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Extending thrombolysis to 4·5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data.

Artikel i vetenskaplig tidskrift
Författare Bruce C V Campbell
Henry Ma
Peter A Ringleb
Mark W Parsons
Leonid Churilov
Martin Bendszus
Christopher R Levi
Chung Hsu
Timothy J Kleinig
Marc Fatar
Didier Leys
Carlos Molina
Tissa Wijeratne
Sami Curtze
Helen M Dewey
P Alan Barber
Kenneth S Butcher
Deidre A De Silva
Christopher F Bladin
Nawaf Yassi
Johannes A R Pfaff
Gagan Sharma
Andrew Bivard
Patricia M Desmond
Stefan Schwab
Peter D Schellinger
Bernard Yan
Peter J Mitchell
Joaquín Serena
Danilo Toni
Vincent Thijs
Werner Hacke
Stephen M Davis
Geoffrey A Donnan
Turgut Tatlisumak
Publicerad i Lancet (London, England)
Volym 394
Nummer/häfte 10193
Sidor 139-147
ISSN 1474-547X
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap
Sidor 139-147
Språk en
Länkar dx.doi.org/10.1016/S0140-6736(19)31...
Ämnesord Brain Ischemia, diagnostic imaging, drug therapy, Cerebral Hemorrhage, chemically induced, Diffusion Magnetic Resonance Imaging, Fibrinolytic Agents, adverse effects, therapeutic use, Humans, Perfusion Imaging, Stroke, diagnostic imaging, drug therapy, Thrombolytic Therapy, methods, Time-to-Treatment, Tissue Plasminogen Activator, adverse effects, therapeutic use, Tomography, X-Ray Computed, Treatment Outcome
Ämneskategorier Neurologi


Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036.We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66).Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.None.

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