Background/Purpose:Expert guidelines specify no upper age limit for alteplase for thrombolysis of acute ischemic stroke (AIS) but, until recently, European regulatory criteria restricted its use to patients aged 18 to 80 years. We performed pooled analyses of randomized controlled trial (RCT) and registry data to evaluate the benefit-risk profile of alteplase for AIS among patients aged >80 years to support a regulatory application to lift the upper age restriction.Methods:Individual patient data were evaluated from 7 randomized trials of alteplase (0.9 mg/kg) versus placebo or open control for AIS, and the European SITS-UTMOST registry database. Clinical outcomes, including good functional outcome (score 0–1, modified Rankin Scale day 90 or Oxford Handicap Score day 180), were evaluated in the full RCT and registry populations, and specified age-based subgroups (≤80 or >80 years) who met existing European regulatory criteria for alteplase, excluding upper age restriction.Results:Regardless of treatment allocation, 90-day mortality was lower among RCT patients aged ≤80 versus >80 years who otherwise met existing European regulatory criteria (246/2405 [10.2%] versus 307/1028 [29.9%], respectively). Among patients aged >80 years, alteplase versus placebo was associated with a higher proportion of good stroke outcome (modified Rankin Scale score 0–1; 99/518 [19.1%] versus 67/510 [13.1%]; P=0.0109) and similar 90-day mortality (153/518 [29.5%] versus 154/510 [30.2%]; P=0.8382). The odds of a good stroke outcome following alteplase allocation in the full RCT population were independent of age (P=0.7383). Good stroke outcome was reported for almost half (4821/11 169 [43.2%]) of the patients who received alteplase in routine practice. Outcomes in routine practice supported those achieved in RCTs.Conclusions:Alteplase for AIS has a positive benefit-risk profile among patients aged >80 years when administered according to other regulatory criteria. Alteplase for AIS should be evaluated on an individual benefit-risk basis.

中文翻译：

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阿替普酶用于80岁以上患者的急性缺血性卒中：个别患者数据的汇总分析。

背景/目的：专家指南未指定阿替普酶用于急性缺血性卒中（AIS）溶栓的年龄上限，但直到最近，欧洲监管标准仍将其使用限制在18至80岁的患者中。我们对随机对照试验（RCT）和注册数据进行了汇总分析，以评估80岁以上患者中阿替普酶治疗AIS的获益风险特征，以支持通过法规应用解除年龄上限限制。方法：评估了个体患者数据来自7项阿替普酶（0.9 mg / kg）相对于AIS的安慰剂或开放对照的随机试验，以及欧洲SITS-UTMOST注册数据库。临床结果，包括良好的功能结局（评分0-1，改良的兰金量表第90天或牛津残障评分第180天），已在全部RCT和注册人群中进行了评估，以及符合年龄的亚组（≤80或> 80岁）符合现行的阿替普酶欧洲法规标准，不包括年龄上限限制。结果：无论治疗方案如何，≤80的RCT患者的90天死亡率均低于> 80年，否则符合现有的欧洲法规标准（分别为246/2405 [10.2％]与307/1028 [29.9％]）。在80岁以上的患者中，阿替普酶和安慰剂的卒中预后良好比例更高（修订的兰金量表评分为0-1； 99/518 [19.1％]比67/510 [13.1％]；符合现有欧洲法规标准的80岁（分别为246/2405 [10.2％]与307/1028 [29.9％]）。在80岁以上的患者中，阿替普酶和安慰剂的卒中预后良好比例更高（修订的兰金量表评分为0-1； 99/518 [19.1％]比67/510 [13.1％]；符合现有欧洲法规标准的80岁（分别为246/2405 [10.2％]与307/1028 [29.9％]）。在80岁以上的患者中，阿替普酶和安慰剂的卒中预后良好比例更高（修订的兰金量表评分为0-1； 99/518 [19.1％]比67/510 [13.1％]；P = 0.0109）和类似的90天死亡率（153/518 [29.5％]与154/510 [30.2％]；P = 0.8382）。在所有RCT人群中，阿替普酶分配后良好卒中预后的几率与年龄无关（P = 0.7383）。在常规实践中，接受阿替普酶治疗的患者中有近一半（4821/11 169 [43.2％]）报告中风预后良好。常规实践的结果支持在RCT中获得的结论。结论：按照其他法规标准进行管理时，> 80岁的患者使用阿替普酶治疗AIS具有积极的获益风险。阿替普酶用于AIS的评估应以个人获益风险为基础。