Effects of lowering LDL cholesterol on progression of kidney disease.
Lowering LDL cholesterol reduces the risk of developing atherosclerotic events in CKD, but the effects of such treatment on progression of kidney disease remain uncertain. Here, 6245 participants with CKD (not on dialysis) were randomly assigned to simvastatin (20 mg) plus ezetimibe (10 mg) daily or matching placebo. The main prespecified renal outcome was ESRD (defined as the initiation of maintenance dialysis or kidney transplantation). During 4.8 years of follow-up, allocation to simvastatin plus ezetimibe resulted in an average LDL cholesterol difference (SEM) of 0.96 (0.02) mmol/L compared with placebo. There was a nonsignificant 3% reduction in the incidence of ESRD (1057 [33.9%] cases with simvastatin plus ezetimibe versus 1084 [34.6%] cases with placebo; rate ratio, 0.97; 95% confidence interval [95% CI], 0.89 to 1.05; P=0.41). Similarly, allocation to simvastatin plus ezetimibe had no significant effect on the prespecified tertiary outcomes of ESRD or death (1477 [47.4%] events with treatment versus 1513 [48.3%] events with placebo; rate ratio, 0.97; 95% CI, 0.90 to 1.04; P=0.34) or ESRD or doubling of baseline creatinine (1189 [38.2%] events with treatment versus 1257 [40.2%] events with placebo; rate ratio, 0.93; 95% CI, 0.86 to 1.01; P=0.09). Exploratory analyses also showed no significant effect on the rate of change in eGFR. Lowering LDL cholesterol by 1 mmol/L did not slow kidney disease progression within 5 years in a wide range of patients with CKD.
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom;
Richard
R
Haynes
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom;
David
D
Lewis
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom;
Jonathan
J
Emberson
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom;
Christina
C
Reith
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
Lawrence
L
Agodoa
Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia;
Alan
A
Cass
Sydney School of Public Health, Children's Hospital at Westmead, University of Sydney, Sydney, New South Wales, Australia;
Jonathan C
JC
Craig
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands;
Dick
D
de Zeeuw
Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;
Bo
B
Feldt-Rasmussen
University Hospital, Uppsala, Sweden;
Bengt
B
Fellström
University of British Columbia, Vancouver, British Columbia, Canada;
Adeera
A
Levin
University College London, London, United Kingdom; and.
David C
DC
Wheeler
Dunedin School of Medicine, University of Otago, Otago, New Zealand.
Rob
R
Walker
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom;
William G
WG
Herrington
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom;
Colin
C
Baigent
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; sharpclinical@ctsu.ox.ac.uk.
Martin J
MJ
Landray
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000473:pathology* / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019821:Simvastatin; D000069438:Ezetimibe