Abstract
BACKGROUND: Abdominal aortic aneurysm (AAA) is a life-threatening condition with no proven pharmacological treatment to halt its progression. While animal models offer insights into pathophysiology and drug response, clinical translation remains limited. METHODS: We conducted a systematic review of repurposed drugs, classified by Anatomical Therapeutic Chemical (ATC) codes, tested in animal models for their effects on AAA progression. Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and a PROSPERO-registered protocol (CRD42024323430), we screened 14,127 articles and included 144 studies across 13 of the 14 ATC categories. RESULTS: Most drug classes, particularly cardiovascular, metabolic, and immunomodulatory agents-including statins, angiotensin II receptor blockers (ARBs), metformin, and rapamycin-showed a reduced aneurysm diameter. However, high heterogeneity in models, treatment timing, and methodological shortcomings, including a lack of blinding and power calculations, limit translational value. The predominance of positive findings suggests potential publication bias. CONCLUSIONS: Nevertheless, drugs effective post-aneurysm initiation may offer the greatest clinical promise. Our findings underscore the need for standardized, high-quality, preclinical research to support future human trials.