Elvan Wiyarta, Rakhmad Hidayat, Mohammad Kurniawan, Bryanna Infinita Laviashna Saputro, Indira Laksmi Maharani, Derren David Christian Homenta Rampengan, Lucia Callista Tanudharma, Raymond Rubianto Tjandrawinata
{"title":"Therapeutic Potential of Lumbrokinase in Acute Ischemic Stroke: A Meta-Analysis of Efficacy and Safety.","authors":"Elvan Wiyarta, Rakhmad Hidayat, Mohammad Kurniawan, Bryanna Infinita Laviashna Saputro, Indira Laksmi Maharani, Derren David Christian Homenta Rampengan, Lucia Callista Tanudharma, Raymond Rubianto Tjandrawinata","doi":"10.2147/TCRM.S537232","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>Lumbrokinase may safely improve stroke outcomes; however, limited evidence warrants cautious use and further high-quality trials.</p>","PeriodicalId":22977,"journal":{"name":"Therapeutics and Clinical Risk Management","volume":"21 ","pages":"1319-1331"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417717/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutics and Clinical Risk Management","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/TCRM.S537232","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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.
Methods: 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.
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).
Conclusion: Lumbrokinase may safely improve stroke outcomes; however, limited evidence warrants cautious use and further high-quality trials.
期刊介绍:
Therapeutics and Clinical Risk Management is an international, peer-reviewed journal of clinical therapeutics and risk management, focusing on concise rapid reporting of clinical studies in all therapeutic areas, outcomes, safety, and programs for the effective, safe, and sustained use of medicines, therapeutic and surgical interventions in all clinical areas.
The journal welcomes submissions covering original research, clinical and epidemiological studies, reviews, guidelines, expert opinion and commentary. The journal will consider case reports but only if they make a valuable and original contribution to the literature.
As of 18th March 2019, Therapeutics and Clinical Risk Management will no longer consider meta-analyses for publication.
The journal does not accept study protocols, animal-based or cell line-based studies.