Influence of Renal Impairment on Outcome for Thrombolysis-Treated Acute Ischemic Stroke: ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) Post Hoc Analysis

Susan J Carr; Xia Wang; Veronica V Olavarria; 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; ENCHANTED Investigators

doi:10.1161/STROKEAHA.117.017808

Influence of Renal Impairment on Outcome for Thrombolysis-Treated Acute Ischemic Stroke: ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) Post Hoc Analysis

Stroke. 2017 Sep;48(9):2605-2609. doi: 10.1161/STROKEAHA.117.017808. Epub 2017 Jul 24.

Authors

Susan J Carr¹, Xia Wang¹, Veronica V Olavarria¹, Pablo M Lavados¹, Jorge A Rodriguez¹, Jong S Kim¹, Tsong-Hai Lee¹, Richard I Lindley¹, Octavio M Pontes-Neto¹, Stefano Ricci¹, Shoichiro Sato¹, Vijay K Sharma¹, Mark Woodward¹, John Chalmers¹, Craig S Anderson¹, Thompson G Robinson²; ENCHANTED Investigators

Affiliations

¹ From the John Walls Renal Unit, University Hospitals of Leicester NHS Trust, United Kingdom (S.J.C.); The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia (X.W., M.W., J.C., C.S.A.); The George Institute for Global Health, University of Sydney, New South Wales, Australia (R.I.L.); Clinica Alemana de Santiago, Facultad de Medicina, Clinica Alemana, Universidad del Desarrollo, Santiago, Chile (V.V.O., P.M.L., J.A.R.); Departamento de Ciencias Neurológicas, Facultad de Medicina, Universidad de Chile, Santiago (P.M.L.); Facultad de Medicina, Universidad Andrés Bello, Santiago, Chile (J.A.R.); Department of Neurology, Asan Medical Center, University of Ulsan, Seoul, Korea (J.S.K.); Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan (T.-H.L.); Westmead Clinical School (R.I.L.) and School of Public Health (M.W.), University of Sydney, New South Wales, Australia; Department of Neurosciences and Behavioral Sciences, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil (O.M.P.-N.); Uo Neurologia, USL Umbria 1, Sedi di Citta di Castello e Branca, Italy (S.R.); Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (S.S.); Yong Loo Lin School of Medicine, National University of Singapore and National University Hospital (V.K.S.); Department of Epidemiology, Johns Hopkins University, Baltimore, MD (M.W.); The George Institute for Global Health, University of Oxford, United Kingdom (M.W.); Neurology Department, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (C.S.A.); The George Institute China at Peking University Health Sciences Center, Beijing (C.S.A.); and Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, United Kingdom (T.G.R.).
² From the John Walls Renal Unit, University Hospitals of Leicester NHS Trust, United Kingdom (S.J.C.); The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia (X.W., M.W., J.C., C.S.A.); The George Institute for Global Health, University of Sydney, New South Wales, Australia (R.I.L.); Clinica Alemana de Santiago, Facultad de Medicina, Clinica Alemana, Universidad del Desarrollo, Santiago, Chile (V.V.O., P.M.L., J.A.R.); Departamento de Ciencias Neurológicas, Facultad de Medicina, Universidad de Chile, Santiago (P.M.L.); Facultad de Medicina, Universidad Andrés Bello, Santiago, Chile (J.A.R.); Department of Neurology, Asan Medical Center, University of Ulsan, Seoul, Korea (J.S.K.); Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan (T.-H.L.); Westmead Clinical School (R.I.L.) and School of Public Health (M.W.), University of Sydney, New South Wales, Australia; Department of Neurosciences and Behavioral Sciences, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil (O.M.P.-N.); Uo Neurologia, USL Umbria 1, Sedi di Citta di Castello e Branca, Italy (S.R.); Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (S.S.); Yong Loo Lin School of Medicine, National University of Singapore and National University Hospital (V.K.S.); Department of Epidemiology, Johns Hopkins University, Baltimore, MD (M.W.); The George Institute for Global Health, University of Oxford, United Kingdom (M.W.); Neurology Department, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (C.S.A.); The George Institute China at Peking University Health Sciences Center, Beijing (C.S.A.); and Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, United Kingdom (T.G.R.). tgr2@le.ac.uk.

PMID: 28739832
DOI: 10.1161/STROKEAHA.117.017808

Abstract

Background and purpose: 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).

Methods: 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 m²) 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.

Results: Compared with patients with normal renal function (>90 mL/min per 1.73 m²), those with severe RD (<30 mL/min per 1.73 m²) had increased mortality (adjusted odds ratio, 2.07; 95% confidence interval, 0.89-4.82; P=0.04 for trend); every 10 mL/min per 1.73 m² 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; P=0.81 for trend), modified Rankin Scale 3 to 6 (adjusted odds ratio, 1.20; 95% confidence interval, 0.72-2.01; P=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.

Conclusions: 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.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616.

Keywords: glomerular filtration rate; hypertension; intracranial hemorrhages; odds ratio; stroke.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Intravenous
Aged
Aged, 80 and over
Brain Ischemia / drug therapy*
Brain Ischemia / epidemiology
Brain Ischemia / mortality
Cerebral Hemorrhage / chemically induced
Comorbidity
Female
Fibrinolytic Agents / therapeutic use*
Glomerular Filtration Rate
Humans
Logistic Models
Male
Middle Aged
Odds Ratio
Prognosis
Randomized Controlled Trials as Topic
Renal Insufficiency, Chronic / epidemiology*
Stroke / drug therapy*
Stroke / epidemiology
Stroke / mortality
Thrombolytic Therapy
Tissue Plasminogen Activator / therapeutic use*
Treatment Outcome

Substances

Fibrinolytic Agents
Tissue Plasminogen Activator

Associated data

ClinicalTrials.gov/NCT01422616