Effect of large artery atherosclerosis subtype on the efficacy of Ginkgo Diterpene Lactone Meglumine in acute ischemic stroke

doi:10.3969/j.issn.1006-7795.2025.02.008

Abstract

Abstract: Objective To investigate the effect of large artery atherosclerosis (LAA) and non-LAA subtypes on the efficacy of Ginkgo Diterpene Lactone Meglumine (GDLM) in patients with acute ischemic stroke. Methods This was a post-hoc analysis of multicenter, randomized, double-blind, placebo-controlled, and parallel-group trial. A total of 3 448 patients who had acute ischemic stroke were randomly assigned in a 1∶1 ratio to receive the injection of GDLM or the placebo once day within 48 h after symptoms and continued for 14 d. The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) of 0 or 1 on day 90 after randomization. Results A total of 3 448 patients were enrolled, with 1 604 (46.52%) patients with non-LAA and 1 844 (53.48%) with LAA. Compared to the placebo treatment. GDLM injection effectively improve the functional prognosis, with a higher proportion of mRS score of 0-1 in both non-LAA (OR=1.24, 95% CI: 1.02-1.51; P=0.03) and LAA (OR=1.37, 95% CI:1.14-1.65; P<0.001) group. There was no significant interaction between LAA subtypes with treatment (P=0.48 for interaction). Conclusion Among patients with acute ischemic stroke in this randomized clinical trial, GDLM might improve the favorable clinical outcomes at 90 d compared with placebo, regardless of LAA subtypes. Nevertheless, it is necessary to confirm the findings in the future.

Key words: large artery atherosclerosis subtypes, Ginkgo Diterpene Lactone Meglumine injection, ischemic stroke, functional outcome, randomized clinical trial

CLC Number:

R742

Jing Jiao, Zhang Siyao, Liu Yanling, Wang Fen, Xiao Wei, Wang Zhenzhong. Effect of large artery atherosclerosis subtype on the efficacy of Ginkgo Diterpene Lactone Meglumine in acute ischemic stroke[J]. Journal of Capital Medical University, 2025, 46(2): 228-233.

References

［1］GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990－2019: a systematic analysis for the Global Burden of Disease Study 2019［J］. Lancet Neurol, 2021, 20(10): 795－820.
［2］Benjamin E J, Blaha M J, Chiuve S E, et al. Heart disease and stroke statistics－2017 update: a report from the American heart association［J］. Circulation, 2017, 135(10): e146-e603.
［3］Chamorro Á, Dirnagl U, Urra X, et al. Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation［J］. Lancet Neurol, 2016, 15(8): 869－881.
［4］Saver J L, Starkman S, Eckstein M, et al. Prehospital use of magnesium sulfate as neuroprotection in acute stroke［J］. N Engl J Med, 2015, 372(6): 528－536.
［5］Shuaib A, Lees K R, Lyden P, et al. NXY-059 for the treatment of acute ischemic stroke［J］. N Engl J Med, 2007, 357(6): 562－571.
［6］Elkins J, Veltkamp R, Montaner J, et al. Safety and efficacy of natalizumab in patients with acute ischaemic stroke (ACTION): a randomised, placebo-controlled, double-blind phase 2 trial［J］. Lancet Neurol, 2017, 16(3): 217－226.
［7］Wang T J, Wu Z Y, Yang C H, et al. Multiple mechanistic models reveal the neuroprotective effects of diterpene ginkgolides against astrocyte-mediated demyelination via the PAF-PAFR pathway［J］. Am J Chin Med, 2022, 50(6): 1565－1597.
［8］Fan X X, Cao Z Y, Liu M X, et al. Diterpene ginkgolides meglumine injection inhibits apoptosis induced by optic nerve crush injury via modulating MAPKs signaling pathways in retinal ganglion cells［J］. J Ethnopharmacol, 2021, 279: 114371.
［9］Zhang W, Song J K, Yan R, et al. Diterpene ginkgolides protect against cerebral ischemia/reperfusion damage in rats by activating Nrf2 and CREB through PI3K/Akt signaling［J］. Acta Pharmacol Sin, 2018, 39(8): 1259－1272.
［10］Zhao S, Zheng H, Du Y W, et al. The clinical efficacy of Ginkgo biloba leaf preparation on ischemic stroke: a systematic review and Meta-analysis［J］. Evid Based Complement Alternat Med, 2021, 2021: 4265219.
［11］Zhao H, Guo Q, Li B L, et al. The efficacy and safety of ginkgo terpene lactone preparations in the treatment of ischemic stroke: a systematic review and Meta-analysis of randomized clinical trials［J］. Front Pharmacol, 2022, 13: 821937.
［12］Zhang Q, Wang A X, Xu Q, et al. Efficacy and safety of ginkgo diterpene lactone meglumine in acute ischemic stroke: a randomized clinical trial［J］. JAMA Netw Open, 2023, 6(8): e2328828.
［13］中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性缺血性脑卒中诊治指南2014［J］. 中华神经科杂志, 2015, 48(4)： 246－257.
［14］Adams H P, Bendixen B H, Kappelle L J, et al . Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial［J］. Stroke, 1993, 24: 35－41.
［15］黄志鑫, 李东航, 王喜江, 等. 银杏二萜内酯联合双抗治疗轻型缺血性脑卒中的近远期效果［J］. 中国医学创新, 2020, 17(6): 1－5.
［16］姜丹, 马连星. 银杏叶提取物结合早期康复治疗对缺血性脑卒中的疗效观察［J］. 中国临床保健杂志, 2006, 9(6): 580－582.
［17］Shin D I, Lee H S, Baek S H, et al. Noninvasive qureshi grading scheme predicts 90-day mRS in patients with acute ischemic stroke［J］. J Neuroimaging, 2015, 25(5): 761－765.
［18］顾香, 邢铁艳. 银杏叶提取物注射液治疗急性脑梗死的临床效果观察［J］. 中医药导报, 2015, 21(2): 70－72.
［19］李光硕, 赵性泉. 《中国急性缺血性卒中诊治指南2023》解读［J］. 中国卒中杂志, 2024, 19(8): 956－961.
［20］杨普香, 胡炜娜, 余陈欣, 等. 银杏叶提取物联合高压氧、甲磺酸倍他司汀治疗眩晕症的疗效观察［J］. 新疆医科大学学报, 2024, 47(11): 1470－1475.
［21］杜雪峰, 张国辉, 陈晓丽, 等. 银杏叶提取物联合尼莫地平治疗血管性眩晕患者的临床效果及对椎基底动脉血流量的影响［J］. 临床误诊误治, 2021, 34(3): 41－45.
［22］北京脑血管病防治协会银杏叶提取物注射液临床应用专家共识写作组. 银杏叶提取物注射液临床应用中国专家共识(2019)［J］. 中华老年医学杂志, 2019, 38(11): 1198－1204.
［23］张旭, 陈旺盛, 冯健, 等. 银杏内酯B保护缺氧/复氧诱导心肌细胞损伤模型的作用及机制［J］. 中国组织工程研究, 2019, 23(19): 3097－3101.
［24］苏东风, 李岩松, 潘浩圃. 银杏二萜内酯葡胺治疗急性缺血性脑卒中疗效观察［J］. 临床军医杂志, 2018, 46(8): 932－934.
［25］潘亮发, 邱小山, 曾瑛. 银杏二萜内酯葡胺注射液治疗脑梗死恢复期的临床疗效及其对患者血液流变学的影响［J］. 临床合理用药杂志, 2022, 15(27): 12－14, 19.
［26］吕刚. 银杏二萜内酯葡胺注射液在急性脑梗死患者疗效及神经功能的影响研究［J］. 临床医药文献电子杂志, 2019, 6(52): 170－171.

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