TY - JOUR
T1 - Time to Treatment With Intravenous Thrombolysis Before Thrombectomy and Functional Outcomes in Acute Ischemic Stroke A Meta-Analysis
AU - Kaesmacher, Johannes
AU - Cavalcante, Fabiano
AU - Kappelhof, Manon
AU - Treurniet, Kilian M.
AU - Rinkel, Leon
AU - Liu, Jianmin
AU - Yan, Bernard
AU - Zi, Wenjie
AU - Kimura, Kazumi
AU - Eker, Omer F.
AU - Zhang, Yongwei
AU - Piechowiak, Eike I.
AU - van Zwam, Wim
AU - Liu, Sheng
AU - Strbian, Daniel
AU - Uyttenboogaart, Maarten
AU - Dobrocky, Tomas
AU - Miao, Zhongrong
AU - Suzuki, Kentaro
AU - Zhang, Lei
AU - van Oostenbrugge, Robert
AU - Meinel, Thomas R.
AU - Guo, Changwei
AU - Seiffge, David
AU - Yin, Congguo
AU - Bütikofer, Lukas
AU - Lingsma, Hester
AU - Nieboer, Daan
AU - Yang, Pengfei
AU - Mitchell, Peter
AU - Majoie, Charles
AU - IRIS collaborators
AU - Fischer, Urs
AU - Roos, Yvo
AU - Gralla, Jan
N1 - Publisher Copyright: © 2024 American Medical Association.
PY - 2024/3/5
Y1 - 2024/3/5
N2 - 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. Enrollmentwas 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 occlusionwere 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 IVTwas 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). Therewas 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 differencewas9%(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 thrombectomywas 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.
AB - 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. Enrollmentwas 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 occlusionwere 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 IVTwas 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). Therewas 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 differencewas9%(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 thrombectomywas 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.
UR - http://www.scopus.com/inward/record.url?scp=85184800497&partnerID=8YFLogxK
U2 - 10.1001/jama.2024.0589
DO - 10.1001/jama.2024.0589
M3 - Article
C2 - 38324409
SN - 0098-7484
VL - 331
SP - 764
EP - 777
JO - JAMA
JF - JAMA
IS - 9
ER -