Association of PCSK9 inhibitors versus statins with cancer incidence: a target trial emulation

BACKGROUND: The relationship between PCSK9 inhibitors (PCSK9i) and cancer incidence remains poorly understood. This study is to investigate the association between PCSK9i use and cancer risk compared to statin therapy. METHODS: We conducted a retrospective cohort study using target trial emulation principles on de-identified electronic health records from the TriNetX network (July 2015 – June 2023). Adults with indications for lipid-lowering therapy who initiated PCSK9i (alirocumab, evolocumab, or inclisiran) or statins (no prior statin use) were included. New PCSK9i users were propensity-score matched 1:1 with new statin users. The primary outcome was the incidence of any malignant neoplasm, defined by ICD-10 codes C00–C97, over a 5-year follow-up period. RESULTS: A total of 43,935 PCSK9i users and 6,127,401 statin users were identified; after matching, 43,933 PCSK9i users were compared with 43,933 statin users. PCSK9i use was associated with a significantly lower risk of overall cancer (HR 0.804, 95% CI 0.760–0.850) compared to statin use. Notably, PCSK9i users had lower incidence of cancers of the digestive organs (HR 0.647, 95% CI 0.548–0.763), respiratory and intrathoracic organs (HR 0.691, 95% CI 0.578–0.827), melanoma and other skin cancers (HR 0.789, 95% CI 0.704–0.885), female genital organs (HR 0.735, 95% CI 0.558–0.968), urinary tract (HR 0.719, 95% CI 0.590–0.875), and ill-defined sites (HR 0.660, 95% CI 0.578–0.755) compared to statin users. CONCLUSIONS: This study revealed a significant association between PCSK9i use and reduced cancer incidence compared with statin use, suggesting effects beyond lipid regulation.