title: Effect of Estimated Glomerular Filtration Rate Decline on the Efficacy and Safety of Clopidogrel With Aspirin in Minor Stroke or Transient Ischemic Attack: CHANCE Substudy (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events).
abstract: Patients with chronic kidney disease (CKD) are at a particularly high risk for ischemic and bleeding events. Limited data exist as to the efficacy and safety of clopidogrel in stroke patients with renal dysfunction. Therefore, we sought to assess the impact of decreased kidney function on clinical outcomes for stroke patients on clopidogrel-aspirin treatment.
  
  
  
  Patients in the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) were randomized to clopidogrel-aspirin or aspirin-alone treatment. The primary efficacy outcome was new stroke during 90 days, whereas bleeding was the safety outcome. Patients were stratified according to estimated glomerular filtration rate.
  
  
  
  Dual clopidogrel-aspirin therapy was associated with a marked reduction in new strokes compared with the therapy of aspirin alone in patients with normal renal function (hazard ratio, 0.77; 95% confidence interval, 0.60-0.98; P=0.02) and mild CKD (hazard ratio, 0.60; 95% confidence interval, 0.45-0.79; P<0.01), whereas in patients with moderate CKD, no significant benefit from clopidogrel therapy was detected (hazard ratio, 1.00; 95% confidence interval, 0.43-2.35; P=0.99). There was no clear difference in bleeding episodes by treatment assignment across categories of renal impairment.
  
  
  
  Clopidogrel plus aspirin could decrease new stroke in patients with normal kidney function and mild CKD, but no extra benefit was observed in those with moderate CKD. Bleeding risk from the dual therapy did not seem to increase in mild or moderate CKD patients.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.
authors.affiliation: From the Department of Nephrology, Beijing Tiantan Hospital (Y.Z., Y.W.), Department of Neurology, Beijing Tiantan Hospital (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang), and Department of Epidemiology and Health Statistics, School of Public Health (Y.P.), Capital Medical University, China; China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria (D.W.); and Dell Medical School, University of Texas at Austin (S.C.J.).
authors.forename: Yilun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: From the Department of Nephrology, Beijing Tiantan Hospital (Y.Z., Y.W.), Department of Neurology, Beijing Tiantan Hospital (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang), and Department of Epidemiology and Health Statistics, School of Public Health (Y.P.), Capital Medical University, China; China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria (D.W.); and Dell Medical School, University of Texas at Austin (S.C.J.).
authors.forename: Yuesong
authors.initials: Y
authors.lastname: Pan
authors.affiliation: From the Department of Nephrology, Beijing Tiantan Hospital (Y.Z., Y.W.), Department of Neurology, Beijing Tiantan Hospital (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang), and Department of Epidemiology and Health Statistics, School of Public Health (Y.P.), Capital Medical University, China; China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria (D.W.); and Dell Medical School, University of Texas at Austin (S.C.J.).
authors.forename: Yu
authors.initials: Y
authors.lastname: Wu
authors.affiliation: From the Department of Nephrology, Beijing Tiantan Hospital (Y.Z., Y.W.), Department of Neurology, Beijing Tiantan Hospital (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang), and Department of Epidemiology and Health Statistics, School of Public Health (Y.P.), Capital Medical University, China; China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria (D.W.); and Dell Medical School, University of Texas at Austin (S.C.J.).
authors.forename: Xingquan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: From the Department of Nephrology, Beijing Tiantan Hospital (Y.Z., Y.W.), Department of Neurology, Beijing Tiantan Hospital (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang), and Department of Epidemiology and Health Statistics, School of Public Health (Y.P.), Capital Medical University, China; China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria (D.W.); and Dell Medical School, University of Texas at Austin (S.C.J.).
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: From the Department of Nephrology, Beijing Tiantan Hospital (Y.Z., Y.W.), Department of Neurology, Beijing Tiantan Hospital (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang), and Department of Epidemiology and Health Statistics, School of Public Health (Y.P.), Capital Medical University, China; China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria (D.W.); and Dell Medical School, University of Texas at Austin (S.C.J.).
authors.forename: David
authors.initials: D
authors.lastname: Wang
authors.affiliation: From the Department of Nephrology, Beijing Tiantan Hospital (Y.Z., Y.W.), Department of Neurology, Beijing Tiantan Hospital (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang), and Department of Epidemiology and Health Statistics, School of Public Health (Y.P.), Capital Medical University, China; China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria (D.W.); and Dell Medical School, University of Texas at Austin (S.C.J.).
authors.forename: S Claiborne
authors.initials: SC
authors.lastname: Johnston
authors.affiliation: From the Department of Nephrology, Beijing Tiantan Hospital (Y.Z., Y.W.), Department of Neurology, Beijing Tiantan Hospital (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang), and Department of Epidemiology and Health Statistics, School of Public Health (Y.P.), Capital Medical University, China; China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria (D.W.); and Dell Medical School, University of Texas at Austin (S.C.J.).
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.affiliation: From the Department of Nephrology, Beijing Tiantan Hospital (Y.Z., Y.W.), Department of Neurology, Beijing Tiantan Hospital (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang), and Department of Epidemiology and Health Statistics, School of Public Health (Y.P.), Capital Medical University, China; China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria (D.W.); and Dell Medical School, University of Texas at Austin (S.C.J.).
authors.forename: Chunxue
authors.initials: C
authors.lastname: Wang
authors.affiliation: From the Department of Nephrology, Beijing Tiantan Hospital (Y.Z., Y.W.), Department of Neurology, Beijing Tiantan Hospital (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang), and Department of Epidemiology and Health Statistics, School of Public Health (Y.P.), Capital Medical University, China; China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria (D.W.); and Dell Medical School, University of Texas at Austin (S.C.J.).
authors.forename: Xia
authors.initials: X
authors.lastname: Meng
authors.affiliation: From the Department of Nephrology, Beijing Tiantan Hospital (Y.Z., Y.W.), Department of Neurology, Beijing Tiantan Hospital (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang), and Department of Epidemiology and Health Statistics, School of Public Health (Y.P.), Capital Medical University, China; China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria (D.W.); and Dell Medical School, University of Texas at Austin (S.C.J.). yilong528@gmail.com yongjunwang1962@gmail.com.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From the Department of Nephrology, Beijing Tiantan Hospital (Y.Z., Y.W.), Department of Neurology, Beijing Tiantan Hospital (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang), and Department of Epidemiology and Health Statistics, School of Public Health (Y.P.), Capital Medical University, China; China National Clinical Research Center for Neurological Diseases, Beijing, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., X.Z., H.L., L.L., C.W., X.M., Yilong Wang, Yongjun Wang); INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria (D.W.); and Dell Medical School, University of Texas at Austin (S.C.J.). yilong528@gmail.com yongjunwang1962@gmail.com.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D000077144:Clopidogrel; D015897:Comorbidity; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000453:epidemiology; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy* / Q000453:epidemiology; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: chronic kidney disease; clopidogrel; stroke