Lipid-lowering and antihypertensive drugs on aortic disease risk: insights from Mendelian randomization analysis and real-world pharmacovigilance data

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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 analyse data from 500 000 participants in the UK Biobank to evaluate the effects of statins, PCSK9 inhibitors (PCSK9i), β-blockers, and calcium channel blockers on the risks of thoracic aortic aneurysm, abdominal aortic aneurysm, and aortic dissection (AD) using genetic variants as proxies. Real-world pharmacovigilance data from the FAERS (FDA Adverse Event Reporting System) database were 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.

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