Thrombolysis in very elderly people: controlled comparison of SITS International Stroke Thrombolysis Registry and Virtual International Stroke Trials ArchiveBMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c6046 (Published 24 November 2010) Cite this as: BMJ 2010;341:c6046
- Nishant K Mishra, doctoral candidate1,
- Niaz Ahmed, neurologist2,
- Grethe Andersen, neurologist3,
- José A Egido, neurologist4,
- Perttu J Lindsberg, professor of applied neurology5,
- Peter A Ringleb, neurologist6,
- Nils G Wahlgren, professor of neurology2,
- Kennedy R Lees, professor of cerebrovascular medicine1
- for the VISTA and SITS collaborators
- 1Acute Stroke Unit, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow G11 6NT, UK
- 2Department of Neurology, Karolinska University Hospital, Karolinska Institutet 171 76 Stockholm, Sweden
- 3Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
- 4Department of Neurology, Hospital San Carlos, Spain
- 5Department of Neurology, Helsinki University Central Hospital, and Program of Molecular Neurology, University of Helsinki, Helsinki, Finland
- 6Department of Neurology, University Hospital of Heidelberg, Heidelberg, Germany
- Correspondence to: K R Lees
- Accepted 7 September 2010
Objective To assess effect of age on response to alteplase in acute ischaemic stroke.
Design Adjusted controlled comparison of outcomes between non-randomised patients who did or did not undergo thrombolysis. Analysis used Cochran-Mantel-Haenszel test and proportional odds logistic regression analysis.
Setting Collaboration between International Stroke Thrombolysis Registry (SITS-ISTR) and Virtual International Stroke Trials Archive (VISTA).
Participants 23 334 patients from SITS-ISTR (December 2002 to November 2009) who underwent thrombolysis and 6166 from VISTA neuroprotection trials (1998-2007) who did not undergo thrombolysis (as controls). Of the 29 500 patients (3472 aged >80 (“elderly,” mean 84.6), data on 272 patients were missing for baseline National Institutes of Health stroke severity score, leaving 29 228 patients for analysis adjusted for age and baseline severity.
Main outcome measures Functional outcomes at 90 days measured by score on modified Rankin scale.
Results Median severity at baseline was the same for patients who underwent thrombolysis and controls (median baseline stroke scale score: 12 for each group, P=0.14; n=29 228). The distribution of scores on the modified Rankin scale was better among all thrombolysis patients than controls (odds ratio 1.6, 95% confidence interval 1.5 to 1.7; Cochran-Mantel-Haenszel P<0.001). The association occurred independently among patients aged ≤80 (1.6, 1.5 to 1.7; P<0.001; n=25 789) and in those aged >80 (1.4, 1.3 to 1.6; P<0.001; n=3439). Odds ratios were consistent across all 10 year age ranges above 30, and benefit was significant from age 41 to 90; dichotomised outcomes (score on modified Rankin scale 0-1 v 2-6; 0-2 v 3-6; and 6 (death) v rest) were consistent with the results of the ordinal analysis.
Conclusions Outcome in patients with acute ischaemic stroke is significantly better in those who undergo thrombolysis compared with those who do not. Increasing age is associated with poorer outcome but the association between thrombolysis treatment and improved outcome is maintained in very elderly people. Age alone should not be a barrier to treatment.
The SITS steering committee members were A Davalos, M Grond, G Ford, W Hacke, M Hennerici, M Kaste, V Larrue, KR Lees, RO Roine, D Toni, and N Wahlgren . The VISTA steering committee members were A Alexandrov, PW Bath, E Bluhmki, L Claesson, J Curram, SM Davis, G Donnan, HC Diener, M Fisher, B Gregson, J Grotta, W Hacke, MG Hennerici, M Hommel, M Kaste, KR Lees (chair), P Lyden, J Marler, K Muir, R Sacco, A Shuaib, P Teal, NG Wahlgren, S Warach, and C Weimar. The data were presented by NKM at the European Stroke Conference, 2010. The analyses were based on a research proposal approved both by the VISTA steering committee and the SITS-ISTR.
Contributors: NKM, NGW, and NA had access to the SITS-ISTR data. NKM and KRL had access to the VISTA data. NKM and KRL designed and interpreted the analyses and drafted the manuscript. NGW, NA, GA, JEH, PJL, and PAR contributed SITS-ISTR data, reviewed the outline proposal, commented on the manuscript, and approved the final version. All authors take full responsibility for the content. The manuscript was reviewed and approved by the steering committees of VISTA and SITS. No commercial organisation was involved in the origination, execution or reporting of this work. NKM is guarantor.
Funding: VISTA has received financial support from the European Stroke Organisation in the form of an unrestricted grant and contributions towards data extraction and capacity building from the Universities of Glasgow, California San Diego, Nottingham, Edmonton, Calgary, Texas, and Massachusetts; from commercial groups including Brainsgate, Novartis, Boehringer Ingelheim, and the Vertical Group; and from grant agencies and charities including the UK Stroke Association. SITS-ISTR is funded by an unrestricted grant from Boehringer Ingelheim, Ferrer, and a grant from European Union Public Health Executive Authority (PHEA). Financial support was also provided through the regional agreement on medical training and research (ALF) between Stockholm County Council and the Karolinska Institute. NKM is supported by a Scottish Overseas Research Studentship, a University of Glasgow scholarship, and an educational grant from the European Stroke Organisation for Young Neurologists. PJL is supported by the Finnish Academy and Sigrid Juselius foundation and Helsinki University Hospital research funds (EVO).
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: KRL has received honorariums from Boehringer Ingelheim, Lundbeck, Thrombogenics, Talecris. GA is a member of the advisory board for Boehringer Ingelheim, Denmark. JAE was investigator of ECASS II, ECASS III, and PROFESS promoted by Boehringer Ingelheim. NA is an employee of SITS International, which received a grant from Boehringer Ingelheim for the SITS-MOST/SITS-ISTR study with alteplase. NGW has received expenses from Boehringer Ingelheim for his role as member of the steering committee in relation to the ECASS III trial with alteplase and served as a consultant to Thrombogenics as chairman of the DSMB. SITS International (chaired by NGW) received a grant from Boehringer Ingelheim and from Ferrer for the SITS-MOST/SITS-ISTR. His institution has also received grant support towards administrative expenses for coordination of the ECASS III trial. NGW has also received lecture fees from Boehringer Ingelheim and from Ferrer. PAR is the German deputy national SITS coordinator. He was investigator of ECASS III and PROFESS sponsored by Boehringer Ingelheim and of DIAS and DIAS-2 sponsored by PAION. He received honorariums and travel expenses from Boehringer Ingelheim, PAION, and Ferrer.
Ethical approval: Not required.
Data sharing: Data sharing: no additional data available.
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