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.

Abstract

<h4>Introduction</h4>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 <i>versus</i> placebo in the general population and solid organ transplant (SOT) recipients.<h4>Materials and methods</h4>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 <i>RevMan5.3</i> and <i>Stata20.0</i>. The cumulative ranking probability curve (SUCRA) compared impact of different treatment regimens (DTRs) on patient efficacy, safety, and ACM.<h4>Results</h4>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).<h4>Conclusion</h4>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.