Influence of Renal Impairment on Outcome for Thrombolysis-Treated Acute Ischemic Stroke ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) Post Hoc Analysis
Journal
Stroke
ISSN
0039-2499
1524-4628
Date Issued
2017
Author(s)
Susan J. Carr
Xia Wang
VERONICA VIVIANA OLAVARRIA IANISZEWSKY
Pablo M. Lavados
Jorge A. Rodriguez
Jong S. Kim
Tsong-Hai Lee
Richard I. Lindley
Octavio M. Pontes-Neto
Stefano Ricci
Shoichiro Sato
Vijay K. Sharma
Mark Woodward
John Chalmers
Craig S. Anderson
Thompson G. Robinson
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:sec>
<jats:title>Background and Purpose—</jats:title>
<jats:p>Renal dysfunction (RD) is associated with poor prognosis after stroke. We assessed the effects of RD on outcomes and interaction with low- versus standard-dose alteplase in a post hoc subgroup analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study).</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods—</jats:title>
<jats:p>
A total of 3220 thrombolysis-eligible patients with acute ischemic stroke (mean age, 66.5 years; 37.8% women) were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset. Six hundred and fifty-nine (19.8%) patients had moderate-to-severe RD (estimated glomerular filtration rate, <60 mL/min per 1.73 m
<jats:sup>2</jats:sup>
) at baseline. The impact of RD on death or disability (modified Rankin Scale scores, 2–6) at 90 days, and symptomatic intracerebral hemorrhage, was assessed in logistic regression models.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results—</jats:title>
<jats:p>
Compared with patients with normal renal function (>90 mL/min per 1.73 m
<jats:sup>2</jats:sup>
), those with severe RD (<30 mL/min per 1.73 m
<jats:sup>2</jats:sup>
) had increased mortality (adjusted odds ratio, 2.07; 95% confidence interval, 0.89–4.82;
<jats:italic>P</jats:italic>
=0.04 for trend); every 10 mL/min per 1.73 m
<jats:sup>2</jats:sup>
lower estimated glomerular filtration rate was associated with an adjusted 9% increased odds of death from thrombolysis-treated acute ischemic stroke. There was no significant association with modified Rankin Scale scores 2 to 6 (adjusted odds ratio, 1.03; 95% confidence interval, 0.62–1.70;
<jats:italic>P</jats:italic>
=0.81 for trend), modified Rankin Scale 3 to 6 (adjusted odds ratio, 1.20; 95% confidence interval, 0.72–2.01;
<jats:italic>P</jats:italic>
=0.44 for trend), or symptomatic intracerebral hemorrhage, or any heterogeneity in comparative treatment effects between low-dose and standard-dose alteplase by RD grades.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions—</jats:title>
<jats:p>RD is associated with increased mortality but not disability or symptomatic intracerebral hemorrhage in thrombolysis-eligible and treated acute ischemic stroke patients. Uncertainty persists as to whether low-dose alteplase confers benefits over standard-dose alteplase in acute ischemic stroke patients with RD.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Clinical Trial Registration—</jats:title>
<jats:p>
URL:
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link>
. Unique identifier: NCT01422616.
</jats:p>
</jats:sec>
<jats:title>Background and Purpose—</jats:title>
<jats:p>Renal dysfunction (RD) is associated with poor prognosis after stroke. We assessed the effects of RD on outcomes and interaction with low- versus standard-dose alteplase in a post hoc subgroup analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study).</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods—</jats:title>
<jats:p>
A total of 3220 thrombolysis-eligible patients with acute ischemic stroke (mean age, 66.5 years; 37.8% women) were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset. Six hundred and fifty-nine (19.8%) patients had moderate-to-severe RD (estimated glomerular filtration rate, <60 mL/min per 1.73 m
<jats:sup>2</jats:sup>
) at baseline. The impact of RD on death or disability (modified Rankin Scale scores, 2–6) at 90 days, and symptomatic intracerebral hemorrhage, was assessed in logistic regression models.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results—</jats:title>
<jats:p>
Compared with patients with normal renal function (>90 mL/min per 1.73 m
<jats:sup>2</jats:sup>
), those with severe RD (<30 mL/min per 1.73 m
<jats:sup>2</jats:sup>
) had increased mortality (adjusted odds ratio, 2.07; 95% confidence interval, 0.89–4.82;
<jats:italic>P</jats:italic>
=0.04 for trend); every 10 mL/min per 1.73 m
<jats:sup>2</jats:sup>
lower estimated glomerular filtration rate was associated with an adjusted 9% increased odds of death from thrombolysis-treated acute ischemic stroke. There was no significant association with modified Rankin Scale scores 2 to 6 (adjusted odds ratio, 1.03; 95% confidence interval, 0.62–1.70;
<jats:italic>P</jats:italic>
=0.81 for trend), modified Rankin Scale 3 to 6 (adjusted odds ratio, 1.20; 95% confidence interval, 0.72–2.01;
<jats:italic>P</jats:italic>
=0.44 for trend), or symptomatic intracerebral hemorrhage, or any heterogeneity in comparative treatment effects between low-dose and standard-dose alteplase by RD grades.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions—</jats:title>
<jats:p>RD is associated with increased mortality but not disability or symptomatic intracerebral hemorrhage in thrombolysis-eligible and treated acute ischemic stroke patients. Uncertainty persists as to whether low-dose alteplase confers benefits over standard-dose alteplase in acute ischemic stroke patients with RD.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Clinical Trial Registration—</jats:title>
<jats:p>
URL:
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link>
. Unique identifier: NCT01422616.
</jats:p>
</jats:sec>
Subjects
glomerular filtration rate
;
hypertension
;
intracranial hemorrhages
;
odds ratio
;
stroke