Soheil Rahmati, Mohammadreza Alinejadfard, Yasaman Zarinfar, Amir Moradi, Amir Ghabousian, Ali Moradi, Kimia Najafi, Fady Iskander, Azeem Latib, Toshiki Kuno, Preethi Ramchand, Kaveh Hosseini
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引用次数: 0
Abstract
Background and objectives: Intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke within 4.5 hours of onset. However, imaging-based selection may extend the treatment window. This systematic review and meta-analysis evaluated the efficacy and safety of IVT administered beyond 4.5 hours after stroke onset or last known well (LKW) in patients selected based on imaging findings.
Methods: A comprehensive search of PubMed, Scopus, and Cochrane Library was performed to identify randomized controlled trials comparing IVT with alteplase or tenecteplase (TNK) administered >4.5 hours after stroke onset/LKW vs standard care. Primary outcomes were 3-month excellent (modified Rankin Scale [mRS] 0-1) functional outcome and symptomatic intracranial hemorrhage (sICH). Secondary outcomes included good (mRS 0-2) functional outcome, recanalization, and 3-month mortality. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analysis assessed differences between alteplase and TNK.
Results: Fourteen studies involving 4,944 patients were included. The mean age was 69.8 years, 58.2% were male, the median National Institutes of Health Stroke Scale score was 9, and 12.3% received preplanned endovascular thrombectomy (EVT). A total of 2,492 patients received IVT in an extended time window (4.5-24 hours). Compared with standard care, extended IVT was associated with higher odds of achieving an excellent functional outcome (OR: 1.43 [95% CI 1.25-1.63]), a good functional outcome (OR: 1.25 [95% CI 1.11-1.40]), and recanalization (OR: 3.28 [95% CI 2.09-5.16]). There was no difference in 3-month mortality (OR: 1.21 [95% CI 0.95-1.53]). However, IVT increased the risk of sICH (OR: 2.51 [95% CI 1.47-4.28]). Sensitivity analysis excluding patients who received EVT showed no impact on the outcomes. TNK exhibited similar efficacy to alteplase but showed potentially lower odds of sICH (OR: 1.96, 95% CI 1.06-3.64) compared with alteplase (OR: 5.29, 95% CI 1.80-15.57); however, the subgroup difference was not significant (p = 0.11).
Discussion: Among patients selected based on imaging, 4.5-24 hours after stroke onset/LKW, IVT improves outcomes despite an increased risk of sICH. TNK showed similar efficacy to alteplase, with a possible lower risk of sICH; however, direct comparisons in future trials are needed.
背景和目的：静脉溶栓（IVT）是急性缺血性卒中4.5小时内的标准治疗方法。然而，基于成像的选择可能会延长治疗窗口。本系统综述和荟萃分析评估了基于影像学结果选择的患者在卒中发作或最后已知时间（LKW）后超过4.5小时给予IVT的疗效和安全性。方法：对PubMed、Scopus和Cochrane文库进行全面检索，以确定随机对照试验，比较IVT与卒中发作后4.5小时给予阿替普酶或替奈普酶(TNK) /LKW与标准治疗的差异。主要结果为3个月功能预后良好（改良Rankin量表[mRS] 0-1）和症状性颅内出血（siich）。次要结局包括良好（mRS 0-2）的功能结局、再通和3个月死亡率。采用随机效应模型计算合并优势比（ORs）和95%置信区间（ci）。亚组分析评估阿替普酶和TNK的差异。结果：纳入14项研究，共4944例患者。平均年龄为69.8岁，58.2%为男性，美国国立卫生研究院卒中量表评分中位数为9分，12.3%接受了预先计划的血管内血栓切除术（EVT）。共有2492例患者在延长的时间窗口（4.5-24小时）内接受了IVT治疗。与标准治疗相比，延长IVT与获得良好功能结果（OR: 1.43 [95% CI 1.25-1.63]）、良好功能结果（OR: 1.25 [95% CI 1.11-1.40]）和再通（OR: 3.28 [95% CI 2.09-5.16]）的几率较高相关。3个月死亡率无差异（OR: 1.21 [95% CI 0.95-1.53]）。然而，IVT增加了sICH的风险（OR: 2.51 [95% CI 1.47-4.28]）。排除EVT患者的敏感性分析显示对结果没有影响。TNK表现出与阿替普酶相似的疗效，但与阿替普酶（OR: 5.29, 95% CI 1.80-15.57）相比，其潜在的sICH几率更低（OR: 1.96, 95% CI 1.06-3.64）；但亚组间差异无统计学意义（p = 0.11）。讨论：在基于影像学选择的患者中，在卒中发作/LKW后4.5-24小时，IVT改善了结果，尽管增加了sICH的风险。TNK的疗效与阿替普酶相似，但发生sICH的风险可能更低；然而，需要在未来的试验中进行直接比较。
期刊介绍：
Neurology® Genetics is an online open access journal publishing peer-reviewed reports in the field of neurogenetics. The journal publishes original articles in all areas of neurogenetics including rare and common genetic variations, genotype-phenotype correlations, outlier phenotypes as a result of mutations in known disease genes, and genetic variations with a putative link to diseases. Articles include studies reporting on genetic disease risk, pharmacogenomics, and results of gene-based clinical trials (viral, ASO, etc.). Genetically engineered model systems are not a primary focus of Neurology® Genetics, but studies using model systems for treatment trials, including well-powered studies reporting negative results, are welcome.
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