Association of proprotein convertase subtilisin/kexin type-9 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 tumour progression and prevent ultraviolet-related skin damage.

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

Methods: This retrospective cohort study analysed 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), in patients also treated with PCSK9 inhibitors or continuing statin treatment (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 analysed. Compared with the control group, patients with ASCVD initiating PCSK9 inhibitors had lower risks of developing NMSC [HR 0.78, 95% confidence interval (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 a reduced risk of NMSC with each PCSK9 inhibitor, namely evolocumab and alirocumab. Stratified analyses showed similar results in patients aged 65-79 years, those older than 80 years and in men.

Conclusions: Our study indicated that patients with ASCVD taking PCSK9 inhibitors have a lower risk of incident NMSC than those not taking PCSK9 inhibitors.