Show simple item record

dc.contributor.authorLees, KR
dc.contributor.authorBluhmki, E
dc.contributor.authorvon Kummer, R
dc.contributor.authorBrott, TG
dc.contributor.authorToni, D
dc.contributor.authorGrotta, JC
dc.contributor.authorAlbers, GW
dc.contributor.authorKaste, M
dc.contributor.authorMarler, JR
dc.contributor.authorHamilton, SA
dc.contributor.authorTilley, BC
dc.contributor.authorDavis, SM
dc.contributor.authorDonnan, GA
dc.contributor.authorHacke, W
dc.contributor.authorNinds, EA
dc.date.available2014-05-21T22:00:09Z
dc.date.issued2010-05-15
dc.identifierpii: S0140-6736(10)60491-6
dc.identifier.citationLees, K. R., Bluhmki, E., von Kummer, R., Brott, T. G., Toni, D., Grotta, J. C., Albers, G. W., Kaste, M., Marler, J. R., Hamilton, S. A., Tilley, B. C., Davis, S. M., Donnan, G. A., Hacke, W. & Ninds, E. A. (2010). Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. LANCET, 375 (9727), pp.1695-1703. https://doi.org/10.1016/S0140-6736(10)60491-6.
dc.identifier.issn0140-6736
dc.identifier.urihttp://hdl.handle.net/11343/28747
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractBACKGROUND: Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis. METHODS: We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis. FINDINGS: Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min. INTERPRETATION: Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit. FUNDING: None.
dc.languageEnglish
dc.publisherELSEVIER SCIENCE INC
dc.subjectNeurology and Neuromuscular Diseases; Clinical Health (Organs
dc.subjectDiseases and Abnormal Conditions) not elsewhere classified
dc.titleTime to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials
dc.typeJournal Article
dc.identifier.doi10.1016/S0140-6736(10)60491-6
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentMedicine - Royal Melbourne Hospital
melbourne.source.titleLANCET
melbourne.source.volume375
melbourne.source.issue9727
melbourne.source.pages1695-1703
melbourne.publicationid145622
melbourne.elementsid323183
melbourne.contributor.authorDonnan, Geoffrey
melbourne.contributor.authorDavis, Stephen
melbourne.contributor.authorParsons, Mark
dc.identifier.eissn1474-547X
melbourne.fieldofresearch320905 Neurology and neuromuscular diseases
melbourne.seocode200199 Clinical health not elsewhere classified
melbourne.accessrightsThis item is currently not available from this repository


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record