What question did this study set out to answer?

To assess how CYP2C19 genotype variants affect the efficacy of lipid-lowering therapies in sICAS patients.

December 23, 2025Lipids0 citationsOpen Access

Impact of CYP2C19 Genotype Variants on PCSK9 Inhibitor Efficacy in Lipid‐Lowering Among Patients With Symptomatic Intracranial Atherosclerotic Stenosis

CZChao ZhaoUniversity of Alabama NWNuan WangXuzhou Medical College DSDi ShiBeijing Institute of Technology

Key Points

To assess how CYP2C19 genotype variants affect the efficacy of lipid-lowering therapies in sICAS patients.
Clinical trial with 151 patients divided into statin and PCSK9 inhibitor groups.
Evaluation of lipid profiles, inflammatory markers, and neurological function over 180 days.
Comparison of treatment effects between rapid and slow metabolizers of the CYP2C19 gene.
PCSK9i group showed significant reductions in LDL-C, total cholesterol, and triacylglycerols compared to the statin group.
Inflammatory marker IL-6 significantly reduced in the PCSK9i group.
Rapid metabolizers had significantly greater reductions in LDL-C and ApoB compared to slow metabolizers.

Abstract

ABSTRACT Ischemic stroke is frequently associated with symptomatic intracranial atherosclerotic stenosis (sICAS), is a leading cause of global disability and mortality. Current guidelines recommend dual antiplatelet and intensive statin therapies. Proprotein convertase subtilisin 9/kexin type 9 (PCSK9) inhibitors have emerged as a potent lipid‐lowering therapy, potentially influenced by genetic variations, particularly in the CYP2C19 gene. This study at Xuzhou Central Hospital from January 2021 to December 2023 included 151 patients divided into a statin group ( n = 73) and a PCSK9 inhibitor (PCSK9i) group ( n = 78). It evaluated lipid profiles, inflammatory markers, neurological function, and clinical outcomes over a 180‐day follow‐up period, with additional analysis stratified by CYP2C19 genotype. The PCSK9i group demonstrated significant improvements in lipid parameters compared to the statin group, including greater reductions in low‐density lipoprotein cholesterol (LDL‐C) ( p = 0.008), total cholesterol (TC) ( p < 0.001), and triacylglycerols (TAG) ( p = 0.041), along with apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) (both p < 0.001). Inflammatory markers, particularly interleukin‐6 (IL‐6), significantly reduced in the PCSK9i group ( p < 0.001). In the PCSK9i group, CYP2C19 rapid metabolizers achieved greater reductions in LDL‐C ( p = 0.021), ApoB ( p = 0.003), and IL‐6 levels ( p = 0.041) compared to slow metabolizers. Post‐treatment modified Rankin Scale (mRS) scores were significantly lower in rapid metabolizers compared to slow metabolizers ( p = 0.018), though clinical events occurred infrequently in both subgroups. This study demonstrates that PCSK9 inhibitor therapy combined with statins provides enhanced lipid‐lowering and anti‐inflammatory effects compared to statin monotherapy in sICAS patients. While the CYP2C19 genotype may influence specific treatment responses, particularly lipid parameters, its impact on clinical outcomes requires further investigation.

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