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.
Abnormalities in the body’s metabolism of a type of fat called cholesterol can lead to the development of skin cancer. Certain drugs that lower the levels of fats (‘lipids’) in the body may reduce the risk of a person developing a type of skin cancer called non-melanoma skin cancer (or ‘NMSC’ for short). These drugs include a type of medication called ‘PCSK9 inhibitors’. It is not known if giving PCSK9 inhibitors to patients already taking a type of drug called a ‘statin’ to lower their cholesterol has a beneficial effect in reducing their risk of developing NMSC. We investigated the association of PCSK9 inhibitors with NMSC. We did this using data from the USA. We compared the risk of developing NMSC in adults with heart disease taking PCSK9 inhibitors plus a statin with people who were only taking statins. A total of 73,236 people were included. We found that patients who took PCSK9 inhibitors as well as a statin had less risk of developing NMSC than people who only took a statin. Our findings suggest that using PCSK9 inhibitors decreases the risk of a person developing NMSC. The preventive role of PCSK9 inhibitors is worth considering in clinical practice.
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