The Efficacy and Safety of Four Novel PCSK9 Monoclonal Antibodies in Patients With Hypercholesterolemia: A Systematic Review With Network Meta‐Analysis and Trial Sequential Analysis

Aim This network meta‐analysis (NMA) evaluated four novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies for hypercholesterolemia management, comparing their lipid‐lowering efficacy and safety. Methods We systematically identified randomized controlled trials employing the frequentist NMA method to assess reductions in low‐density lipoprotein cholesterol (LDL‐C), apolipoprotein B (ApoB), and lipoprotein (a) (Lp[a]), alongside treatment‐emergent adverse events (TEAEs) and serious TEAEs. P ‐scores ranked therapeutic hierarchies, with meta‐regression and subgroup analyses exploring heterogeneity. Trial sequential analysis determined the adequacy of cumulative evidence. Confidence in the network meta‐analysis approach was used to evaluate the confidence in the findings from NMA. Results A total of eight trials with 3,975 Chinese patients were included. Ongericimab 150 mg every 2 weeks (Q2W) ranked first in all efficacy outcomes, demonstrating pronounced effects in LDL‐C, ApoB, and Lp(a) reduction versus placebo, with mean differences of −74.21% (95% confidence interval [CI]: −79.69% to −68.73%), −64.36% (95% CI: −68.58% to −60.13%), and −50.93% (95% CI: −56.24% to −45.61%), respectively. All interventions exhibited safety profiles comparable with placebo, with no significant differences in TEAEs or serious TEAEs incidence. The analyses suggested that a portion of the evidence base was robust and reliable. Conclusion These findings positioned ongericimab 150 mg Q2W as a clinically optimal PCSK9 inhibitor with robust lipid‐lowering capacity. The results highlight the potential of next‐generation PCSK9 monoclonal antibodies, particularly in East Asian populations, while underscoring the need for large‐scale multinational trials to validate ethnic‐specific responses.