Low-Density Lipoprotein Cholesterol Reduction with Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies in Women: A Systematic Review

Background Cardiovascular disease remains the leading cause of mortality among women worldwide and accounts for approximately one-third of all deaths globally. Elevated low-density lipoprotein cholesterol (LDL-C) is a well-established, causal, and modifiable risk factor in the development of atherosclerotic cardiovascular disease (ASCVD). Methods This review was conducted in accordance with PRISMA 2020 and registered in PROSPERO (CRD420261288376). Randomized controlled trials and observational studies reporting female-specific LDL-C outcomes following treatment with PCSK9 monoclonal antibodies (evolocumab and alirocumab) were included. The primary outcome was percentage change in LDL-C from baseline. Risk of bias was assessed using the Newcastle–Ottawa Scale for observational studies. Results Three observational cohort studies (n = 353 female participants total) were included in the quantitative synthesis. Variance data could not be derived for the remaining observational studies. The pooled mean percentage reduction in LDL-C at 12–30 weeks was −48.4% (95% CI −62.7% to −34.1%; P = 0.005), with high heterogeneity (I2 = 73%). Narrative synthesis of randomized trial subgroup analyses demonstrated LDL-C reductions ranging from approximately −45% to −60%. Conclusions This review synthesized available female-specific LDL-C evidence for PCSK9 monoclonal antibodies. Available evidence suggests substantial LDL-C reductions among female patients; however, these findings are based on a limited quantitative evidence base consisting of three observational cohort studies and should be interpreted cautiously. Interpretation is limited to LDL-C outcomes, which represent a surrogate marker rather than a direct clinical outcome, as cardiovascular outcomes and ASCVD event reduction were not evaluated in this review.