High-intensity statin therapy in aortic stenosis patients was associated with increased aortic valve calcification and a 30% increased rate of hospitalization for non-rheumatic aortic valve disease.
Observational
Does high-intensity statin therapy increase aortic valve calcification and hospitalization in patients with severe aortic stenosis?
High-intensity statin therapy may paradoxically promote aortic valve calcification and worsen clinical outcomes in patients with severe aortic stenosis, potentially mediated by increased PCSK9 secretion.
Effect estimate: 30% increased rate
Aortic stenosis (AS) is the most common valvular disease, characterized by progressive fibro-calcific remodeling of the aortic leaflets, leading to increased morbidity and mortality. It is now well known that statins influence the production of proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn is linked to calcification. Here, we found that statins significantly increased, in a dose dependent manner, both PCSK9 secretion and valve interstitial cell (VIC) calcification, in vitro. These effects were blunted by PCSK9 genetic knock-down or by PCSK9 antibody neutralization. In AS patients, contrast-enhanced computed tomography evaluation showed a higher aortic valve calcium (AVC) content in patients on high-intensity statins compared to low-intensity ones, with no significant difference between low-intensity statin and non-users. At follow-up, high-intensity statin users exhibited a higher annual AVC accumulation compared to low-intensity statins and non-users. In a real-world scenario, high-intensity statin therapy was associated with a 30 % increased rate of hospitalization for non-rheumatic aortic valve disease. Our findings highlight the need for further investigation into the intricate relationship between statin therapy and aortic valve health to identify the optimal lipid-lowering strategy in the management of patients at risk of developing or afflicted by AS.
Myasoedova et al. (2025) conducted an observational in Aortic stenosis. High-intensity statins vs. Low-intensity statins and non-users was evaluated on Hospitalization for non-rheumatic aortic valve disease (30% increased rate). High-intensity statin therapy in aortic stenosis patients was associated with increased aortic valve calcification and a 30% increased rate of hospitalization for non-rheumatic aortic valve disease.