前蛋白转化酶枯草溶菌素9型（PCSK9）抑制剂联合他汀类药物治疗高胆固醇血症患者的疗效和安全性：一项网状Meta分析。
The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors combined with statins in patients with hypercholesterolemia: a network meta-analysis.
作者信息
Liu Dong, Zhang Jin, Zhang Xiaoyu, Jiang Fengli, Wu Yiping, Yang Beibei, Li Xinghuan, Fan Xiongxiong, Li Han, Sun Yu, Gou Ruijie, Wang Xinyu
机构信息
Clinical Pharmacy Office, Baoji Central Hospital, Baoji, Shaanxi, China.
出版信息
Front Cardiovasc Med. 2024 Sep 25;11:1454918. doi: 10.3389/fcvm.2024.1454918. eCollection 2024.
BACKGROUND
In recent years, the position of PCSK9 inhibitors as adjuvant therapy to statins in guidelines has further improved. However, there remained a dearth of direct comparative studies among different PCSK9 inhibitors. Therefore, this study aimed to conduct a network meta-analysis to evaluate the efficacy and safety of different PCSK9 inhibitors combined with statins.
METHODS
A comprehensive literature search was conducted from the study's inception to 12 November 2023, encompassing multiple online databases including PubMed, Embase, Cochrane Central, Web of Science, and ClinicalTrials.gov to obtain relevant randomized controlled trials. Frequentist network meta-analysis was employed to compare the efficacy and safety of different PCSK9 inhibitors. The efficacy endpoints were low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) (Lp(a)). The safety endpoints were any adverse events (AE), severe adverse events (SAE), AE leading to treatment discontinuation, and injection-site reaction.
RESULTS
Compared with placebo and ezetimibe, all PCSK9 inhibitors demonstrated significant reductions in LDL-C levels. Notably, evolocumab exhibited the most pronounced effect with a treatment difference of -63.67% (-68.47% to -58.87%) compared with placebo. Regarding dosage selection for evolocumab, the regimen of 140 mg Q2W (-69.13%, -74.55% to -63.72%) was superior to 420 mg QM (-61.51%, -65.97% to -57.05%). Based on rankings and -scores analysis, tafolecimab 150 mg Q2W demonstrated superior efficacy in reducing ApoB levels (-61.70%, -84.38% to -39.02%) and Lp(a) levels (-43%, 30%, -68%, 81% to -17%, 79%). Furthermore, the safety profile of PCSK9 inhibitors was favorable with no increase in the incidence of AE, SAE, or AE leading to treatment discontinuation; however, alirocumab, inclisiran, and tafolecimab may potentially entail a potential risk associated with injection-site reactions.
CONCLUSION
Compared with placebo and ezetimibe, PCSK9 inhibitors can significantly reduce LDL-C, ApoB, and Lp(a) when combined with statins to treat hypercholesterolemia. Furthermore, PCSK9 inhibitors and ezetimibe exhibit similar safety profiles.
SYSTEMATIC REVIEW REGISTRATION
[PROSPERO], identifier [CRD42023490506].
背景
近年来，前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂在指南中作为他汀类药物辅助治疗的地位进一步提升。然而，不同PCSK9抑制剂之间仍缺乏直接比较研究。因此，本研究旨在进行一项网状Meta分析，以评估不同PCSK9抑制剂与他汀类药物联合使用的疗效和安全性。
方法
从研究开始至2023年11月12日进行了全面的文献检索，涵盖多个在线数据库，包括PubMed、Embase、Cochrane Central、Web of Science和ClinicalTrials.gov，以获取相关的随机对照试验。采用频率学派网状Meta分析来比较不同PCSK9抑制剂的疗效和安全性。疗效终点为低密度脂蛋白胆固醇（LDL-C）、载脂蛋白B（ApoB）和脂蛋白（a）[Lp（a）]。安全性终点为任何不良事件（AE）、严重不良事件（SAE）、导致治疗中断的AE和注射部位反应。
结果
与安慰剂和依折麦布相比，所有PCSK9抑制剂均显示LDL-C水平显著降低。值得注意的是，与安慰剂相比，阿利西尤单抗的效果最为显著，治疗差异为-63.67%（-68.47%至-58.87%）。关于阿利西尤单抗的剂量选择，每2周一次140mg的方案（-69.13%，-74.55%至-63.72%）优于每月一次420mg的方案（-61.51%，-65.97%至-57.05%）。基于排名和 -评分分析，每2周一次150mg的替伏西单抗在降低ApoB水平（-61.70%，-84.38%至-39.02%）和Lp（a）水平（-43%，30%，-68%，81%至-17%，79%）方面显示出更优的疗效。此外，PCSK9抑制剂的安全性良好，AE、SAE或导致治疗中断的AE发生率均未增加；然而，阿利西尤单抗、inclisiran和替伏西单抗可能存在与注射部位反应相关的潜在风险。
结论
与安慰剂和依折麦布相比，PCSK9抑制剂与他汀类药物联合治疗高胆固醇血症时可显著降低LDL-C、ApoB和Lp（a）。此外，PCSK9抑制剂和依折麦布的安全性相似。
系统评价注册
[PROSPERO]，标识符[CRD42023490506]
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