Prevention & lipidsCohort study

PCSK9 Inhibitors and Risk of Aortic Stenosis in Atherosclerotic Cardiovascular Disease

JACC AdvPublished

  • retrospective new-user cohort study
  • 1:1 propensity score matching
  • TriNetX

Authors' conclusion

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.

Study context

Population
Adults aged ≥60 years with atherosclerotic cardiovascular disease (ASCVD) receiving statins from January 1, 2015, to August 31, 2025patients in each group after 1:1 matching
Participants
22,924 adults
Exposure
PCSK9is were compared with statin-only users after 1:1 propensity score matching
  • PCSK9isn = 22,924
  • statin-only usersn = 22,924reference
Outcome
New-onset aortic stenosis (AS)
Follow-up
Within 5 years

Main finding

As reported in the abstract

Hazard ratio

0.87

95% CI 0.78–0.97

P = 0.012

PCSK9is vs statin-only users
HR 0.87 (95% CI 0.78–0.97); P = 0.012

Observational data: associations, not effects.

Secondary outcomes

All-cause mortality and heart failure exacerbation (HFE)

PCSK9is use was associated with a lower risk of all-cause mortality and HFE

Aortic valve replacement

Aortic valve replacement reduction was not significant

Subgroup analyses

Statistically significant interaction was observed only for chronic kidney disease and heart failure

Original publication

PCSK9 Inhibitors and Risk of Aortic Stenosis in Atherosclerotic Cardiovascular Disease. JACC Adv. Published 11 September 2026. doi:10.1016/j.jacadv.2026.103233

Summarised from the published abstract; every number is checked against it