Lipid-Lowering and Antihypertensive Drugs on Aortic Disease Risk: Insights from Mendelian Randomization Analysis and Real-World Pharmacovigilance Data

Abstract Objective To assess the impact of lipid-lowering drugs (LLDs) and antihypertensive drugs on the risk of aortic diseases. Methods Mendelian randomization was utilized to analyze data from 500,000 participants in the UK Biobank to evaluate the effects of statins, PCSK9 inhibitors (PCSK9i), beta-blockers, and calcium channel blockers on the risks of thoracic aortic aneurysm (TAA), abdominal aortic aneurysm (AAA), and aortic dissection (AD) using genetic variants as proxies. Real-world pharmacovigilance data from the FAERS database was used. Results PCSK9i and statins significantly reduced the risks of aortic aneurysms and AD, respectively. Furthermore, the two LLDs reduced the risk of aortic diseases through certain metabolites. Meanwhile, real-world pharmacovigilance reports also indicated a low incidence of aortic diseases with PCSK9i and statin treatment. Conclusion LLDs, particularly statins and PCSK9i, significantly protect against aortic diseases, providing a scientific basis for preventing and treating aortic diseases.