ArticleJACC. Advances2026
PCSK9 Inhibitors and Risk of Aortic Stenosis in Atherosclerotic Cardiovascular Disease.
Article in JACC. Advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAtherosclerotic cardiovascular disease (ASCVD) and aortic stenosis (AS) share lipid-related mechanisms. Although statins have not slowed established AS progression in randomized trials, whether proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) are associated with lower incident AS risk remains uncertain.
objectivesThe objective of the study was to assess the association between PCSK9is use and incident AS in statin-treated patients with ASCVD.
methodsUsing TriNetX, we conducted a retrospective new-user cohort study of adults aged ≥60 years with ASCVD receiving statins from January 1, 2015, to August 31, 2025. PCSK9is were compared with statin-only users after 1:1 propensity score matching. The primary outcome was new-onset AS within 5 years; secondary outcomes included all-cause mortality, heart failure exacerbation (HFE), and aortic valve replacement.
resultsAfter 1:1 matching, 22,924 patients remained in each group. PCSK9is use was associated with a lower risk of AS (HR: 0.87; 95% CI: 0.78-0.97; P = 0.012), all-cause mortality, and HFE. Aortic valve replacement reduction was not significant. Subgroup analyses showed statistically significant interaction was observed only for chronic kidney disease and heart failure.
conclusionsIn statin-treated patients with ASCVD, PCSK9i use was associated with a modestly lower 5-year incidence of new-onset AS. Large mortality and HFE associations may reflect residual confounding and treatment-selection bias. These findings are hypothesis-generating.
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