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

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. 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. 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. This study revealed a significant association between PCSK9i use and reduced cancer incidence compared with statin use, suggesting effects beyond lipid regulation.