Efficacy and Safety of Various Intravenous Thrombolytics for Acute Ischemic Stroke (AIS) at Various Dosages: A Systematic Review and Network Meta-Analysis.

IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Neurology and Therapy Pub Date : 2025-04-01 Epub Date: 2024-12-11 DOI:10.1007/s40120-024-00684-9
Yibin Hu, Shengxian Wu, Haixuan Zhang, Kangfeng Wang, Lijuan Zhang, Yizheng Ma, He Li
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Abstract

Background: Currently, there is limited evidence on the efficacy and safety of various thrombolytic drugs at different dosages for the treatment of acute ischemic stroke (AIS). From current randomized clinical trials, the optimal type and dosage of thrombolytics for patients with AIS are unclear.

Methods: This systematic review was registered in PROSPERO (CRD42024563757). We searched four databases using a combination of keywords that contained various intravenous thrombolytics, as well as acute ischemic stroke. Only data from participants with AIS treated with various intravenous thrombolytics within the 4.5-h time window were included. Among initially identified studies, 16 met the selection criteria. Network meta-analysis was conducted for efficacy (90 day modified Rankin scale score) and safety (intracranial hemorrhage events, mortality at 90 days) using Stata 17.0 software, with a fixed-effects model. Cochrane risk of bias tool assessed all risk of bias domains, and the CINeMA Evidence Assessment Tool evaluated the level of evidence for each outcome.

Results: A total of 9056 studies were retrieved through the literature search, and 12,792 patients screened from 16 randomized controlled trials were included in the network meta-analysis. The risk of bias in the included studies ranged from moderate to low. The network meta-analysis results indicated that reteplase at 18 + 18 mg ranked highest in efficacy, though its safety was lower compared to 0.25 mg/kg tenecteplase and alteplase. The dose of 0.25 mg/kg tenecteplase emerged as the optimal dose, demonstrating both superior efficacy and a lower risk of bleeding compared to alteplase, making it a potential alternative to alteplase. The dose of 50 mg prourokinase was associated with the highest risk of symptomatic intracranial hemorrhage and was inferior to reteplase in terms of both efficacy and safety. The CINeMA Evidence Assessment Tool identified one outcome with a high level of evidence, several with moderate levels, and the remainder with low levels.

Conclusions: Reteplase at 18 + 18 mg may be more suitable for patients with lower incidence of adverse events evaluated by physicians. Compared to 0.9 mg/kg alteplase, 0.25 mg/kg tenecteplase is more effective, with the lowest risk of intracranial hemorrhage. However, as tenecteplase's dosages increase (0.32 mg/kg and 0.4 mg/kg), its efficacy in improving neurological deficits decreases, while the risk of intracranial hemorrhage and death (especially at 0.4 mg/kg) increases. Clinicians are supposed to carefully assess the needs of patients with AIS and the risks then choose decent thrombolytics.

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不同剂量静脉溶栓剂治疗急性缺血性卒中(AIS)的疗效和安全性:系统综述和网络荟萃分析
背景:目前,各种不同剂量的溶栓药物治疗急性缺血性脑卒中(AIS)的疗效和安全性证据有限。从目前的随机临床试验来看,AIS患者溶栓药物的最佳类型和剂量尚不清楚。方法:本系统评价在PROSPERO注册(CRD42024563757)。我们使用包含各种静脉溶栓剂和急性缺血性中风的关键词组合搜索了四个数据库。仅纳入了4.5小时时间窗内接受各种静脉溶栓治疗的AIS患者的数据。在最初确定的研究中,有16项符合选择标准。采用Stata 17.0软件对疗效(90天修正Rankin量表评分)和安全性(颅内出血事件、90天死亡率)进行网络meta分析,采用固定效应模型。Cochrane偏倚风险评估工具评估了所有偏倚域的风险,CINeMA证据评估工具评估了每个结果的证据水平。结果:通过文献检索共检索到9056项研究,从16项随机对照试验中筛选出12792例患者纳入网络meta分析。纳入研究的偏倚风险从中等到低不等。网络荟萃分析结果显示,18 + 18 mg的瑞替普酶的疗效最高,但其安全性低于0.25 mg/kg的替奈普酶和阿替普酶。与阿替普酶相比,0.25 mg/kg的替奈普酶是最佳剂量,显示出更好的疗效和更低的出血风险,使其成为阿替普酶的潜在替代品。50mg prorokinase的剂量与症状性颅内出血的最高风险相关,并且在有效性和安全性方面都不如reteplase。CINeMA证据评估工具确定了一个结果具有高水平证据,几个结果具有中等水平证据,其余结果具有低水平证据。结论:Reteplase 18 + 18mg可能更适合于医生评价不良事件发生率较低的患者。与0.9 mg/kg阿替普酶相比,0.25 mg/kg替奈普酶更有效,颅内出血风险最低。然而,随着替奈普酶剂量的增加(0.32 mg/kg和0.4 mg/kg),其改善神经功能缺损的功效下降,而颅内出血和死亡的风险(特别是0.4 mg/kg)增加。临床医生应该仔细评估AIS患者的需求和风险,然后选择合适的溶栓药物。
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来源期刊
Neurology and Therapy
Neurology and Therapy CLINICAL NEUROLOGY-
CiteScore
5.40
自引率
8.10%
发文量
103
审稿时长
6 weeks
期刊介绍: Aims and Scope Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice. Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Neurology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted, it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model, this allows for the rapid and efficient communication of the latest research and reviews to support scientific discovery and clinical practice. Open Access All articles published by Neurology and Therapy are open access. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts. Digital Features and Plain Language Summaries Neurology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. For examples of digital features please visit our showcase page https://springerhealthcare.com/expertise/publishing-digital-features/ Publication Fees Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of €5250/$6000/£4300. The journal will consider fee discounts and waivers for developing countries and this is decided on a case-by-case basis. Peer Review Process Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria. At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials and Letters which are generally reviewed by one member of the Editorial Board. Where reviews conflict, an Editorial Board Member will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed. Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised, it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor, and authors are welcome to make rebuttals against individual reviewer comments, if appropriate. Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors'' or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. Please see here for further information on preprint sharing: https://www.springer.com/gp/authors-editors/journal-author/journal-author-helpdesk/submission/1302#c16721550 Copyright Neurology and Therapy is published under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0. Contact For more information about the journal, including pre-submission enquiries, please contact managing editor Lydia Alborn at lydia.alborn@springer.com.
期刊最新文献
Correction: Efficacy and Safety of Various Intravenous Thrombolytics for Acute Ischemic Stroke (AIS) at Various Dosages: A Systematic Review and Network Meta-Analysis. Efficacy and Safety of Various Intravenous Thrombolytics for Acute Ischemic Stroke (AIS) at Various Dosages: A Systematic Review and Network Meta-Analysis. Measurement Properties of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia. Content Validity of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia. A Podcast on the Rhythms of Healing: Patient and Physician Insights on Art, Music, Dance Therapy and Creativity in Parkinson's Disease.
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