Palaiodimou Lina, Papageorgiou Nikolaos M, Safouris Apostolos, Theodorou Aikaterini, Bakola Eleni, Chondrogianni Maria, Papagiannopoulou Georgia, Kargiotis Odysseas, Psychogios Klearchos, Polyzogopoulou Eftihia, Magoufis Georgios, Velonakis Georgios, Rudolf Jobst, Mitsias Panayiotis, Tsivgoulis Georgios
Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National & Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece.
Stroke Unit, Metropolitan Hospital, 18547 Piraeus, Greece.
J Clin Med. 2025 Aug 4;14(15):5474. doi: 10.3390/jcm14155474.
While intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke (AIS) within 4.5 h of symptom onset, many patients present beyond this time window. Recent trials suggest that IVT may be both effective and safe in selected patients treated after the standard time window. We searched MEDLINE, Scopus, and ClinicalTrials.gov for randomized-controlled clinical trials (RCTs) and individual patient-data meta-analyses (IPDMs) of RCTs comparing IVT plus best medical treatment (BMT) to BMT alone in AIS patients who were last-known-well more than 4.5 h earlier. The primary efficacy outcome was a 90-day excellent functional outcome [modified Rankin Scale (mRS)-scores of 0-1]. Secondary efficacy outcomes included good functional outcome (mRS-scores 0-2) and reduced disability (≥1-point reduction across all mRS-strata). The primary safety outcome was symptomatic intracranial hemorrhage (sICH); secondary safety outcomes were any ICH and 3-month all-cause mortality. Subgroup analyses were performed stratified by different thrombolytics, time-windows, imaging modalities, and affected circulation. Nine studies were included, comprising 1660 patients in the IVT-group and 1626 patients in the control-group. IVT significantly improved excellent functional outcome (RR = 1.24; 95%CI:1.14-1.34; I = 0%) and good functional outcome (RR = 1.18; 95%CI:1.05-1.33; I = 70%). IVT was associated with increased odds of reduced disability (common OR = 1.3; 95%CI:1.15-1.46; I = 0%) and increased risk of sICH (RR = 2.75; 95%CI:1.49-5.05; I = 0%). The rates of any ICH and all-cause mortality were similar between the two groups. No significant subgroup differences were documented. IVT in the extended time window improved functional outcomes without increasing mortality, despite a higher rate of sICH.
虽然静脉溶栓（IVT）是症状发作4.5小时内急性缺血性卒中（AIS）的标准治疗方法，但许多患者就诊时已超出此时间窗。近期试验表明，在标准时间窗后接受治疗的部分患者中，IVT可能既有效又安全。我们检索了MEDLINE、Scopus和ClinicalTrials.gov，以查找随机对照临床试验（RCT）以及对最后一次情况良好时间超过4.5小时的AIS患者比较IVT加最佳药物治疗（BMT）与单纯BMT的RCT的个体患者数据荟萃分析（IPDM）。主要疗效结局为90天良好功能结局[改良Rankin量表（mRS）评分0 - 1]。次要疗效结局包括良好功能结局（mRS评分0 - 2）和残疾程度降低（所有mRS分层中降低≥1分）。主要安全结局为症状性颅内出血（sICH）；次要安全结局为任何颅内出血和3个月全因死亡率。根据不同溶栓药物、时间窗、成像方式和受累循环进行亚组分析。纳入9项研究，IVT组1660例患者，对照组1626例患者。IVT显著改善了良好功能结局（RR = 1.24；95%CI：1.14 - 1.34；I² = 0%）和良好功能结局（RR = 1.18；95%CI：1.05 - 1.33；I² = 70%）。IVT与残疾程度降低几率增加相关（共同OR = 1.3；95%CI：1.15 - 1.46；I² = 0%），且sICH风险增加（RR = 2.75；95%CI：1.49 - 5.05；I² = 0%）。两组的任何颅内出血率和全因死亡率相似。未记录到显著的亚组差异。在延长时间窗内进行IVT可改善功能结局且不增加死亡率，尽管sICH发生率较高。
