Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
JAMA. 2013 Jun 19;309(23):2480-8. doi: 10.1001/jama.2013.6959.
Randomized clinical trials suggest the benefit of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke is time dependent. However, modest sample sizes have limited characterization of the extent to which onset to treatment (OTT) time influences outcome; and the generalizability of findings to clinical practice is uncertain.
To evaluate the degree to which OTT time is associated with outcome among patients with acute ischemic stroke treated with intraveneous tPA.
DESIGN, SETTING, AND PATIENTS: Data were analyzed from 58,353 patients with acute ischemic stroke treated with tPA within 4.5 hours of symptom onset in 1395 hospitals participating in the Get With The Guidelines-Stroke Program, April 2003 to March 2012.
Relationship between OTT time and in-hospital mortality, symptomatic intracranial hemorrhage, ambulatory status at discharge, and discharge destination.
Among the 58,353 tPA-treated patients, median age was 72 years, 50.3% were women, median OTT time was 144 minutes (interquartile range, 115-170), 9.3% (5404) had OTT time of 0 to 90 minutes, 77.2% (45,029) had OTT time of 91 to 180 minutes, and 13.6% (7920) had OTT time of 181 to 270 minutes. Median pretreatment National Institutes of Health Stroke Scale documented in 87.7% of patients was 11 (interquartile range, 6-17). Patient factors most strongly associated with shorter OTT included greater stroke severity (odds ratio [OR], 2.8; 95% CI, 2.5-3.1 per 5-point increase), arrival by ambulance (OR, 5.9; 95% CI, 4.5-7.3), and arrival during regular hours (OR, 4.6; 95% CI, 3.8-5.4). Overall, there were 5142 (8.8%) in-hospital deaths, 2873 (4.9%) patients had intracranial hemorrhage, 19,491 (33.4%) patients achieved independent ambulation at hospital discharge, and 22,541 (38.6%) patients were discharged to home. Faster OTT, in 15-minute increments, was associated with reduced in-hospital mortality (OR, 0.96; 95% CI, 0.95-0.98; P < .001), reduced symptomatic intracranial hemorrhage (OR, 0.96; 95% CI, 0.95-0.98; P < .001), increased achievement of independent ambulation at discharge (OR, 1.04; 95% CI, 1.03-1.05; P < .001), and increased discharge to home (OR, 1.03; 95% CI, 1.02-1.04; P < .001).
In a registry representing US clinical practice, earlier thrombolytic treatment was associated with reduced mortality and symptomatic intracranial hemorrhage, and higher rates of independent ambulation at discharge and discharge to home following acute ischemic stroke. These findings support intensive efforts to accelerate hospital presentation and thrombolytic treatment in patients with stroke.
重要性：随机临床试验表明，静脉内组织型纤溶酶原激活剂（tPA）在急性缺血性脑卒中中的益处与时间有关。然而，适度的样本量限制了对起始至治疗时间（OTT）时间影响结果的程度的特征描述；并且发现结果对临床实践的推广性是不确定的。
目的：评估急性缺血性脑卒中患者接受静脉内 tPA 治疗时，OTT 时间与结局的关联程度。
设计、地点和患者：对 2003 年 4 月至 2012 年 3 月期间在参与 Get With The Guidelines-Stroke 计划的 1395 家医院接受 tPA 治疗且症状发作后 4.5 小时内的 58353 名急性缺血性脑卒中患者的数据进行了分析。
主要结局和措施：OTT 时间与住院死亡率、症状性颅内出血、出院时的活动状态以及出院去向之间的关系。
结果：在接受 tPA 治疗的 58353 名患者中，中位年龄为 72 岁，50.3%为女性，中位 OTT 时间为 144 分钟（四分位距，115-170），9.3%（5404）OTT 时间为 0 至 90 分钟，77.2%（45029）OTT 时间为 91 至 180 分钟，13.6%（7920）OTT 时间为 181 至 270 分钟。在 87.7%的患者中，入院前接受了国立卫生研究院卒中量表评估，中位数为 11 分（四分位距，6-17）。与较短 OTT 时间相关的患者因素主要包括更严重的卒中严重程度（比值比[OR]，2.8；95%置信区间[CI]，每增加 5 分，2.5-3.1）、乘坐救护车到达（OR，5.9；95%CI，4.5-7.3）和在正常工作时间到达（OR，4.6；95%CI，3.8-5.4）。总的来说，5142 名（8.8%）患者在院内死亡，2873 名（4.9%）患者发生颅内出血，19491 名（33.4%）患者在出院时能够独立行走，22541 名（38.6%）患者出院回家。OTT 每增加 15 分钟，与住院死亡率降低相关（OR，0.96；95%CI，0.95-0.98；P <.001），症状性颅内出血减少（OR，0.96；95%CI，0.95-0.98；P <.001），出院时实现独立活动的比例增加（OR，1.04；95%CI，1.03-1.05；P <.001），出院回家的比例增加（OR，1.03；95%CI，1.02-1.04；P <.001）。
结论和相关性：在代表美国临床实践的登记处中，更早的溶栓治疗与降低死亡率和症状性颅内出血相关，与急性缺血性脑卒中后出院时实现独立活动和出院回家的比例增加相关。这些发现支持在患者中积极努力加快入院和溶栓治疗。
