Li Wangwen, Wu Chuyue, Li Wenkui, Li Li
Department of Neurology, Chongqing University Three Gorges Hospital, Wanzhou, Chongqing 400016, China; School of Medicine, Chongqing University, Chongqing 404010, China.
Department of Neurology, Chongqing University Three Gorges Hospital, Wanzhou, Chongqing 400016, China; School of Medicine, Chongqing University, Chongqing 404010, China; Chongqing Municipality Clinical Research Center for Geriatric diseases, Chongqing University Three Gorges Hospital, Wanzhou, Chongqing 400016, China.
J Stroke Cerebrovasc Dis. 2025 Feb;34(2):108224. doi: 10.1016/j.jstrokecerebrovasdis.2025.108224. Epub 2025 Jan 2.
Statin therapy reduces the risk of ischemic stroke; however, certain studies have observed an increased incidence of intracerebral hemorrhage (ICH). Moreover, proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors have emerged as a powerful class of lipid-lowering medications, potentially with a lower propensity for causing hemorrhagic events. To investigate this matter further, we conducted a network meta-analysis of randomized controlled trials (RCTs) involving statins and PCSK-9 inhibitors that reported occurrences of ICH.
We performed a literature search of Medline, Web of Science, and The Cochrane Library from database inception until August 2023. All randomized controlled trials of statin therapy and PCSK-9 inhibitors that reported ICH or hemorrhagic stroke were included. The primary outcome variable was ICH. The risk of bias of each included study was assessed by using the Cochrane Handbook for Systematic Reviews of Interventions. We performed network meta-analysis to compare and rank statin and PCSK-9 inhibitors therapies. This study is registered (2023110026. inplasy.com).
A total of 26251 citations were identified by the search, and 38 potentially eligible articles were included. In total, data from 271411 individuals were analyzed. The data showed that there was not a significant increased risk of intracerebral hemorrhage for all statins and PCSK-9 inhibitors compared with placebo. atorvastatin and rosuvastatin were associated with a lower risk of death than placebo (ORs ranging between 0.79 and 0.82). For risk of intracerebral hemorrhage and mortality. there was not a significant increased risk among all drugs.
LDL-Cholesterol lowering agents (statins and PCSK-9 inhibitors) was not associated with a significant increased risk of ICH. Our network meta-analysis provides strong evidence for the safety of statins and PCSK-9 inhibitors, but more studies are needed to further validate this conclusion.
他汀类药物治疗可降低缺血性卒中风险；然而，某些研究观察到脑出血（ICH）发病率增加。此外，前蛋白转化酶枯草溶菌素9型（PCSK - 9）抑制剂已成为一类强效降脂药物，可能引起出血事件的倾向较低。为进一步研究此事，我们对报告了ICH发生情况的他汀类药物和PCSK - 9抑制剂的随机对照试验（RCT）进行了网状Meta分析。
我们对Medline、科学网和考克兰图书馆进行了从数据库建立至2023年8月的文献检索。纳入所有报告了ICH或出血性卒中的他汀类药物治疗和PCSK - 9抑制剂的随机对照试验。主要结局变量为ICH。使用《考克兰系统评价干预措施手册》评估每项纳入研究的偏倚风险。我们进行网状Meta分析以比较和排序他汀类药物和PCSK - 9抑制剂治疗。本研究已注册（2023110026. inplasy.com）。
检索共识别出26251条引文，纳入38篇潜在符合条件的文章。总共分析了来自271411名个体的数据。数据显示，与安慰剂相比，所有他汀类药物和PCSK - 9抑制剂的脑出血风险均未显著增加。阿托伐他汀和瑞舒伐他汀与比安慰剂更低的死亡风险相关（比值比范围在0.79至0.82之间）。对于脑出血风险和死亡率，所有药物之间均未观察到显著增加风险。
降低低密度脂蛋白胆固醇的药物（他汀类药物和PCSK - 9抑制剂）与ICH风险显著增加无关。我们的网状Meta分析为他汀类药物和PCSK - 9抑制剂的安全性提供了有力证据，但需要更多研究来进一步验证这一结论。
