Work

Efficacy and safety of different proprotein convertase subtilisin/kexin type 9 inhibitors in the general population and solid organ transplant recipients: a network meta-analysis

Year: 2025

Type: article

Study designs: Systematic Review, Meta-Analysis

Abstract: Introduction We conducted a network meta-analysis (NMA) to compare the efficacy (primarily assessed by low-density lipoprotein cholesterol (LDL-C) reduction and cardiovascular event (CVE) incidence) and safety (total adverse events (AEs), neurocognitive events (NCEs), injection site reactions, infections, and all-cause mortality (ACM)) of different Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors versus placebo in the general population and solid organ transplant (SOT) recipients. Materials and Methods A total of 16 randomized controlled trials (RCTs) involving 79,615 patients were included. Cochrane risk of bias assessment tool evaluated the literature quality. Data analysis and graph generation were conducted employing RevMan5.3 and Stata20.0. The cumulative ranking probability curve (SUCRA) compared impact of different treatment regimens (DTRs) on patient efficacy, safety, and ACM. Results Evolocumab ranked highest for LDL-C reduction (SUCRA 67.2%) and CVE reduction (SUCRA 69.5%). Ongericimab had the lowest total AEs (SUCRA 91.3%), while Alirocumab ranked best for NCEs (SUCRA 89.5%) and infections (SUCRA 74.1%). Placebo had the fewest injection site reactions (SUCRA 89.8%). No PCSK9 inhibitor significantly reduced ACM (Alirocumab SUCRA 69.0%, highest but non-significant). LDL-C reduction was significant in both general and SOT populations, but CVE and ACM reductions were non-significant. Inclisiran increased risks of total AEs and injection site reactions (RR > 1.2). Conclusion Evolocumab is optimal for LDL-C and CVE reduction, while Ongericimab and Alirocumab offer better safety profiles. PCSK9 inhibitors did not increase acute rejection or infection risk in SOT recipients. Long-term mortality benefits remain uncertain.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2025.1584612

Authors: Bohan Luo, Zhuang Sun, Han Luo

Institutions: University of Electronic Science and Technology of China, Chinese Academy of Sciences, Ningbo Institute of Industrial Technology

Language: English

Topic: Lipoproteins and Cardiovascular Health

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801