Exploring Between-Study Heterogeneity in Extended-Window IV Thrombolysis for Acute Ischemic Stroke: A Meta-Analysis of 18 Randomized Controlled Trials.

Emerging evidence supports its use beyond this time window, leading to expanded recommendations for selected patients presenting between 4.5 and 24 hours.

新兴的证据支持在这一时间窗口之外使用IVT，导致对于在4.5至24小时之间出现的选定患者有扩展的推荐。

We performed a systematic reviewand meta-analysisto evaluate IVT in the 4.5- to 24-hour window and to explore sources of between-study heterogeneity.

我们进行了一项系统评价和荟萃分析，以评估4.5至24小时窗口期内的静脉溶栓治疗，并探索研究间异质性的来源。

Methods

We searched MEDLINE, Cochrane Library, and ClinicalTrials.gov from inception through February 2026.

我们从开始至2026年2月，检索了MEDLINE、Cochrane图书馆和ClinicalTrials.gov。

Eligible studies were randomized controlled trials (RCTs) or individual patient-data meta-analyses of RCTs comparing IVT with control in patients with AIS presenting beyond 4.5 hours from last known well.

符合条件的研究是随机对照试验（RCTs）或对比较静脉溶栓（IVT）与对照组的RCTs进行个体患者数据荟萃分析，研究对象为发病超过4.5小时后接受治疗的急性缺血性中风（AIS）患者。

The primary outcome was excellent functional recovery, defined as a modified Rankin Scale (mRS) of 0-1 at 90 days.

主要结果是优秀功能恢复，定义为90天时改良Rankin量表（mRS）评分为0-1。

Secondary outcomes included functional independence (mRS of 0-2 at 90 days); change in mRS disability, quantified as the common odds ratio (OR) for a 1-point improvement across the full ordinal mRS distribution (ordinal analysis); and safety measures such as 90-day mortality and symptomatic intracranial hemorrhage (sICH).

次要结果包括功能独立性（90天时mRS评分为0-2）；mRS残疾程度的变化，通过全序贯mRS分布中1分改善的共同比值比（OR）进行量化（序贯分析）；以及安全性指标，如90天内的死亡率和症状性颅内出血（sICH）。

Risk ratios (RRs) with 95% CIs were pooled.

风险比（RRs）及其95%置信区间（CIs）被汇总。

Multivariable meta-regression simultaneously modeled thrombolytic agent, endovascular thrombectomy context, and territory to disentangle confounded predictors.

多变量元回归同时模拟了溶栓剂、血管内血栓切除术的背景以及领域，以解开混杂的预测因素。

Results

Fifteen studies representing 18 RCTs and encompassing 5,168 patients were included in the primary analysis.

共有15项研究代表了18个随机对照试验，涵盖了5,168名患者，被纳入主要分析。

Of the 18 included RCTs, 11 required advanced perfusion imaging (CTP or MRP mismatch) or diffusion-weighted imaging/fluid-attenuated inversion recovery mismatch to confirm salvageable tissue; the remaining 7 permitted noncontrast CT/CT angiography-based selection.

在纳入的18项随机对照试验中，有11项需要使用高级灌注成像（CTP或MRP不匹配）或扩散加权成像/液体衰减反转恢复不匹配来确认可挽救的组织；其余7项允许使用无对比剂CT/CT血管造影进行选择。

IVT significantly improved excellent functional outcome at 90 days (mRS 0-1; 40.3% vs 33.2%, RR 1.21; 95% CI 1.13-1.30; p < 0.001; number needed to treat [NNT] = 14) and good functional outcome (mRS 0-2; 54.5% vs 50.1%, RR 1.09; 95% CI 1.04-1.15; p < 0.001; NNT = 23).

静脉溶栓治疗显著提高了90天的良好功能结果（mRS 0-1；40.3%对比33.2%，相对风险1.21；95%置信区间1.13-1.30；p < 0.001；需要治疗的患者数[NNT] = 14）和良好的功能结果（mRS 0-2；54.5%对比50.1%，相对风险1.09；95%置信区间1.04-1.15；p < 0.001；NNT = 23）。

IVT was associated with significantly greater odds of reduced disability across the full mRS spectrum (common OR 1.18; 95% CI 1.07-1.32; p = 0.004).

静脉溶栓治疗与降低残疾程度（mRS全谱）的显著增加几率相关（共同OR 1.18; 95% 置信区间 1.07-1.32; p = 0.004）。

IVT increased the risk of sICH (3.2% vs 1.4%; RR 1.90; 95% CI 1.28-2.84; p = 0.002; number needed to harm = 57) but did not increase 90-day mortality (13.7% vs 13.0% RR 1.04; 95% CI 0.92-1.18; p = 0.53).

静脉溶栓治疗增加了症状性颅内出血（sICH）的风险（3.2%对比1.4%；相对风险RR 1.90; 95% 置信区间 1.28-2.84; p = 0.002; 危害人数为57），但并未增加90天的死亡率（13.7%对比13.0%；相对风险RR 1.04; 95% 置信区间 0.92-1.18; p = 0.53）。

Meta-regression showed that thrombectomy (β = -0.275, p = 0.012 for mRS shift; β = -0.186, p = 0.032 for mRS 0-2) is the primary driver of between-study heterogeneity, explaining 66%-100% of intertrial variance.

元回归分析显示，血栓切除术（对于mRS转变的β = -0.275，p = 0.012；对于mRS 0-2的β = -0.186，p = 0.032）是研究间异质性的主要驱动因素，解释了66%-100%的试验间变异。

Discussion

Extended-window IVT improves functional outcomes across a wider spectrum of stroke subgroups than previously recognized.

扩展窗口期的静脉溶栓治疗在比以往认识更广泛的中风亚组中改善了功能结果。

The benefit seems greatest for patients with more severe strokes in settings where thrombectomy is unavailable, providing the evidence base for offering a critical reperfusion strategy for the substantial proportion of patients worldwide who lack timely access to thrombectomy.

对于那些无法接受血栓切除术的患者，对于更严重中风的患者益处似乎最大，为全世界缺乏及时接受血栓切除术的大量患者提供了一个关键的再灌注策略的证据基础。

classification_of_evidence

This study provides American Academy of Neurology Class I evidence that IVT administered 4.5-24 hours after moderate-to-severe AIS onset in patients with salvageable tissue, where thrombectomy is not readily available, improves functional outcome at 90 days without increasing mortality.

这项研究提供了美国神经病学学会I级证据，表明在中度至重度急性缺血性中风发作后4.5-24小时内对有可挽救组织的患者进行静脉溶栓治疗，在没有血栓切除术的情况下，可以改善90天的功能结果，而不会增加死亡率。