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Comparative Study
. 2010 Nov 23:341:c6046.
doi: 10.1136/bmj.c6046.

Thrombolysis in very elderly people: controlled comparison of SITS International Stroke Thrombolysis Registry and Virtual International Stroke Trials Archive

Nishant K Mishra  1 , Niaz Ahmed, Grethe Andersen, José A Egido, Perttu J Lindsberg, Peter A Ringleb, Nils G Wahlgren, Kennedy R Lees; VISTA collaborators; SITS collaborators
Collaborators, Affiliations
Comparative Study

Thrombolysis in very elderly people: controlled comparison of SITS International Stroke Thrombolysis Registry and Virtual International Stroke Trials Archive

Nishant K Mishra et al. BMJ. .

Abstract

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.

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Conflict of interest statement

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.

Figures

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Fig 1 Description of analysed patients from two data sources
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Fig 2 Scores on modified Rankin scale (from 0=no symptoms from stroke to 6=death) at three months between patients who underwent thrombolysis with alteplase and controls, indicating shift towards improved outcomes with thrombolysis. Numbers within coloured cells are percentages
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Fig 3 Shift towards better outcomes on modified Rankin scale at three months adjusted for age and baseline severity (defined by National Institutes of Health stroke scale). Number of patients shown for age groups do not add up to 29 228 because numbers of patients ages <21 (n=38) and >100 (n=2) were too low to allow any comparison. All patients aged <21 were from SITS and underwent thrombolysis; 15 patients reached a 90 day modified Rankin score of 0, 10 patients attained a score of 1, eight patients reached a score of 2, one patient achieved a score of 3, and two a score of 4; two died. Two patients aged 101 did not undergo thrombolysis in VISTA neuroprotection trials; they achieved modified Rankin score of 0 and 4 at 90 days
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Fig 4 Odds ratios for score 0-1 on modified Rankin scale at three months adjusted for age and baseline National Institutes of Health stroke severity scale in patients who received thrombolytic therapy
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Fig 5 Odds ratios for score 0-2 on modified Rankin scale at three months adjusted for age and baseline National Institutes of Health stroke severity scale in patients who received thrombolytic therapy
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Fig 6 Odds ratios for mortality at three months adjusted for age and baseline National Institutes of Health stroke severity scale in patients who received thrombolytic therapy
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