LDL-cholesterol lowering agents (statins and PCSK9 inhibitors) and the risk of intracerebral hemorrhage: A network meta-analysis

Wangwen Li; Chuyue Wu; Wenkui Li; Li Li

doi:10.1016/j.jstrokecerebrovasdis.2025.108224

LDL-cholesterol lowering agents (statins and PCSK9 inhibitors) and the risk of intracerebral hemorrhage: A network meta-analysis

J Stroke Cerebrovasc Dis. 2025 Jan 2;34(2):108224. doi: 10.1016/j.jstrokecerebrovasdis.2025.108224. Online ahead of print.

Authors

Wangwen Li¹, Chuyue Wu², Wenkui Li³, Li Li⁴

Affiliations

¹ Department of Neurology, Chongqing University Three Gorges Hospital, Wanzhou, Chongqing 400016, China; School of Medicine, Chongqing University, Chongqing 404010, China. Electronic address: [email protected].
² 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. Electronic address: [email protected].
³ Department of Neurology, Chongqing University Three Gorges Hospital, Wanzhou, Chongqing 400016, China; School of Medicine, Chongqing University, Chongqing 404010, China. Electronic address: [email protected].
⁴ Department of Neurology, Chongqing University Three Gorges Hospital, Wanzhou, Chongqing 400016, China; School of Medicine, Chongqing University, Chongqing 404010, China. Electronic address: [email protected].

PMID: 39755190
DOI: 10.1016/j.jstrokecerebrovasdis.2025.108224

Abstract

Background and purpose: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Keywords: Intracerebral hemorrhage; Network meta-analysis; Randomized controlled trials; Statin therapy.