PCSK9 Inhibitor and Potential Decreased Risk of Neoplasms, Especially in Females: A Meta-Analysis

<b>Background</b>: Proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) has been reported to exhibit anti-neoplasm effects. However, the specific impacts remain uncertain. This study aims to evaluate the association between PCSK9i and the risk of neoplasm. <b>Methods</b>: Randomized controlled trials (RCTs) comparing PCSK9i with other lipid-lowering drugs or placebo in patients, which reported neoplasm events, were included. Data were sourced from PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and the Clinicaltrial.gov website from the inception to June 2024. The primary endpoint was the association between PCSK9i and the risk of overall neoplasm events. <b>Results</b>: A total of 37 RCTs with 108,430 participants were included. PCSK9i treatment was associated with a lower risk of neoplasm compared to non-users (RR = 0.92, 95% CI, 0.85 to 0.99, I² = 0%). Subgroup analysis revealed a more prominent risk reduction of overall neoplasm in studies with female-dominant populations (male percentage < 50%, RR = 0.47, 95% CI, 0.27 to 0.82, I² = 0%), with a significant subgroup differences (<i>p</i> = 0.02). Meta-regression analysis also suggested that the lower percentage of males was associated with a decreased risk of neoplasms (β = 0.018, 95% CI, 0.0063, 0.031, <i>p</i> = 0.002). Meanwhile, the decreased risk of neoplasms was independent of LDL-c reduction. <b>Conclusions</b>: PCSK9i therapy was associated with reduced risk of overall neoplasm, especially in female-dominant populations. The benefits for lower risk of neoplasm with PCSK9i treatment were independent of LDL-c reduction.