Food and Drug Administration (FDA) regarding a potential link between tyrosine kinase inhibitors targeting vascular endothelial growth factor (VEGF-TKIs) and the risk of aortic dissection. Elevation of blood pressure induced by VEGF-TKIs has been discussed as part of the pathomechanism. To address this important safety issue, we conducted a large pharmacovigilance study assessing the risk of aortic dissection reporting associated with the use of VEGF-TKIs, thereby exploring the role of blood pressure. We queried the FDA Adverse Event Reporting System from 2004 to 2019 for reports including VEGF-TKIs and aortic dissection and estimated reporting odds ratios (RORs) and 95% confidence intervals (CIs) of aortic dissection associated with the use of VEGF-TKIs. Secondary analyses stratified by the strength of blood pressure elevation (≥10 mmHg vs. <10 mmHg increased systolic or diastolic bloods pressure) and pre-existing arterial hypertension. There were 81 reports of aortic dissection related to VEGF-TKIs during the study period. VEGF-TKIs were associated with an increased risk of aortic dissection reporting (ROR, 4.31; 95% CI, 3.43 to 5.42). The risk was higher among compounds strongly increasing blood pressure (ROR, 5.33; 95% CI, 3.88 to 7.32) than among compounds moderately increasing blood pressure (ROR, 2.79; 95% CI, 1.83 to 4.27). Pre-existing arterial hypertension did not modify the association. Overall, our study showed an increased risk of aortic dissection reporting associated with the use of VEGF-TKIs. Blood pressure elevation seems to play a role in the pathophysiology of this adverse effect.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".