Association of PCSK9 inhibitors with risk of nonmelanoma skin cancer: a retrospective cohort study.

Background: Growing evidence has shown that cholesterol metabolism abnormalities involve carcinogenesis. Proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors have been reported to inhibit tumor progression and prevent ultraviolet-related skin damage.

Objective: To investigate the association of PCSK9 inhibitors with the risk of nonmelanoma skin cancer (NMSC).

Methods: This retrospective cohort study analyzed data from the US Collaborative Network in the TriNetX database. Adults aged ≥40 years with atherosclerotic cardiovascular disease (ASCVD) under statin therapy between 2016 and 2022 were identified. A target trial design was used to compare the risk of NMSC, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), among patients additionally treated with PCSK9 inhibitors or continuing statin therapy (the control group). Each head-to-head comparison involved propensity score matching. Hazard ratios (HRs) were estimated using Cox proportional hazard models. Stratified analyses based on age, sex, Fitzpatrick skin type, and immune status were also performed.

Results: A total of 73,636 patients with ASCVD were analyzed. Compared with the control group, the ASCVD patients initiating PCSK9 inhibitors were associated with lower risks of NMSC (HR: 0.78; 95%CI: 0.71-0.87), BCC (HR: 0.78; 95%CI: 0.69-0.89), and cSCC (HR: 0.79; 95%CI: 0.67-0.93). Subanalyses revealed the reduced risk of NMSC observed with each PCSK9 inhibitor, namely, evolocumab and alirocumab. Stratified analyses showed similar results among patients aged 65-79 years, those more than 80 years, and male patients.

Conclusions: Our study indicated ASCVD patients with PCSK9 inhibitors have a lower risk of incident NMSC than those without PCSK9 inhibitors.