替奈普酶、阿替普酶和血管内血栓切除术在延长时间窗急性缺血性卒中伴颅内大血管闭塞中的应用：一项贝叶斯网络荟萃分析。
完整摘要 · 中文译文
背景与目的：在影像学筛选的、超过4.5小时时间窗的急性缺血性卒中患者中，静脉溶栓药物、血管内血栓切除术（EVT）及桥接治疗的效果比较仍不明确。我们在区分经证实的颅内大血管闭塞（LVO）证据与更广泛的混合人群的同时，比较了这些治疗策略。 方法：我们检索了PubMed、Embase、Web of Science和Cochrane图书馆，纳入评估卒中发病后或最后已知正常时间4.5至24小时内进行再灌注治疗的随机试验。主要网络分析纳入要求经证实的颅内LVO或基底动脉闭塞（BAO）的试验。前循环LVO网络和全可用网络作为敏感性和探索性分析进行检验。采用贝叶斯随机效应一致性模型估计比值比（OR）及其95%可信区间（CrIs）。主要结局为功能独立，定义为90天时改良Rankin量表评分为0至2分。 结果：共纳入15项随机试验，其中8项纳入主要经证实的LVO/BAO网络分析。与安慰剂或最佳药物治疗相比，EVT显著改善功能独立（OR，2.93 [95% CrI，1.40-6.53]）和极佳功能结局（定义为mRS 0至1）（OR，2.22 [95% CrI，1.30-4.11]），降低90天死亡率（OR，0.71 [95% CrI，0.50-0.98]），并增加约24小时时试验定义的再通或再灌注（OR，5.27 [95% CrI，1.83-16.04]）；症状性颅内出血（sICH）也增加（OR，2.65 [95% CrI，1.28-5.81]）。与EVT相比，t 依奈替普酶联合EVT在功能独立性（OR，1.10 [95% CrI，0.34-3.52]）和极佳结局（OR，1.16 [95% CrI，0.52-2.64]）方面显示出数值上有利但统计学上不确切的估计。对2项试验的直接成对分析同样不确切。单独使用依奈替普酶与安慰剂或最佳药物治疗相比未显示出明确差异。在前循环敏感性分析和所有可用探索性网络分析中，结果方向一致。 结论：在经影像学筛选、确认存在颅内LVO或BAO且在发病或最后已知正常后4.5至24小时接受治疗的患者中，EVT与安慰剂或最佳药物治疗相比具有最一致获益证据。依奈替普酶联合EVT显示出有利但不精确的估计，网络分析和直接成对分析均未确立其优于单独EVT。桥接依奈替普酶的增量获益仍不确定。
完整摘要 · 英文原文
BACKGROUND AND PURPOSE: The comparative effects of intravenous thrombolytic agents, endovascular thrombectomy (EVT), and bridging therapy in imaging-selected patients with acute ischemic stroke treated beyond 4.5 hours remain uncertain. We compared these strategies while distinguishing confirmed large-vessel occlusion (LVO) evidence from broader mixed populations. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for randomized trials evaluating reperfusion treatments administered 4.5 to 24 hours after stroke onset or last known well. The primary network included trials requiring confirmed intracranial LVO or basilar artery occlusion (BAO). An anterior-circulation LVO network and an all-available network were examined as sensitivity and exploratory analyses. Bayesian random-effects consistency models estimated odds ratios (ORs) with 95% credible intervals (CrIs). The primary outcome was functional independence, defined as a modified Rankin Scale score of 0 to 2 at 90 days. RESULTS: Fifteen randomized trials were included, of which 8 contributed to the primary confirmed LVO/BAO network. Compared with placebo or best medical care, EVT significantly improved functional independence (OR, 2.93 [95% CrI, 1.40-6.53]) and excellent functional outcome, defined as mRS 0 to 1 (OR, 2.22 [95% CrI, 1.30-4.11]), reduced 90-day mortality (OR, 0.71 [95% CrI, 0.50-0.98]), and increased trial-defined recanalization or reperfusion at approximately 24 hours (OR, 5.27 [95% CrI, 1.83-16.04]); sICH was also increased (OR, 2.65 [95% CrI, 1.28-5.81]). Compared with EVT, tenecteplase plus EVT showed numerically favorable but statistically inconclusive estimates for functional independence (OR, 1.10 [95% CrI, 0.34-3.52]) and excellent outcome (OR, 1.16 [95% CrI, 0.52-2.64]). Direct pairwise analyses of 2 trials were similarly inconclusive. Tenecteplase alone did not show clear differences from placebo or best medical care. Findings were directionally consistent in the anterior-circulation sensitivity and all-available exploratory networks. CONCLUSIONS: Among imaging-selected patients with confirmed intracranial LVO or BAO treated 4.5 to 24 hours after onset or last known well, EVT had the most consistent evidence of benefit versus placebo or best medical care. Tenecteplase plus EVT showed favorable but imprecise estimates, and neither network nor direct pairwise analyses established superiority over EVT alone. The incremental benefit of bridging tenecteplase remains uncertain.