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. 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.
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.
RCT Entities:
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 strokepatients. Uncertainty persists as to whether low-dose alteplase confers benefits over standard-dose alteplase in acute ischemic strokepatients with RD. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616.
Authors: Patrick B Mark; Pardeep S Jhund; Matthew R Walters; Mark C Petrie; Albert Power; Claire White; Michele Robertson; Eugene Connolly; Stefan D Anker; Sunil Bhandari; Kenneth Farrington; Philip A Kalra; Charles R V Tomson; David C Wheeler; Christopher G Winearls; John J V McMurray; Iain C Macdougall; Ian Ford Journal: Kidney360 Date: 2021-09-16
Authors: Eivind Berge; William Whiteley; Heinrich Audebert; Gian Marco De Marchis; Ana Catarina Fonseca; Chiara Padiglioni; Natalia Pérez de la Ossa; Daniel Strbian; Georgios Tsivgoulis; Guillaume Turc Journal: Eur Stroke J Date: 2021-02-19