Key result
PCSK9 inhibitors linked to ~13% lower risk of new-onset aortic stenosis in statin-treated ASCVD.
Why the study?
Whether PCSK9 inhibitors are associated with lower incident aortic stenosis risk in statin-treated patients with ASCVD remains uncertain.
Does the addition of PCSK9 inhibitors to statin therapy reduce the risk of incident aortic stenosis in older adults with ASCVD?
Cohort (n=45,848)
Does the addition of PCSK9 inhibitors to statin therapy reduce the risk of incident aortic stenosis in older adults with ASCVD?
Answers are grounded in this paper and cite their sources.
In statin-treated older adults with ASCVD, PCSK9 inhibitor use is associated with a modestly lower 5-year incidence of new-onset aortic stenosis, generating hypotheses for future trials.
BACKGROUND: Atherosclerotic 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. OBJECTIVES: The objective of the study was to assess the association between PCSK9is use and incident AS in statin-treated patients with ASCVD. METHODS: Using 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. RESULTS: After 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. CONCLUSIONS: In 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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Wu et al. (2026) conducted a cohort in Atherosclerotic cardiovascular disease (ASCVD) (n=45,848). PCSK9 inhibitors vs. Statin-only users was evaluated on New-onset aortic stenosis within 5 years (HR 0.87, 95% CI 0.78-0.97, p=0.012). In statin-treated patients with ASCVD, PCSK9 inhibitor use was associated with a lower 5-year risk of new-onset aortic stenosis compared to statin-only use (HR 0.87; 95% CI 0.78-0.97; P=0.012).
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