• 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, and ENCHANTED Investigators.
• 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.).
• Stroke. 2017 Sep 1; 48 (9): 2605-2609.

Background And PurposeRenal 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).MethodsA 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.ResultsCompared 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.ConclusionsRD 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 RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616.© 2017 American Heart Association, Inc.

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