Alaíz Álvaro Rodrigo, Gudino Luis Corral, de la Isla Leopoldo Pérez, Pardo Héctor García, Calle David González, Miramontes-González José Pablo
School of Medicine, Valladolid University, 47003 Valladolid, Spain.
Internal Medicine Unit, Río Hortega University Hospital, 47003 Valladolid, Spain.
J Clin Med. 2025 Jun 12;14(12):4163. doi: 10.3390/jcm14124163.
Inclisiran is a novel lipid-lowering agent targeting PCSK9 via small interfering RNA (siRNA) technology. While clinical trials such as the ORION studies have demonstrated significant reductions in low-density lipoprotein cholesterol (c-LDL), real-world data (RWD) often differ due to variations in patient populations and clinical practices. This systematic review and meta-analysis adhered to PRISMA guidelines. A comprehensive search was conducted in MEDLINE for real-world studies evaluating inclisiran's efficacy in reducing c-LDL. Articles meeting predefined inclusion criteria were assessed for quality and bias using RTI Item Bank. Data transformations were applied to harmonize median and IQR values to means and standard deviations for meta-analytic synthesis using RevMan 5.4. A total of 3774 articles were identified, of which 7 studies comprising 1454 patients met the inclusion criteria. The meta-analysis revealed an average c-LDL reduction of 42.77% (95% CI: 37.42-48.12%). The subgroup analysis indicated greater reductions in patients receiving inclisiran alongside statins (45.67%; 95% CI: 36.64-54.71%) compared to monotherapy (37.53%; 95% CI: 29.91-45.15%). Discrepancies with clinical trials (e.g., 52% reduction in ORION studies) were attributed to baseline c-LDL differences and real-world adherence. Inclisiran demonstrates robust efficacy in real-world settings, achieving significant c-LDL reductions with a convenient dosing schedule. However, the observed discrepancies with clinical trials highlight the need for further RWD studies to bridge gaps in effectiveness and optimize therapeutic outcomes.
英克西兰是一种通过小干扰RNA（siRNA）技术靶向前蛋白转化酶枯草溶菌素9（PCSK9）的新型降脂药物。虽然诸如ORION研究等临床试验已证明低密度脂蛋白胆固醇（c-LDL）显著降低，但由于患者群体和临床实践的差异，真实世界数据（RWD）往往有所不同。本系统评价和荟萃分析遵循PRISMA指南。在MEDLINE中进行了全面检索，以查找评估英克西兰降低c-LDL疗效的真实世界研究。使用RTI项目库对符合预定义纳入标准的文章进行质量和偏倚评估。应用数据转换将中位数和四分位间距值统一为均值和标准差，以便使用RevMan 5.4进行荟萃分析合成。共识别出3774篇文章，其中7项研究（包括1454名患者）符合纳入标准。荟萃分析显示，c-LDL平均降低42.77%（95%CI：37.42-48.12%）。亚组分析表明，与单药治疗（37.53%；95%CI：29.91-45.15%）相比，接受英克西兰联合他汀类药物治疗的患者c-LDL降低幅度更大（45.67%；95%CI：36.64-54.71%）。与临床试验的差异（例如，ORION研究中降低52%）归因于基线c-LDL差异和真实世界中的依从性。英克西兰在真实世界环境中显示出强大的疗效，通过便捷的给药方案实现了c-LDL的显著降低。然而，观察到的与临床试验的差异凸显了进一步开展真实世界数据研究以弥合有效性差距并优化治疗结果的必要性。
