Influence of Age on Outcome From Thrombolysis in Acute Stroke: A Controlled Comparison in Patients From the Virtual International Stroke Trials Archive (VISTA)

Background and Purpose— Thrombolysis for acute ischemic stroke in patients aged >80 years is not approved in some countries due to limited trial data in the very elderly. We compared outcomes between thrombolysed and nonthrombolysed (control) patients from neuroprotection trials to assess any influence of age on response. Method— Among patients with ischemic stroke of known age, pretreatment severity (baseline National Institutes of Health Scale Score), and 90-day outcome (modified Rankin Scale score; National Institutes of Health Scale score), we compared the distribution of modified Rankin score in thrombolysed patients with control subjects by Cochran-Mantel-Haenszel test and then logistic regression after adjustment for age and baseline National Institutes of Health Scale score. We examined patients ≤80 and ≥81 years separately and then each age decile. Results— Rankin data were available for 5817 patients, 1585 thrombolysed and 4232 control subjects; 20.5% were aged >80 years (mean±SD, 85.1±3.4 years). Baseline severity was higher among thrombolysed than control subjects (median National Institutes of Health Scale score 14 versus 13, P<0.05). The distribution of modified Rankin Scale scores was better among thrombolysed patients (P<0.0001; OR, 1.39; 95% CI, 1.26 to 1.54). The association occurred independently with similar magnitude among young (P<0.0001; OR, 1.42; 95% CI, 1.26 to 1.59) and elderly (P=0.002; OR, 1.34; 95% CI, 1.05 to 1.70) patients. ORs were consistent across all age deciles >30 years; outcomes assessed by National Institutes of Health Scale score gave supporting significant findings, and dichotomized modified Rankin Scale score outcomes were also consistent. Conclusions— Outcome after thrombolysis for acute ischemic stroke was significantly better than in control subjects. Despite the expected poorer outcomes among elderly compared with young patients that is independent of any treatment effect, the association between thrombolysis treatment and improved outcome is maintained in the very elderly. Age alone should not be a barrier to treatment.

[1]  M. Kaste,et al.  The European Cooperative Acute Stroke Study (ECASS) , 1993 .

[2]  Nirds,et al.  Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group , 1995 .

[3]  Joseph P. Broderick,et al.  Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. , 1995 .

[4]  M. Kaste,et al.  Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS) , 1995, JAMA.

[5]  T. N. t-P. S. S. Group,et al.  Generalized efficacy of t-PA for acute stroke. Subgroup analysis of the NINDS t-PA Stroke Trial. , 1997, Stroke.

[6]  T. N. t-P. S. S. Group,et al.  Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. The NINDS t-PA Stroke Study Group. , 1997, Stroke.

[7]  P Trouillas,et al.  Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. , 1998, Lancet.

[8]  M. Kaste,et al.  Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II) , 1998, The Lancet.

[9]  G. Albers,et al.  Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. , 1999, JAMA.

[10]  S Hamilton,et al.  The rtPA (alteplase) 0- to 6-hour acute stroke trial, part A (A0276g) : results of a double-blind, placebo-controlled, multicenter study. Thromblytic therapy in acute ischemic stroke study investigators. , 2000, Stroke.

[11]  Domenico Inzitari,et al.  Stroke in an Elderly Population: Incidence and Impact on Survival and Daily Function , 2003, Cerebrovascular Diseases.

[12]  S. Sacco,et al.  Burden of first-ever ischemic stroke in the oldest old , 2004, Neurology.

[13]  A. Ziegler,et al.  Age and National Institutes of Health Stroke Scale Score Within 6 Hours After Onset Are Accurate Predictors of Outcome After Cerebral Ischemia: Development and External Validation of Prognostic Models , 2003, Stroke.

[14]  D. Clemmons.  Role of Insulin-Like Growth Factor Iin Maintaining Normal Glucose Homeostasis , 2005, Hormone Research in Paediatrics.

[15]  P. Heuschmann,et al.  Predictors of in-hospital mortality in patients with acute ischemic stroke treated with thrombolytic therapy. , 2004, JAMA.

[16]  Scott Hamilton,et al.  Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials , 2004, The Lancet.

[17]  Thrombolysis for Stroke in the Elderly , 2005, Journal of Thrombosis and Thrombolysis.

[18]  M. Reichhart,et al.  Thrombolysis in stroke patients aged 80 years and older: Swiss survey of IV thrombolysis , 2005, Neurology.

[19]  R. Sacco,et al.  Factors associated with in-hospital mortality after administration of thrombolysis in acute ischemic stroke patients: an analysis of the nationwide inpatient sample 1999 to 2002. , 2006, Stroke.

[20]  J. Grotta,et al.  Additional Outcomes and Subgroup Analyses of NXY-059 for Acute Ischemic Stroke in the SAINT I Trial , 2006, Stroke.

[21]  S. Engelter,et al.  Intravenous thrombolysis in stroke patients of > or = 80 versus < 80 years of age--a systematic review across cohort studies. , 2006, Age and ageing.

[22]  A. Buchan,et al.  Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian Alteplase for Stroke Effectiveness Study , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[23]  A. Buchan,et al.  Thrombolysis for acute ischemic stroke in patients older than 80 years , 2006 .

[24]  J. Saver,et al.  Confirmation of tPA Treatment Effect by Baseline Severity-Adjusted End Point Reanalysis of the NINDS-tPA Stroke Trials , 2007, Stroke.

[25]  W. Hacke,et al.  Thrombolytic therapy for acute ischaemic stroke in octogenarians: selection by magnetic resonance imaging improves safety but does not improve outcome , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[26]  J. Grotta,et al.  The Virtual International Stroke Trials Archive , 2007, Stroke.

[27]  V. Caso,et al.  Intravenous Thrombolysis with rt-PA in Acute Ischemic Stroke Patients Aged Older than 80 Years in Italy , 2007, Cerebrovascular Diseases.

[28]  Werner Hacke,et al.  Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study , 2007, The Lancet.

[29]  Peter Sandercock,et al.  The third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke , 2008, Trials.

[30]  M. Benatar,et al.  Outcome Analysis in Clinical Trial Design for Acute Stroke: Physicians’ Attitudes and Choices , 2008, Cerebrovascular Diseases.

[31]  J. Grotta,et al.  NXY-059 for the Treatment of Acute Stroke: Pooled Analysis of the SAINT I and II Trials , 2008, Stroke.

[32]  K. Dunnell.  Ageing and mortality in the UK--national statistician's annual article on the population. , 2008, Population trends.

[33]  M. Kaste,et al.  Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. , 2008, The New England journal of medicine.

[34]  M. Hill,et al.  Acute Ischaemic Stroke in Patients Aged 80 Years and Older , 2008, Drugs & aging.

[35]  Keith Muir,et al.  Thrombolysis with alteplase 3–4·5 h after acute ischaemic stroke (SITS-ISTR): an observational study , 2008, The Lancet.

[36]  J. Baron,et al.  Thrombolytic therapy for acute stroke in the United Kingdom: experience from the safe implementation of thrombolysis in stroke (SITS) register. , 2008, QJM : monthly journal of the Association of Physicians.

[37]  Justin A. Sattin,et al.  The Promise and Potential Pitfalls of Serum Biomarkers for Ischemic Stroke and Transient Ischemic Attack , 2008, The neurologist.

[38]  A. Rabinstein,et al.  Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study , 2008 .

[39]  D. Toni,et al.  Intravenous Thrombolysis with Rt-Pa in Acute Stroke Patients Aged ≥ 80 Years , 2009, International journal of stroke : official journal of the International Stroke Society.

[40]  Nimodipine BI Orgo,et al.  Should Stroke Trials Adjust Functional Outcome for Baseline Prognostic Factors ? , 2009 .

[41]  N. Wahlgren.  Systemic Thrombolysis in Clinical Practice: What Have We Learned after the Safe Implementation of Thrombolysis in Stroke Monitoring Study? , 2009, Cerebrovascular Diseases.

[42]  Norbert Nighoghossian,et al.  Thrombolysis, stroke-unit admission and early rehabilitation in elderly patients , 2009, Nature Reviews Neurology.

[43]  M. Walters,et al.  Functional Outcome Measures in Contemporary Stroke Trials , 2009, International journal of stroke : official journal of the International Stroke Society.

[44]  P. Bath,et al.  Should Stroke Trials Adjust Functional Outcome for Baseline Prognostic Factors? , 2009, Stroke.

[45]  W. Hacke,et al.  Mismatch-Based Delayed Thrombolysis: A Meta-Analysis , 2010, Stroke.

[46]  Gregory W Albers,et al.  Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials , 2010, The Lancet.