Wiyarta Elvan, Hidayat Rakhmad, Kurniawan Mohammad, Saputro Bryanna Infinita Laviashna, Maharani Indira Laksmi, Rampengan Derren David Christian Homenta, Tanudharma Lucia Callista, Tjandrawinata Raymond Rubianto
Intensive Care Department, University of Indonesia Hospital, Depok, 16424, Indonesia.
Department of Neurology, University of Indonesia, Cipto Mangunkusumo National Referral Hospital, Jakarta, 10430, Indonesia.
Ther Clin Risk Manag. 2025 Sep 4;21:1319-1331. doi: 10.2147/TCRM.S537232. eCollection 2025.
Acute ischemic stroke (AIS) requires rapid treatment. Although alteplase is a standard thrombolytic therapy, its limited availability in low-resource settings presents a challenge. Lumbrokinase, a fibrinolytic enzyme isolated from earthworms, has been proposed as an adjunct treatment option. This meta-analysis evaluated efficacy and safety in addition to supportive care.
A systematic review of randomized controlled trials (RCTs) was conducted using multiple databases through July 2024 following PRISMA guidelines. The risk of bias was assessed using RoB 2.0, and evidence quality was graded using GRADE. Publication bias was evaluated using funnel plots. Meta-analyses employed a random-effects model and reported odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals. Primary outcomes included the Barthel Index and NIHSS scores, and secondary outcomes included adverse events and laboratory results.
A total of 35 RCTs published between 2010 and 2024 were included. Compared with supportive care alone, lumbrokinase adjunct therapy significantly improved Barthel Index scores (MD = 15.17; 95% CI: 14.60 to 15.74) and reduced NIHSS scores (MD = -2.01; 95% CI: -2.06 to -1.97). Safety analyses revealed no significant increase in adverse events including gastrointestinal discomfort (OR = 1.00; 95% CI: 0.32 to 3.16) and GI bleeding (OR = 1.42; 95% CI: 0.55 to 3.67). Laboratory assessments indicated improvements in aPTT (MD = 1.93; 95% CI: 1.58 to 2.28), platelet aggregation rate (MD = -205.86; 95% CI, -206.77 to -204.96), and D-dimer levels (MD = -0.04; 95% CI: -0.05 to -0.03).
Lumbrokinase may safely improve stroke outcomes; however, limited evidence warrants cautious use and further high-quality trials.
急性缺血性卒中（AIS）需要快速治疗。尽管阿替普酶是标准的溶栓疗法，但在资源匮乏地区其可用性有限，这构成了一项挑战。蚓激酶是一种从蚯蚓中分离出的纤溶酶，已被提议作为辅助治疗选择。本荟萃分析除评估了支持性治疗外，还评估了其疗效和安全性。
按照PRISMA指南，通过多个数据库对截至2024年7月的随机对照试验（RCT）进行了系统评价。使用RoB 2.0评估偏倚风险，并使用GRADE对证据质量进行分级。使用漏斗图评估发表偏倚。荟萃分析采用随机效应模型，并报告了优势比（OR）和平均差（MD）以及95%置信区间。主要结局包括巴氏指数和美国国立卫生研究院卒中量表（NIHSS）评分，次要结局包括不良事件和实验室检查结果。
纳入了2010年至2024年发表的共35项RCT。与单纯支持性治疗相比，蚓激酶辅助治疗显著提高了巴氏指数评分（MD = 15.17；95% CI：14.60至15.74），并降低了NIHSS评分（MD = -2.01；95% CI：-2.06至-1.97）。安全性分析显示，包括胃肠道不适（OR = 1.00；95% CI：0.32至3.16）和消化道出血（OR = 1.42；95% CI：0.55至3.67）在内的不良事件没有显著增加。实验室评估表明，活化部分凝血活酶时间（aPTT）（MD = 1.93；95% CI：1.58至2.28）、血小板聚集率（MD = -205.86；95% CI：-206.77至-204.96）和D-二聚体水平（MD = -0.04；95% CI：-0.05至-0.03）有所改善。
蚓激酶可能安全地改善卒中结局；然而，证据有限，需谨慎使用并开展进一步的高质量试验。
