{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T11:47:35Z","timestamp":1770292055844,"version":"3.49.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Quzhou City Science and Technology Research Project in 2023","award":["2023k193"],"award-info":[{"award-number":["2023k193"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The effectiveness of administering argatroban as a treatment approach following antiplatelet therapy or alteplase thrombolytic therapy in patients with acute stroke is presently uncertain. However, it is important to highlight the potential benefits of combining this medication with known thrombolytics or antiplatelet therapy. One notable advantage of argatroban is its short half-life, which helps minimize excessive anticoagulation and risk of bleeding complications in inadvertent cases of hemorrhagic stroke. By conducting a meticulous review and meta-analysis, we aim to further explore the common use of argatroban and examine the plausible advantages of combining this medication with established thrombolytic and antiplatelet therapies.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Method<\/jats:title>\n<jats:p>In this study, we performed a rigorous and methodical search for both randomized controlled trials and retrospective analyses. Our main objective was to analyze the impact of argatroban on the occurrence of hemorrhagic events and the mRS scores of 0\u20132. We utilized a meta-analysis to assess the relative risk (RR) associated with using argatroban versus not using it.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>In this study, we analyzed data from 11 different studies, encompassing a total of 8,635 patients. Out of these patients, 3999(46.3%) received argatroban treatment while the remaining 4636(53.7%)did not. The primary outcome of 90-day functional independence (modified Rankin scale (mRS) score\u22642) showed that the risk ratio (RR) for patients using argatroban after alteplase thrombolytic therapy compared to those not using argatroban was(RR, 1.00 ([95% CI, 0.92\u20131.09]; P = 0.97), indicating no statistical significance. However, for patients using argatroban after antiplatelet therapy, was (RR,1.09 [95% CI, 1.04\u20131.14]; P = 0.0001), which was statistically significant. In terms of hemorrhagic events, the RR for patients using argatroban compared to those not using argatroban was (RR,1.08 [95% CI, 0.88\u20131.33]; P = 0.46), indicating no statistical significance.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The results of this study suggest that further research into combination therapy with argatroban and antiplatelet agents may be warranted, however more rigorous RCTs are needed to definitively evaluate the effects of combination treatment.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0298226","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T18:27:43Z","timestamp":1709058463000},"page":"e0298226","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Can the combination of antiplatelet or alteplase thrombolytic therapy with argatroban benefit patients suffering from acute stroke? a systematic review, meta-analysis, and meta-regression"],"prefix":"10.1371","volume":"19","author":[{"given":"Haiyan","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wukun","family":"Ge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4493-8792","authenticated-orcid":true,"given":"Xiuping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengjiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyong","family":"Lan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yina","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"issue":"10","key":"pone.0298226.ref001","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional, and national burden of stroke and its risk factors, 1990\u20132019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"20","year":"2021","journal-title":"Lancet Neurol"},{"issue":"25","key":"pone.0298226.ref002","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1056\/NEJMoa1804492","article-title":"Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016","volume":"379","author":"VL Feigin","year":"2018","journal-title":"New Engl J Med"},{"issue":"1","key":"pone.0298226.ref003","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S1474-4422(16)30283-6","article-title":"Stroke 1-2-0: a rapid response programme for stroke in China.","volume":"16","author":"J Zhao","year":"2017","journal-title":"Lancet Neurol."},{"issue":"1","key":"pone.0298226.ref004","doi-asserted-by":"crossref","first-page":"I","DOI":"10.1177\/2396987321989865","article-title":"European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke.","volume":"6","author":"E Berge","year":"2021","journal-title":"Eur Stroke J."},{"issue":"3","key":"pone.0298226.ref005","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1056\/NEJMe2018927","article-title":"Antiplatelet Treatment to Prevent Early Recurrent Stroke","volume":"383","author":"PM Rothwell","year":"2020","journal-title":"New Engl J Med"},{"issue":"4","key":"pone.0298226.ref006","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1161\/STROKEAHA.122.041738","article-title":"Stroke Recurrence and Antiplatelets in Posterior Versus Anterior Circulation Minor Stroke or Transient Ischemic Attack","volume":"54","author":"H Liu","year":"2023","journal-title":"Stroke"},{"key":"pone.0298226.ref007","first-page":"e924593","article-title":"Argatroban Increased the Basal Vein Drainage and Improved Outcomes in Acute Paraventricular Ischemic Stroke Patients.","volume":"26","author":"S Liu","year":"2020","journal-title":"Med Sci Monitor"},{"key":"pone.0298226.ref008","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jocn.2021.06.002","article-title":"Effects of argatroban therapy for stroke patients: A meta-analysis","volume":"90","author":"X Hou","year":"2021","journal-title":"J Clin Neurosci"},{"issue":"8","key":"pone.0298226.ref009","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1001\/jamasurg.2021.0546","article-title":"PRISMA Reporting Guidelines for Meta-analyses and Systematic Reviews","volume":"156","author":"S Arya","year":"2021","journal-title":"Jama Surg"},{"issue":"3","key":"pone.0298226.ref010","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1161\/01.STR.0000258355.23810.c6","article-title":"Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis","volume":"38","author":"JL Banks","year":"2007","journal-title":"Stroke"},{"issue":"9","key":"pone.0298226.ref011","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10654-010-9491-z","article-title":"Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses","volume":"25","author":"A. Stang","year":"2010","journal-title":"Eur J Epidemiol"},{"issue":"6","key":"pone.0298226.ref012","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1161\/STROKEAHA.117.016720","article-title":"Randomized, Multicenter Trial of ARTSS-2 (Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke).","volume":"48","author":"AD Barreto","year":"2017","journal-title":"Stroke"},{"issue":"8","key":"pone.0298226.ref013","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1001\/jama.2023.0550","article-title":"Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial.","volume":"329","author":"HS Chen","year":"2023","journal-title":"Jama-J Am Med Assoc"},{"key":"pone.0298226.ref014","doi-asserted-by":"crossref","first-page":"106233","DOI":"10.1016\/j.clineuro.2020.106233","article-title":"Early and long-term outcomes of argatroban use in patients with acute noncardioembolic stroke","volume":"198","author":"S Chen","year":"2020","journal-title":"Clin Neurol Neurosur"},{"key":"pone.0298226.ref015","doi-asserted-by":"crossref","first-page":"e341","DOI":"10.1016\/j.wneu.2019.08.151","article-title":"Safety and Feasibility of Using Argatroban Immediately After Mechanical Thrombectomy for Large Artery Occlusion.","volume":"132","author":"J Kim","year":"2019","journal-title":"World Neurosurg"},{"issue":"7","key":"pone.0298226.ref016","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1161\/01.STR.0000131549.20581.ba","article-title":"Argatroban anticoagulation in patients with acute ischemic stroke (ARGIS-1): a randomized, placebo-controlled safety study.","volume":"35","author":"MP LaMonte","year":"2004","journal-title":"Stroke"},{"issue":"7","key":"pone.0298226.ref017","doi-asserted-by":"crossref","first-page":"e2664","DOI":"10.1002\/brb3.2664","article-title":"Safety and preliminary efficacy of argatroban plus dual antiplatelet therapy for acute mild to moderate ischemic stroke with large artery atherosclerosis","volume":"12","author":"XQ Li","year":"2022","journal-title":"Brain Behav"},{"issue":"8","key":"pone.0298226.ref018","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1016\/j.jstrokecerebrovasdis.2018.03.016","article-title":"Retrospective Analysis of Argatroban in 353 Patients with Acute Noncardioembolic Stroke.","volume":"27","author":"H Oguro","year":"2018","journal-title":"J Stroke Cerebrovasc"},{"issue":"2","key":"pone.0298226.ref019","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1161\/STROKEAHA.115.011250","article-title":"Outcomes of Argatroban Treatment in Patients With Atherothrombotic Stroke: Observational Nationwide Study in Japan","volume":"47","author":"T Wada","year":"2016","journal-title":"Stroke"},{"issue":"1","key":"pone.0298226.ref020","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1186\/s12883-021-02435-x","article-title":"Early argatroban and antiplatelet combination therapy in acute non-lacunar single subcortical infarct associated with mild intracranial atherosclerosis","volume":"21","author":"PF Wang","year":"2021","journal-title":"Bmc Neurol"},{"issue":"1","key":"pone.0298226.ref021","first-page":"e19","article-title":"Dual Antiplatelet Therapy Plus Argatroban Prevents Early Neurological Deterioration in Branch Atherosclerosis Disease","volume":"53","author":"J Xu","year":"2022","journal-title":"Stroke"},{"key":"pone.0298226.ref022","first-page":"1420664637","article-title":"Effect of Argatroban Combined With Dual Antiplatelet Therapy on Early Neurological Deterioration in Acute Minor Posterior Circulation Ischemic Stroke.","volume":"26","author":"LS Zhou","year":"2020","journal-title":"Clin Appl Thromb-Hem"},{"issue":"1","key":"pone.0298226.ref023","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1023\/A:1015368126304","volume":"13","author":"S Kathiresan","year":"2002","journal-title":"Argatroban. 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Front Pharmacol"},{"issue":"10","key":"pone.0298226.ref030","first-page":"1229","volume":"38","author":"R Mao","year":"2022","journal-title":"Neuronal Death Mechanisms and Therapeutic Strategy in Ischemic Stroke. Neurosci Bull"},{"issue":"1","key":"pone.0298226.ref031","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.beha.2004.03.008","article-title":"Small-molecule direct antithrombins: argatroban.","volume":"17","author":"J Fareed","year":"2004","journal-title":"Best Pract Res Cl Ha"},{"issue":"14","key":"pone.0298226.ref032","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1016\/j.jcin.2016.06.002","article-title":"Dual-Antiplatelet Therapy: Why Stop Now?","volume":"9","author":"AK Jacobs","year":"2016","journal-title":"Jacc-Cardiovasc Inte."},{"issue":"4","key":"pone.0298226.ref033","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1177\/23969873221112279","article-title":"Timing of symptomatic intracranial hemorrhage after endovascular stroke treatment","volume":"7","author":"W van der Steen","year":"2022","journal-title":"Eur Stroke J"},{"issue":"3","key":"pone.0298226.ref034","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.ccc.2021.03.012","article-title":"Antithrombotic and Antiplatelet Drug Toxicity.","volume":"37","author":"DB Liss","year":"2021","journal-title":"Crit Care Clin."},{"issue":"1","key":"pone.0298226.ref035","article-title":"Practical Guide for Anticoagulant and Antiplatelet Reversal in Clinical Practice.","volume":"11","author":"M Aldhaeefi","year":"2023","journal-title":"Pharmacy-Basel."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0298226","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T18:29:38Z","timestamp":1709058578000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0298226"}},"subtitle":[],"editor":[{"given":"Oana","family":"Dumitrascu","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,27]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0298226","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,27]]}}}