Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian Alteplase for Stroke Effectiveness Study

P N Sylaja; Robert Cote; Alastair M Buchan; Michael D Hill

doi:10.1136/jnnp.2005.086595

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Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian Alteplase for Stroke Effectiveness Study

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Thrombolysis for acute stroke: what about the actual impact of patients older than 80 years?
Giovanni Orlandi
Published on: 13 April 2016
Risk and benefit of tPA in elderly ischemic stroke patients
John M Reid
Published on: 13 April 2016

Published on: 13 April 2016
Thrombolysis for acute stroke: what about the actual impact of patients older than 80 years?
- Giovanni Orlandi, Neurologist
- Other Contributors:
  Alberto Chiti, Simona Fanucchi, Simone Gallerini, Chiara Sonnoli and Nicola Morelli.
Dear Editor,
We read with great interest the study by Sylaja et al. [1] evaluating the clinical characteristics and complications and the predictors of outcome after intravenous tPA treatment in patients aged >/= 80 years. The authors found that age >/= 80 years was an independent predictor of outcome, but it was not associated with an increased risk of symptomatic intracerebral haemorrhage. Taking into acc...
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Dear Editor,
We read with great interest the study by Sylaja et al. [1] evaluating the clinical characteristics and complications and the predictors of outcome after intravenous tPA treatment in patients aged >/= 80 years. The authors found that age >/= 80 years was an independent predictor of outcome, but it was not associated with an increased risk of symptomatic intracerebral haemorrhage. Taking into account that the natural history of stroke leads to a less favourable outcome with advancing age, it doesn’t seem justified to withold an effective therapy like thrombolysis because of age alone [2]. Thus the elderly could benefit from thrombolysis, but what would their actual impact in clinical practice be? Basing on Canadian Alteplase for Stroke Effectiveness Study, Sylaja et al. [1] report that 270/1135 (23.8%) treated patients are aged >/= 80 years. However, this relevant proportion represents only a part of the elderly stroke patients.
To elucidate this issue, we retrospectively reviewed data from patients admitted to our hospital for acute stroke in 2005. 258 patients (median age 71 years, range 19-97, 62/258-24.0% with age >80 years) were admitted, but only 102/258 (39.5%) arrived within three hours from stroke onset and in 72/102 (70.6%) cranial computed tomography didn’t show haemorrhage or neoplasm. 21/72 (29.2%) had >80 years (median age 84 years, range 81-90) and nobody of them was treated according to SITS-MOST selection criteria which prevent thrombolysis in the elderly. However, only 7/21 (33.3%) didn’t present other defined exclusion criteria (minor neurological deficit or symptoms rapidly improving before start of infusion in 2/21-9.5%; severe stroke in 7/21-33.3%; prior stroke within the previous 3 months in 2/21-9.5%; major surgery in previous 3 months in 1/21-4.8%; oral anticoagulant treatment with INR >1.7 in 1/21-4.8%; arrival at the border of the three hours time window in 1/21-4.8%). These patients (median age 85.6 years, range 82-90; median NIHSS at admission 15.7, range 8-24) had a median hospital stay of 22.7 days (range 12-35) and were all disabled at discharge (median mRS at discharge 3.9, range 3-5 vs median mRS at admission 2.4, range 2-3). Both hospital stay lenght [3] and disability rate [4] could have probably been reduced by thrombolysis.
Basing on our data, we can estimate that about one third of patients aged >80 years with ischaemic stroke arriving at hospital within three hours from stroke onset could be treated, that is 7/62 (11.3%) of the elderly stroke patients. Our data confirm that tPA treatment should be implementated also in carefully selected elderly patients.
References
1. Sylaja PN, Cote R, Buchan AM, et al. Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian Alteplase for Stroke Effectiveness Study. J Neurol Neurosurg Psychiatry 2006;77:826-9.
2. Schwark C, Schellinger PD. Is old age really a reason to withhold thrombolytic therapy? J Neurol Neurosurg Psychiatry 2006;77:289.
3. Saposnik G, Di Legge S, Webster F, Hachinski V. Predictors of major neurologic improvement after thrombolysis in acute stroke. Neurology 2005;65:1169-74.
4. Hacke W, Donnan G, et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004;363:768-74.
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Conflict of Interest:
None declared.
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Published on: 13 April 2016
Risk and benefit of tPA in elderly ischemic stroke patients
- John M Reid, Neurologist
- Other Contributors:
  Gordon J Gubitz, and Stephen J Phillips.
Dear Editor,
In the recent article by Sylaja et al [1] patients from the Canadian Alteplase for Stroke Effectiveness Study [2] treated with tPA aged >/= 80 years had a symptomatic intracranial haemorrhage (SICH) rate of 4.4% compared to 4.6% in patients <80 years old. These data are encouraging. The authors mention patient selection bias may be a factor in their results, however we wonder whether there may...
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Dear Editor,
In the recent article by Sylaja et al [1] patients from the Canadian Alteplase for Stroke Effectiveness Study [2] treated with tPA aged >/= 80 years had a symptomatic intracranial haemorrhage (SICH) rate of 4.4% compared to 4.6% in patients <80 years old. These data are encouraging. The authors mention patient selection bias may be a factor in their results, however we wonder whether there may be reporting bias also. CASES [2] was a study of voluntary reporting of tPA-treated ischemic stroke patients across Canada over a 2.5 year period. As there was no mandatory reporting it is conceivable that centres with poor outcomes or a high rate of SICH would have avoided reporting their experience with tPA. Finally, although the 3 month outcomes appear encouraging, there was no control group for comparison, so the balance of risk and benefit of t-PA in this age group remains unclear.
In our own hospital, 20 % (34/170) of tPA-treated patients over the last 10 years are aged >/= 80 years. We have observed no age difference between patients with and without SICH following tPA (mean age [¡Àstandard deviation] 70+/-12 vs.70+/-13 years, p=0.95). However, as Sylaja et al note [1] there is heterogeneity in the reports of SICH in tPA-treated elderly stroke patients, and a link between age and intracerebral hemorrhage in thrombolysis for myocardial ischaemia is established. A large post-marketing study of tPA use showed age was an independent predictor of SICH (odds ratio of 1.32, 95% confidence interval 1.03-1.60 per 10 years, [3]).
We hope that further randomised evidence will reduce this uncertainty. The authors [1] highlight the Third International Stroke Trial (IST-3). To date, this is the only ongoing randomized study enrolling patients aged over 80; more than 180 patients >/= 80 years had been recruited by May 2006 (European Stroke Conference, ongoing trials poster), thereby already increasing the randomised evidence for patients aged >/= 80 (currently only n=42, [4]) more than 4-fold. Further information about the IST-3 is available at www.IST3.com.
John M Reid, Gordon J Gubitz and Stephen J Phillips.
Halifax Infirmary, Queen Elizabeth Sciences Centre, Nova Scotia, Canada.
Competing interest: Dr Reid has received funding from an unrestricted educational grant from Hoffmann-LaRoche.
References
1. Sylaja PN, Cote R, Buchan AM, Hill MD; Canadian Alteplase for Stroke Effectiveness Study (CASES) Investigators. Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian Alteplase for Stroke Effectiveness Study. J Neurol Neurosurg Psychiatry. 2006;77:826-9.
2. Hill MD, Buchan AM; Canadian Alteplase for Stroke Effectiveness Study (CASES) Investigators. Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study. CMAJ. 2005;172:1307 -12.
3. Tanne D, Kasner SE, Demchuk AM, Koren-Morag N, Hanson S, Grond M, Levine SR. Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey. Circulation. 2002;105:1679-85.
4. Wardlaw JM, del Zoppo G, Yamaguchi T, Berge E. Thrombolysis for acute ischaemic stroke. The Cochrane Database of Systematic Reviews 2003, Issue 3. Art. No.: CD000213. DOI: 10.1002/14651858.CD000213.
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Conflict of Interest:
None declared.
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