High-signal drug assessment for drug-related aortic aneurysm and dissection rupture: Evidence from real-world databases and animal experiments

Xuezhen Xuan; Xuexing Xuan; Jia Li; Xin Guan; Wei Wang; Sichong Qian; Hongjia Zhang; Haiyang Li

doi:10.59717/j.xinn-med.2026.100225

The Innovation Medicine > 2026 Vol. 4 > No. 3 > 100225

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High-signal drug assessment for drug-related aortic aneurysm and dissection rupture: Evidence from real-world databases and animal experiments

1.
Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
2.
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China
3.
College of Basic Medical Sciences, Shandong University, Jinan 250012, China
4.
Department of Cardiovascular Medicine, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, China
5.
Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
6.
These authors contributed equally

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Corresponding authors: zhanghongjia722@ccmu.edu.cn (H.Z.); drqsc@mail.ccmu.edu.cn (S.Q.); wangweiocean@163.com (W.W.)
Received Date: December 09, 2025

Accepted Date: May 29, 2026

Published Online: May 31, 2026

The Innovation Medicine 4(3), https://doi.org/10.59717/j.xinn-med.2026.100225 | Cite this article

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PUBLIC SUMMARY
1. Aortic aneurysm and dissection may lead to fatal aortic rupture.
  
  We screened 40 high-signal related drugs from real-world databases and verified the risk with animal models.
  
  These drug signals do not confirm causality, and further research is needed to guide safe clinical medication.

ABSTRACT

ABSTRACT

Background: Aortic rupture represents the most critical complication of aortic aneurysm and dissection (AAD). Identifying and avoiding drugs associated with increased aortic rupture risk may provide immediate clinical benefits. Methods: Data from the FAERS and JADER databases (2004 Q1–2025 Q2) were analyzed. Clinical characteristics associated with adverse events of aortic rupture were summarized. Four disproportionality methods, reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were applied to detect adverse drug reaction signals. Drugs positive in all four methods were classified as high-signal. A time-to-onset analysis was conducted. Rivaroxaban was chosen as a representative drug for further investigation of its impact on aortic rupture risk in an AAD mouse model. Results: FAERS analysis identified 1,313 drug-associated AAD rupture reports involving 333 medications. Antithrombotic agents were most frequently implicated (247 cases, 18.8%), followed by Immunosuppressants (218 cases, 16.6%) and Antineoplastic agents (176 cases, 13.4%). Disproportionality analysis identified 40 drugs with high reporting signals for AAD rupture. Affected individuals were predominantly male (63.8%) and aged ≥65 years (74.0%). Reports and associated fatalities have increased in recent years, although overall mortality has declined. JADER provided 104 reports (17 drugs), consistent with FAERS findings except for the inclusion of SARS-CoV-2 mRNA vaccines. Animal experiments demonstrated that rivaroxaban did not increase AAD incidence but significantly elevated the aortic rupture risk. Conclusion: This study identified 40 high-signal drugs associated with AAD rupture, offering clinical references for safer drug usage. Further studies are necessary to clarify these risks.

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Xuan X., Xuan X., Li J., et al. (2026). High-signal drug assessment for drug-related aortic aneurysm and dissection rupture: Evidence from real-world databases and animal experiments. The Innovation Medicine 4:100225. https://doi.org/10.59717/j.xinn-med.2026.100225

Xuan X., Xuan X., Li J., et al. (2026). High-signal drug assessment for drug-related aortic aneurysm and dissection rupture: Evidence from real-world databases and animal experiments. The Innovation Medicine 4:100225. https://doi.org/10.59717/j.xinn-med.2026.100225

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High-signal drug assessment for drug-related aortic aneurysm and dissection rupture: Evidence from real-world databases and animal experiments

GRAPHICAL ABSTRACT

PUBLIC SUMMARY

ABSTRACT