Department of Neurology, Cerebrovascular Center, Neurological Institute, Cleveland Clinic, OH (S.M., K.U., M.S.H.).
Duke Clinical Research Institute, Duke University, Durham, NC (N.S., B.A.).
Circulation. 2023 Jul 4;148(1):20-34. doi: 10.1161/CIRCULATIONAHA.123.064053. Epub 2023 May 18.
Existing data and clinical trials could not determine whether faster intravenous thrombolytic therapy (IVT) translates into better long-term functional outcomes after acute ischemic stroke among those treated with endovascular thrombectomy (EVT). Patient-level national data can provide the required large population to study the associations between earlier IVT, versus later, with longitudinal functional outcomes and mortality in patients receiving IVT+EVT combined treatment.
This cohort study included older US patients (age ≥65 years) who received IVT within 4.5 hours or EVT within 7 hours after acute ischemic stroke using the linked 2015 to 2018 Get With The Guidelines-Stroke and Medicare database (38 913 treated with IVT only and 3946 with IVT+EVT). Primary outcome was home time, a patient-prioritized functional outcome. Secondary outcomes included all-cause mortality in 1 year. Multivariate logistic regression and Cox proportional hazards models were used to evaluate the associations between door-to-needle (DTN) times and outcomes.
Among patients treated with IVT+EVT, after adjusting for patient and hospital factors, including onset-to-EVT times, each 15-minute increase in DTN times for IVT was associated with significantly higher odds of zero home time in a year (never discharged to home) (adjusted odds ratio, 1.12 [95% CI, 1.06-1.19]), less home time among those discharged to home (adjusted odds ratio, 0.93 per 1% of 365 days [95% CI, 0.89-0.98]), and higher all-cause mortality (adjusted hazard ratio, 1.07 [95% CI, 1.02-1.11]). These associations were also statistically significant among patients treated with IVT but at a modest degree (adjusted odds ratio, 1.04 for zero home time, 0.96 per 1% home time for those discharged to home, and adjusted hazard ratio 1.03 for mortality). In the secondary analysis where the IVT+EVT group was compared with 3704 patients treated with EVT only, shorter DTN times (≤60, 45, and 30 minutes) achieved incrementally more home time in a year, and more modified Rankin Scale 0 to 2 at discharge (22.3%, 23.4%, and 25.0%, respectively) versus EVT only (16.4%, <0.001 for each). The benefit dissipated with DTN>60 minutes.
Among older patients with stroke treated with either IVT only or IVT+EVT, shorter DTN times are associated with better long-term functional outcomes and lower mortality. These findings support further efforts to accelerate thrombolytic administration in all eligible patients, including EVT candidates.
现有的数据和临床试验无法确定对于接受血管内血栓切除术(EVT)治疗的急性缺血性中风患者,更快的静脉溶栓治疗(IVT)是否能转化为更好的长期功能结局。患者水平的全国数据可以提供所需的大量人群,以研究更早的 IVT 与更晚的 IVT 与接受 IVT+EVT 联合治疗的患者的纵向功能结局和死亡率之间的关联。
这项队列研究纳入了使用 2015 至 2018 年 Get With The Guidelines-Stroke 和 Medicare 数据库(38913 例仅接受 IVT 治疗和 3946 例接受 IVT+EVT 治疗的年龄≥65 岁的美国老年患者)。主要结局是居家时间,这是一个患者优先的功能结局。次要结局包括 1 年内的全因死亡率。多变量逻辑回归和 Cox 比例风险模型用于评估门到针(DTN)时间与结局之间的关联。
在接受 IVT+EVT 治疗的患者中,在校正患者和医院因素后,包括发病到 EVT 的时间,IVT 的 DTN 每增加 15 分钟,与 1 年内零居家时间(从未出院回家)的几率显著增加相关(校正比值比,1.12 [95%CI,1.06-1.19]),出院回家的患者居家时间减少(校正比值比,每 365 天 1%的居家时间减少 0.93 [95%CI,0.89-0.98]),全因死亡率升高(校正风险比,1.07 [95%CI,1.02-1.11])。在仅接受 IVT 治疗的患者中,这些关联也具有统计学意义,但程度较轻(校正比值比,零居家时间为 1.04,出院回家患者居家时间每 1%为 0.96,死亡率为 1.03)。在将 IVT+EVT 组与仅接受 EVT 治疗的 3704 例患者进行的二次分析中,较短的 DTN 时间(≤60、45 和 30 分钟)使 1 年内的居家时间逐渐增加,出院时的改良 Rankin 量表评分 0 至 2 分的比例也更高(分别为 22.3%、23.4%和 25.0%,均为 EVT 治疗组的 16.4%,<0.001)。超过 60 分钟的 DTN 时间会降低获益。
在接受 IVT 或 IVT+EVT 治疗的老年卒中患者中,较短的 DTN 时间与更好的长期功能结局和更低的死亡率相关。这些发现支持进一步努力加快所有符合条件的患者(包括 EVT 候选者)的溶栓治疗。