Mismatch-Based Delayed Thrombolysis A Meta-Analysis
Mismatch-Based Delayed Thrombolysis A Meta-Analysis
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DOI：
10.1161/strokeaha.109.566869
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发表时间：
2010-01-01
期刊：
影响因子：
8.3
通讯作者：
Lees, Kennedy R.
中科院分区：
文献类型：
--
作者：
Mishra, Nishant K.;Albers, Gregory W.;Lees, Kennedy R.
背景和目的：溶栓治疗的临床获益随着卒中发作至治疗时间的延长而减少。使用“不匹配”成像来识别延迟治疗的患者具有表面有效性，并已用于病例系列和临床试验。我们进行了一项荟萃分析相关试验，以检查目前的证据是否支持延迟溶栓治疗的患者中选择的不匹配criteria. Methods，我们整理的结果数据后3小时中风发作的溶栓试验和不匹配的预处理成像的患者。我们选择的试验的基础上，一个系统的搜索网络的知识。我们比较了溶栓组和非溶栓组患者的有利结局、再灌注和/或再通、死亡率和症状性脑出血，以及卒中后3 - 6小时与6 - 9小时成功再灌注和临床表现的患者的有利结局概率。结果表示为校正比值比（a-OR）和95% CI。通过临床异质性、I-2（不一致性）和L 'Abbe plot.Results-We确定了描述DIAS、DIAS II、DEDAS、DEFUSE和EPITHET试验的文章，共纳入502例不匹配患者，溶栓时间超过3小时。成功再灌注患者的有利结局的合并a-OR更大（a-OR=5.2; 95% CI，3 - 9; I-2=0%）。溶栓治疗未显著改善有利的临床结局（a-OR=1.3; 95% CI，0.8 - 2.0; I-2=20.9%）。在接受溶栓治疗的患者中，再灌注/再通的几率增加（a-OR=3.0; 95% CI，1.6 - 5.8; I-2=25.7%）。合并数据显示溶栓后死亡率显著增加（a-OR=2.4; 95% CI，1.2 - 4.9; I-2=0%），但当我们排除临床开发中放弃的去氨普酶剂量数据时，这一点未得到证实（a-OR=1.6; 95% CI，0.7 - 3.7; I-2=0%）。溶栓后症状性脑出血明显增加（a-OR=6.5; 95% CI，1.2 - 35.4; I-2=0%），但排除放弃的去氨替普酶剂量后不显著（a-OR=5.4; 95% CI为0.9 ~ 31.8;结论：根据不匹配成像选择的患者中延迟溶栓与再灌注/再通增加相关。再通/再灌注与结局改善相关。然而，不匹配患者的延迟溶栓未被证实可改善临床结局，尽管仍有可能获得有用的临床获益。溶栓有明显的症状性脑出血风险，并可能增加死亡率。诊断不匹配的标准仍在不断发展。需要III期试验验证错配选择范例。在这些结果出现之前，延迟治疗，即使根据不匹配的选择，也不能作为常规护理的一部分。（中风。2010;41：e25-e33）。
Background and Purpose-Clinical benefit from thrombolysis is reduced as stroke onset to treatment time increases. The use of "mismatch" imaging to identify patients for delayed treatment has face validity and has been used in case series and clinical trials. We undertook a meta-analysis of relevant trials to examine whether present evidence supports delayed thrombolysis among patients selected according to mismatch criteria.Methods-We collated outcome data for patients who were enrolled after 3 hours of stroke onset in thrombolysis trials and had mismatch on pretreatment imaging. We selected the trials on the basis of a systematic search of the Web of Knowledge. We compared favorable outcome, reperfusion and/or recanalization, mortality, and symptomatic intracerebral hemorrhage between the thrombolyzed and nonthrombolyzed groups of patients and the probability of a favorable outcome among patients with successful reperfusion and clinical findings for 3 to 6 versus 6 to 9 hours from poststroke onset. Results are expressed as adjusted odds ratios (a-ORs) with 95% CIs. Heterogeneity was explored by test statistics for clinical heterogeneity, I-2 (inconsistency), and L'Abbe plot.Results-We identified articles describing the DIAS, DIAS II, DEDAS, DEFUSE, and EPITHET trials, giving a total of 502 mismatch patients thrombolyzed beyond 3 hours. The combined a-ORs for favorable outcomes were greater for patients who had successful reperfusion (a-OR=5.2; 95% CI, 3 to 9; I-2=0%). Favorable clinical outcome was not significantly improved by thrombolysis (a-OR=1.3; 95% CI, 0.8 to 2.0; I-2=20.9%). Odds for reperfusion/recanalization were increased among patients who received thrombolytic therapy (a-OR=3.0; 95% CI, 1.6 to 5.8; I-2=25.7%). The combined data showed a significant increase in mortality after thrombolysis (a-OR=2.4; 95% CI, 1.2 to 4.9; I-2=0%), but this was not confirmed when we excluded data from desmoteplase doses that were abandoned in clinical development (a-OR=1.6; 95% CI, 0.7 to 3.7; I-2=0%). Symptomatic intracerebral hemorrhage was significantly increased after thrombolysis (a-OR=6.5; 95% CI, 1.2 to 35.4; I-2=0%) but not significant after exclusion of abandoned doses of desmoteplase (a-OR=5.4; 95% CI, 0.9 to 31.8; I-2=0%).Conclusions-Delayed thrombolysis amongst patients selected according to mismatch imaging is associated with increased reperfusion/recanalization. Recanalization/reperfusion is associated with improved outcomes. However, delayed thrombolysis in mismatch patients was not confirmed to improve clinical outcome, although a useful clinical benefit remains possible. Thrombolysis carries a significant risk of symptomatic intracerebral hemorrhage and possibly increased mortality. Criteria to diagnose mismatch are still evolving. Validation of the mismatch selection paradigm is required with a phase III trial. Pending these results, delayed treatment, even according to mismatch selection, cannot be recommended as part of routine care. (Stroke. 2010;41:e25-e33.)