急性缺血性卒中静脉溶栓治疗的安全性：一项系统综述和网络meta分析。

IF 7.4 2区医学 Q1 CLINICAL NEUROLOGY

CNS drugs Pub Date : 2025-09-30 DOI:10.1007/s40263-025-01228-x

Xuefan Yao, Kehui Ma, Benke Zhao, Aini He, Wei Sun, Jiaxin Gao, Houlin Lai, Xue Wang, Yuan Wang, Haiqing Song

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引用次数: 0

摘要

背景：静脉溶栓（IVT）治疗的安全性影响急性缺血性卒中（AIS）的总体疗效，但各种静脉溶栓治疗的安全性研究仍然较少。在这项研究中，我们通过对AIS患者IVT后安全性结果的系统回顾和荟萃分析，对各种IVT治疗的安全性进行了排名。方法：该网络荟萃分析已在国际前瞻性系统评价登记册(PROSPERO; no。CRD42024544617)。IVT治疗AIS的3期随机对照试验来自Embase、Ovid Medline和Cochrane图书馆。主要结局包括总严重不良事件（SAEs）、症状性颅内出血（sICH）和3个月死亡率。结果：网络荟萃分析纳入了21项SAEs研究，21项siich研究，34项死亡率研究，无异质性（I2 = 0%; I2 = 0%; I2 = 15.86%）。与非溶栓相比，阿替普酶0.9 mg/kg和替奈替普酶0.25 mg/kg与更多的sae（风险差[RD] 0.03, 95%可信区间[CI] 0.01 ~ 0.05; RD 0.04, 95%可信区间[CI 0.01 ~ 0.06）、sICH （RD 0.02, 95% CI 0.01 ~ 0.03; RD 0.02, 95% CI 0.01 ~ 0.03）和死亡率（RD 0.01, 95% CI 0.00 ~ 0.03; RD 0.02, 95% CI 0.00 ~ 0.03）相关。Nonimmunogenic重组葡萄球菌激酶(nSta) 10毫克导致节约少于non-thrombolysis (RD - 0.11, 95% CI, 0.21 - 0.01),重组人类prourokinase (rhPro-UK) 35毫克(RD - 0.12, 95% CI, 0.22 - 0.02),溶栓0.9毫克/公斤(RD - 0.14, 95% CI, 0.23 - 0.04),和tenecteplase 0.25毫克/公斤(RD - 0.15, 95% CI, 0.24 - 0.05)和西奇比tenecteplase 0.25毫克/公斤(RD - 0.05, 95%可信区间0.10到0.00)。虽然rhPro-UK 35 mg比非溶栓导致更多的siich (RD 0.01, 95% CI 0.00-0.02)，但与阿替普酶0.9 mg/kg （RD - 0.01, 95% CI -0.02至0.00）和替尼替普酶0.25 mg/kg （RD - 0.01, 95% CI -0.02至- 0.01）相比，它与siich发生率较低相关。与阿替普酶0.6 mg/kg相比，阿替普酶0.9 mg/kg和替奈普酶0.25 mg/kg导致的sae （RD 0.04, 95% CI 0.01 ~ 0.07; RD 0.05, 95% CI 0.01 ~ 0.08）和siich （RD 0.01, 95% CI 0.00~ 0.02; RD 0.02, 95% CI 0.01 ~ 0.03）发生率更高。通过组织窗评估，给药超过4.5小时后，与非溶栓相比，替替普酶0.25 mg/kg和阿替普酶0.6 mg/kg与更高的死亡率无关。结论：阿替普酶0.6 mg/kg、rhPro-UK 35 mg和nSta 10 mg是更安全的IVT选择。通过组织窗评估，替奈普酶0.25 mg/kg和阿替普酶0.6 mg/kg的效果优于4.5 h。

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Safety Outcomes Following Intravenous Thrombolysis in Acute Ischemic Stroke: A Systematic Review and Network Meta-analysis.

Background: Safety outcomes following intravenous thrombolysis (IVT) impact overall efficacy in acute ischemic stroke (AIS), yet safety profiles of various IVT treatments remain less studied. In this study, we ranked safety profiles of various IVT treatments through a systematic review and meta-analysis of safety outcomes following IVT in AIS.

Methods: This network meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO; no. CRD42024544617). Phase 3 randomized controlled trials on IVT in AIS from Embase, Ovid Medline, and Cochrane Library were included. Primary outcomes included total serious adverse events (SAEs), symptomatic intracranial hemorrhage (sICH), and 3-month mortality.

Results: Network meta-analysis involved 21 studies for total SAEs, 21 for sICH, and 34 for mortality with no heterogeneity (I² = 0%; I² = 0%; I² = 15.86%). Compared with non-thrombolysis, alteplase 0.9 mg/kg and tenecteplase 0.25 mg/kg were associated with more SAEs (risk difference [RD] 0.03, 95% confidence interval [CI] 0.01-0.05; RD 0.04, 95% CI 0.01-0.06), sICH (RD 0.02, 95% CI 0.01-0.03; RD 0.02, 95% CI 0.01-0.03), and mortality (RD 0.01, 95% CI 0.00-0.03; RD 0.02, 95% CI 0.00-0.03). Nonimmunogenic recombinant staphylokinase (nSta) 10 mg resulted in fewer SAEs than non-thrombolysis (RD - 0.11, 95% CI - 0.21 to - 0.01), recombinant human prourokinase (rhPro-UK) 35 mg (RD - 0.12, 95% CI - 0.22 to - 0.02), alteplase 0.9 mg/kg (RD - 0.14, 95% CI - 0.23 to - 0.04), and tenecteplase 0.25 mg/kg (RD - 0.15, 95% CI - 0.24 to - 0.05) and less sICH than tenecteplase 0.25 mg/kg (RD - 0.05, 95% CI - 0.10 to 0.00). Although rhPro-UK 35 mg resulted in more sICH than non-thrombolysis (RD 0.01, 95% CI 0.00-0.02), it was associated with a lower rate of sICH compared with alteplase 0.9 mg/kg (RD - 0.01, 95% CI - 0.02 to 0.00) and tenecteplase 0.25 mg/kg (RD - 0.01, 95% CI - 0.02 to - 0.01). Compared with alteplase 0.6 mg/kg, alteplase 0.9 mg/kg and tenecteplase 0.25 mg/kg resulted in more SAEs (RD 0.04, 95% CI 0.01-0.07; RD 0.05, 95% CI 0.01-0.08) and sICH (RD 0.01, 95% CI 0.00-0.02; RD 0.02, 95% CI 0.01-0.03). When administered beyond 4.5 h with tissue window assessment, tenecteplase 0.25 mg/kg and alteplase 0.6 mg/kg were not associated with higher rates of mortality compared with non-thrombolysis.

Conclusions: Alteplase 0.6 mg/kg, rhPro-UK 35 mg, and nSta 10 mg were safer IVT options. Tenecteplase 0.25 mg/kg and alteplase 0.6 mg/kg were preferable beyond 4.5 h with tissue window assessment.

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来源期刊

CNS drugs 医学-精神病学

CiteScore

12.00

自引率

3.30%

发文量

审稿时长

6-12 weeks

期刊介绍： CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs 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 important medical advances.