Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association.
Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association.
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DOI：
10.1161/strokeaha.109.192535
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发表时间：
2009-08
期刊：
影响因子：
8.3
通讯作者：
American Heart Association Stroke Council
中科院分区：
文献类型：
--
作者：
Del Zoppo GJ;Saver JL;Jauch EC;Adams HP Jr;American Heart Association Stroke Council
中风协会理事会包括静脉注射重组组织纤溶酶原激活剂（rtPA）的具体建议。1尽管rtPA能有效改善神经系统结局，但大多数缺血性卒中患者并未接受rtPA治疗，主要是因为他们在目前批准的3小时给药时限后到达。增加治疗机会的一个潜在办法是指定一个较长的治疗时间窗。2-4最近的一项前瞻性研究，欧洲急性卒中合作研究（ECASS）-3，提供了关于rtPA（阿替普酶）治疗3-4.5小时窗口期的新数据。5.围绕这项研究的情况很重要。2002年，欧洲药品评价机构批准在症状发作后3小时内使用rtPA治疗缺血性卒中患者，条件是（1）完成症状发作后3小时窗口内使用rtPA的患者治疗经验的前瞻性登记研究（安全实施卒中溶栓监测研究，或SITS-MOST）6和（2）完成一项前瞻性、随机、安慰剂对照试验，在卒中发作后3至4.5小时内给予rtPA，ECASS-3。5使用特定方案的SITS-MOST报告称，rtPA后24小时症状性脑出血（根据SITS-MOST定义）的频率为1.7%（95%置信区间[CI] 1.4%至2.0%; Wahlgren等人6的图3）。rtPA后24小时，根据科克伦/国家神经疾病和卒中研究所（NINDS）定义的症状性脑出血的频率为7.3%（95% CI 6.7%-7.9%）。相比之下，在随机对照试验汇总数据中，该频率略低于8.6%（Wahlgren等人6的图2）。对于疗效，rtPA患者中90天时改良兰金量表评分为0、1和2的频率为54.8%（95% CI 53.5%-56.0%），与合并样本相当。6这些发现似乎证实了欧洲中心在3小时窗口内rtPA的潜在安全性。此外，安全实施脑卒中溶栓治疗-国际脑卒中治疗注册3至4.5小时研究（SITS-ISTR 3至4.5小时），对2002年12月至2007年11月期间从正在进行的国际登记系统中获得的有限数据进行事后抽样（SITS-ISTR），比较了11865例在症状发作3小时内接受rtPA治疗的患者与664例在3 - 4.5小时内接受治疗的患者。7大多数（72%）在3小时后接受治疗的患者在3至3.5小时之间接受治疗。尽管该研究存在一些缺陷，但在症状性脑出血、死亡率或90天时改良兰金量表评分（0 - 2分）方面，3-4.5小时队列与3小时队列之间无明显差异。7 SITS-ISTR是一项正在进行的登记研究，包括来自SITS-MOST、非欧洲中心和正在进行的研究的经验。美国心脏协会尽一切努力避免因外部关系或撰写小组成员的个人、专业或商业利益而可能产生的任何实际或潜在的利益冲突。具体而言，要求编写小组的所有成员填写并提交一份披露问卷，显示可能被视为真实的或潜在利益冲突的所有此类关系。该咨询于2009年4月22日获得美国心脏协会科学咨询和协调委员会的批准。个...
Association Stroke Council include specific recommendations for the administration of intravenous recombinant tissue plasminogen activator (rtPA). 1 Despite its effectiveness in improving neurological outcomes, the majority of patients with ischemic stroke are not treated with rtPA, largely because they arrive after the currently approved 3-hour time limit for administration of the medication. One of the potential approaches to increase treatment opportunities has been the designation of a longer time window for treatment. 2–4 A recent prospective study, the European Cooperative Acute Stroke Study (ECASS)-3, has provided new data on rtPA (alteplase) treatment in the 3-to-4.5–hour window. 5 The circumstances surrounding this study are important. In 2002, the European Medicines Evaluation Agency granted license for the use of rtPA for the treatment of ischemic stroke patients within 3 hours of symptom onset on condition of (1) the completion of a prospective registry of patient treatment experience with rtPA given within the 3-hour window from symptom onset (Safe Implementation of Thrombolysis in Stroke–Monitoring Study, or SITS-MOST) 6 and (2) the completion of a prospective, randomized, placebo-controlled trial of rtPA administered between 3 and 4.5 hours after stroke onset, ECASS-3. 5 SITS-MOST, which used a specified protocol, reported that the frequency of symptomatic intracerebral hemorrhage (per the SITS-MOST definition) at 24 hours after rtPA was 1.7%(95% confidence interval [CI] 1.4% to 2.0%; Figure 3 in Wahlgren et al6). The frequency of symptomatic intracerebral hemorrhage per the Cochrane/National Institute of Neurological Disorders and Stroke (NINDS) definition at 24 hours after rtPA was 7.3%(95% CI 6.7% to 7.9%). By comparison, this frequency was slightly less than 8.6% in data taken from a pool of randomized, controlled trials (Figure 2 in Wahlgren et al6). For efficacy, the frequency of scores of 0, 1, and 2 on the combined modified Rankin scale at 90 days was 54.8%(95% CI 53.5% to 56.0%) among rtPA patients, which was comparable to the pooled sample. 6 These findings appear to confirm the potential safety of rtPA within the 3-hour window in European centers. In addition, the Safe Implementation of Thrombolysis in Stroke–International Stroke Treatment Registry 3-to-4.5–hour study (SITS-ISTR 3-to-4.5 hour), a post hoc sampling of limited data acquired between December 2002 and November 2007 from the ongoing international registry (SITS-ISTR), compared 11 865 patients treated with rtPA within 3 hours of symptom onset with 664 patients who received treatment within 3 to 4.5 hours. 7 Most (72%) of the patients treated after 3 hours were treated between 3 and 3.5 hours. Although there were several weaknesses in that study, no differences between the 3-to-4.5–hour cohort and the 3-hour cohort were apparent with respect to symptomatic intracerebral hemorrhage, mortality, or modified Rankin Scale score of 0 to 2 at 90 days. 7 SITS-ISTR is an ongoing registry that includes experience from SITS-MOST, non-European centers, and active studies.The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This advisory was approved by the American Heart Association Science Advisory and Coordinating Committee on April 22, 2009. A …