Intravenous Thrombolysis in Patients With White Matter Hyperintensities in the WAKE-UP Trial
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Intravenous Thrombolysis in Patients With White Matter Hyperintensities in the WAKE-UP Trial. / Frey, Benedikt M; Shenas, Farhad; Boutitie, Florent; Cheng, Bastian; Cho, Tae-Hee; Ebinger, Martin; Endres, Matthias; Fiebach, Jochen B; Fiehler, Jens; Galinovic, Ivana; Barow, Ewgenia; Königsberg, Alina; Schlemm, Eckhard; Pedraza, Salvador; Lemmens, Robin; Thijs, Vincent; Muir, Keith W; Nighoghossian, Norbert; Simonsen, Claus Z; Gerloff, Christian; Thomalla, Götz; WAKE-UP Investigators.
in: STROKE, Jahrgang 54, Nr. 7, 07.2023, S. 1718-1725.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Intravenous Thrombolysis in Patients With White Matter Hyperintensities in the WAKE-UP Trial
AU - Frey, Benedikt M
AU - Shenas, Farhad
AU - Boutitie, Florent
AU - Cheng, Bastian
AU - Cho, Tae-Hee
AU - Ebinger, Martin
AU - Endres, Matthias
AU - Fiebach, Jochen B
AU - Fiehler, Jens
AU - Galinovic, Ivana
AU - Barow, Ewgenia
AU - Königsberg, Alina
AU - Schlemm, Eckhard
AU - Pedraza, Salvador
AU - Lemmens, Robin
AU - Thijs, Vincent
AU - Muir, Keith W
AU - Nighoghossian, Norbert
AU - Simonsen, Claus Z
AU - Gerloff, Christian
AU - Thomalla, Götz
AU - WAKE-UP Investigators
PY - 2023/7
Y1 - 2023/7
N2 - BACKGROUND: White matter hyperintensities of presumed vascular origin (WMH) are the most prominent imaging feature of cerebral small vessel disease (cSVD). Previous studies suggest a link between cSVD burden and intracerebral hemorrhage and worse functional outcome after thrombolysis in acute ischemic stroke. We aimed to determine the impact of WMH burden on efficacy and safety of thrombolysis in the MRI-based randomized controlled WAKE-UP trial of intravenous alteplase in unknown onset stroke.METHODS: The design of this post hoc study was an observational cohort design of a secondary analysis of a randomized trial. WMH volume was quantified on baseline fluid-attenuated inversion recovery images of patients randomized to either alteplase or placebo in the WAKE-UP trial. Excellent outcome was defined as score of 0-1 on the modified Rankin Scale after 90 days. Hemorrhagic transformation was assessed on follow-up imaging 24-36 hours after randomization. Treatment effect and safety were analyzed by fitting multivariable logistic regression models.RESULTS: Quality of scans was sufficient in 441 of 503 randomized patients to delineate WMH. Median age was 68 years, 151 patients were female, and 222 patients were assigned to receive alteplase. Median WMH volume was 11.4 mL. Independent from treatment, WMH burden was statistically significantly associated with worse functional outcome (odds ratio, 0.72 [95% CI, 0.57-0.92]), but not with higher chances of any hemorrhagic transformation (odds ratio, 0.78 [95% CI, 0.60-1.01]). There was no interaction of WMH burden and treatment group for the likelihood of excellent outcome (P=0.443) or any hemorrhagic transformation (P=0.151). In a subgroup of 166 patients with severe WMH, intravenous thrombolysis was associated with higher odds of excellent outcome (odds ratio, 2.40 [95% CI, 1.19-4.84]) with no significant increase in the rate of hemorrhagic transformation (odds ratio, 1.96 [95% CI, 0.80-4.81]).CONCLUSIONS: Although WMH burden is associated with worse functional outcome, there is no association with treatment effect or safety of intravenous thrombolysis in patients with ischemic stroke of unknown onset.REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifier: NCT01525290.
AB - BACKGROUND: White matter hyperintensities of presumed vascular origin (WMH) are the most prominent imaging feature of cerebral small vessel disease (cSVD). Previous studies suggest a link between cSVD burden and intracerebral hemorrhage and worse functional outcome after thrombolysis in acute ischemic stroke. We aimed to determine the impact of WMH burden on efficacy and safety of thrombolysis in the MRI-based randomized controlled WAKE-UP trial of intravenous alteplase in unknown onset stroke.METHODS: The design of this post hoc study was an observational cohort design of a secondary analysis of a randomized trial. WMH volume was quantified on baseline fluid-attenuated inversion recovery images of patients randomized to either alteplase or placebo in the WAKE-UP trial. Excellent outcome was defined as score of 0-1 on the modified Rankin Scale after 90 days. Hemorrhagic transformation was assessed on follow-up imaging 24-36 hours after randomization. Treatment effect and safety were analyzed by fitting multivariable logistic regression models.RESULTS: Quality of scans was sufficient in 441 of 503 randomized patients to delineate WMH. Median age was 68 years, 151 patients were female, and 222 patients were assigned to receive alteplase. Median WMH volume was 11.4 mL. Independent from treatment, WMH burden was statistically significantly associated with worse functional outcome (odds ratio, 0.72 [95% CI, 0.57-0.92]), but not with higher chances of any hemorrhagic transformation (odds ratio, 0.78 [95% CI, 0.60-1.01]). There was no interaction of WMH burden and treatment group for the likelihood of excellent outcome (P=0.443) or any hemorrhagic transformation (P=0.151). In a subgroup of 166 patients with severe WMH, intravenous thrombolysis was associated with higher odds of excellent outcome (odds ratio, 2.40 [95% CI, 1.19-4.84]) with no significant increase in the rate of hemorrhagic transformation (odds ratio, 1.96 [95% CI, 0.80-4.81]).CONCLUSIONS: Although WMH burden is associated with worse functional outcome, there is no association with treatment effect or safety of intravenous thrombolysis in patients with ischemic stroke of unknown onset.REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifier: NCT01525290.
U2 - 10.1161/STROKEAHA.122.040247
DO - 10.1161/STROKEAHA.122.040247
M3 - SCORING: Journal article
C2 - 37226772
VL - 54
SP - 1718
EP - 1725
JO - STROKE
JF - STROKE
SN - 0039-2499
IS - 7
ER -
