4.5小时时间窗之外的缺血性脑卒中溶栓治疗：随机临床试验的Meta分析
Thrombolysis for Ischemic Stroke Beyond the 4.5-Hour Window: A Meta-Analysis of Randomized Clinical Trials.
作者信息
Günkan Ahmet, Ferreira Marcio Yuri, Vilardo Marina, Scarcia Luca, Bocanegra-Becerra Jhon E, Cardoso Leonardo Januario Campos, Fabrini Paleare Luis F, de Oliveira Almeida Gustavo, Semione Gabriel, Ferreira Christian, Ciccio Gabriele, Mujanovic Adnan, Jabbour Pascal, Serulle Yafell, Nguyen Thanh N, Baron Jean-Claude
机构信息
Independent Researcher (A.G.).
Department of Neurosurgery, Lenox Hill Hospital/Northwell Health, New York, NY (M.Y.F., C.F., Y.S.).
出版信息
Stroke. 2025 Mar;56(3):580-590. doi: 10.1161/STROKEAHA.124.048536. Epub 2025 Jan 30.
BACKGROUND
A minority of patients with stroke qualify for intravenous thrombolysis (IVT) within 4.5-hour window. The safety and efficacy of IVT beyond this period have not been well studied.
METHODS
We systematically searched MEDLINE, Embase, Cochrane, and ClinicalTrials.gov for relevant randomized clinical trials. Randomized clinical trials comparing IVT versus standard medical care in patients with ischemic stroke beyond 4.5 hours of symptom onset or last known well without mechanical thrombectomy (MT) were included. Primary outcomes were excellent (modified Rankin Scale score of 0-1) and good (modified Rankin Scale score of 0-2) functional outcomes at 90 days, symptomatic intracerebral hemorrhage (sICH), and death at 90 days. Pooled odds ratios (ORs) with 95% CIs were calculated using a random-effects model. Heterogeneity was assessed by test and quantified by ² values.
RESULTS
Eight randomized clinical trials (1742 patients; mean age, 69.8±9 years, 63.5% men) were included. Compared with standard medical care, IVT achieved higher rates of excellent (OR, 1.43 [95% CI, 1.17-1.75]; =2.30; =0.94; =0%) and good functional outcomes (OR, 1.36 [95% CI, 1.12-1.66]; =2.07; =0.96; =0%) at 90 days but also increased sICH rates (OR, 4.25 [95% CI, 1.67-10.84], =0.48; =0.99; =0%). Mortality at 90 days did not significantly differ between treatment groups (OR, 1.28 [95% CI, 0.87-1.89]; =4.63; =0.59; =0%). Subanalyses yielded numerically higher odds of excellent functional outcomes when patients were selected with perfusion imaging (3 studies, OR, 1.45 [95% CI, 1.08-1.94]) compared with diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch (3 studies, OR, 1.34 [95% CI, 0.94-1.91]) and when treated with tenecteplase (3 studies, OR, 1.47 [95% CI, 1.06-2.04]) compared with alteplase (5 studies, OR, 1.38 [95% CI, 1.08-1.78]).
CONCLUSIONS
IVT for ischemic stroke beyond 4.5 hours, without MT, led to increased odds of excellent and good functional outcomes compared with standard medical care, despite higher odds of sICH, and a nonsignificant numerical increase in mortality.
背景
少数中风患者符合在4.5小时时间窗内进行静脉溶栓（IVT）的条件。在此时间段之外进行IVT的安全性和有效性尚未得到充分研究。
方法
我们系统检索了MEDLINE、Embase、Cochrane和ClinicalTrials.gov以查找相关随机临床试验。纳入了比较症状发作超过4.5小时或最后一次已知健康状态良好且未进行机械取栓（MT）的缺血性中风患者接受IVT与标准医疗护理的随机临床试验。主要结局为90天时的良好（改良Rankin量表评分为0 - 1）和较好（改良Rankin量表评分为0 - 2）功能结局、症状性脑出血（sICH）以及90天时的死亡情况。使用随机效应模型计算合并比值比（OR）及95%置信区间（CI）。通过I²检验评估异质性并以I²值进行量化。
结果
纳入了8项随机临床试验（1742例患者；平均年龄69.8±9岁，63.5%为男性）。与标准医疗护理相比，IVT在90天时实现了更高的良好（OR，1.43 [95% CI，1.17 - 1.75]；I² = 2.30；P = 0.94；I² = 0%）和较好功能结局发生率（OR，1.36 [95% CI，1.12 - 1.66]；I² = 2.07；P = 0.96；I² = 0%），但也增加了sICH发生率（OR，4.25 [95% CI，1.67 - 10.84]，I² = 0.48；P = 0.99；I² = 0%）。治疗组之间90天时的死亡率无显著差异（OR，1.28 [95% CI，0.87 - 1.89]；I² = 4.63；P = 0.59；I² = 0%）。亚组分析显示，与弥散加权成像 - 液体衰减反转恢复不匹配（3项研究，OR，1.34 [95% CI，0.94 - 1.91]）相比，采用灌注成像选择患者时（3项研究，OR，1.45 [95% CI，1.08 - 1.94]）以及与阿替普酶（5项研究，OR，1.38 [95% CI，1.08 - 1.78]）相比，采用替奈普酶治疗时（3项研究，OR，1.47 [95% CI，1.06 - 2.04]），良好功能结局的比值在数值上更高。
结论
对于超过4.5小时且未进行MT的缺血性中风患者，IVT与标准医疗护理相比，尽管sICH发生率更高且死亡率在数值上有非显著增加，但导致良好和较好功能结局的几率增加。
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