학술논문

Time to Treatment With Intravenous Thrombolysis Before Thrombectomy and Functional Outcomes in Acute Ischemic Stroke: A Meta-Analysis.
Document Type
Article
Source
JAMA: Journal of the American Medical Association. 3/5/2024, Vol. 331 Issue 9, p764-777. 14p.
Subject
*ISCHEMIC stroke
*THROMBECTOMY
*THROMBOLYTIC therapy
*STROKE patients
*FUNCTIONAL status
Language
ISSN
0098-7484
Abstract
Key Points: Question: In patients with acute ischemic stroke undergoing thrombectomy, does a potential benefit associated with intravenous thrombolysis vary according to treatment times? Findings: In this individual participant data meta-analysis (n = 2313) of 6 randomized clinical trials, intravenous thrombolysis plus thrombectomy was significantly associated with a favorable shift in functional outcome at 90 days vs thrombectomy alone if the time from symptom onset to expected administration of intravenous thrombolysis was within 2 hours 20 minutes. Thereafter, there was no statistically significant association. Meaning: The findings indicate that the benefit associated with intravenous thrombolysis prior to thrombectomy was time dependent and lessened with longer times between symptom onset and expected administration of intravenous thrombolysis. Importance: The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for IVT followed by thrombectomy. Objective: To determine whether the benefit associated with IVT plus thrombectomy vs thrombectomy alone decreases with treatment time from symptom onset. Design, Setting, and Participants: Individual participant data meta-analysis from 6 randomized clinical trials comparing IVT plus thrombectomy vs thrombectomy alone. Enrollment was between January 2017 and July 2021 at 190 sites in 15 countries. All participants were eligible for IVT and thrombectomy and presented directly at thrombectomy-capable stroke centers (n = 2334). For this meta-analysis, only patients with an anterior circulation large-vessel occlusion were included (n = 2313). Exposure: Interval from stroke symptom onset to expected administration of IVT and treatment with IVT plus thrombectomy vs thrombectomy alone. Main Outcomes and Measures: The primary outcome analysis tested whether the association between the allocated treatment (IVT plus thrombectomy vs thrombectomy alone) and disability at 90 days (7-level modified Rankin Scale [mRS] score range, 0 [no symptoms] to 6 [death]; minimal clinically important difference for the rates of mRS scores of 0-2: 1.3%) varied with times from symptom onset to expected administration of IVT. Results: In 2313 participants (1160 in IVT plus thrombectomy group vs 1153 in thrombectomy alone group; median age, 71 [IQR, 62 to 78] years; 44.3% were female), the median time from symptom onset to expected administration of IVT was 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). There was a statistically significant interaction between the time from symptom onset to expected administration of IVT and the association of allocated treatment with functional outcomes (ratio of adjusted common odds ratio [OR] per 1-hour delay, 0.84 [95% CI, 0.72 to 0.97], P =.02 for interaction). The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT (adjusted common OR for a 1-step mRS score shift toward improvement, 1.49 [95% CI, 1.13 to 1.96] at 1 hour, 1.25 [95% CI, 1.04 to 1.49] at 2 hours, and 1.04 [95% CI, 0.88 to 1.23] at 3 hours). For a mRS score of 0, 1, or 2, the predicted absolute risk difference was 9% (95% CI, 3% to 16%) at 1 hour, 5% (95% CI, 1% to 9%) at 2 hours, and 1% (95% CI, −3% to 5%) at 3 hours. After 2 hours 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant and the point estimate crossed the null association at 3 hours 14 minutes. Conclusions and Relevance: In patients presenting at thrombectomy-capable stroke centers, the benefit associated with IVT plus thrombectomy vs thrombectomy alone was time dependent and statistically significant only if the time from symptom onset to expected administration of IVT was short. This individual participant data meta-analysis assesses treatment time from stroke symptom onset and disability level after treatment with intravenous thrombolysis plus thrombectomy vs thrombectomy alone among patients who presented directly at thrombectomy-capable stroke centers. [ABSTRACT FROM AUTHOR]