Effects of Lowering LDL Cholesterol on Progression of Kidney Disease

Richard Haynes; David Lewis; Jonathan Emberson; Christina Reith; Lawrence Agodoa; Alan Cass; Jonathan C Craig; Dick de Zeeuw; Bo Feldt-Rasmussen; Bengt Fellström; Adeera Levin; David C Wheeler; Rob Walker; William G Herrington; Colin Baigent; Martin J Landray; SHARP Collaborative Group

doi:10.1681/ASN.2013090965

Effects of Lowering LDL Cholesterol on Progression of Kidney Disease

Richard Haynes, David Lewis, Jonathan Emberson, Christina Reith, Lawrence Agodoa, Alan Cass, Jonathan C Craig, Dick de Zeeuw, Bo Feldt-Rasmussen, Bengt Fellström, Adeera Levin, David C Wheeler, Rob Walker, William G Herrington, Colin Baigent, Martin J Landray, SHARP Collaborative Group

Institut for Klinisk Medicin

96 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Journal of the American Society of Nephrology
Vol/bind	25
Udgave nummer	8
Sider (fra-til)	1825-1833
Antal sider	9
ISSN	1046-6673
DOI	https://doi.org/10.1681/ASN.2013090965
Status	Udgivet - 1 aug. 2014

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10.1681/ASN.2013090965

Citationsformater

Haynes, R., Lewis, D., Emberson, J., Reith, C., Agodoa, L., Cass, A., Craig, J. C., de Zeeuw, D., Feldt-Rasmussen, B., Fellström, B., Levin, A., Wheeler, D. C., Walker, R., Herrington, W. G., Baigent, C., Landray, M. J., & SHARP Collaborative Group (2014). Effects of Lowering LDL Cholesterol on Progression of Kidney Disease. Journal of the American Society of Nephrology, 25(8), 1825-1833. https://doi.org/10.1681/ASN.2013090965

Haynes, R, Lewis, D, Emberson, J, Reith, C, Agodoa, L, Cass, A, Craig, JC, de Zeeuw, D, Feldt-Rasmussen, B, Fellström, B, Levin, A, Wheeler, DC, Walker, R, Herrington, WG, Baigent, C, Landray, MJ & SHARP Collaborative Group 2014, 'Effects of Lowering LDL Cholesterol on Progression of Kidney Disease', Journal of the American Society of Nephrology, bind 25, nr. 8, s. 1825-1833. https://doi.org/10.1681/ASN.2013090965

@article{4350b12da18e4b84b4f9c89d70da600c,

title = "Effects of Lowering LDL Cholesterol on Progression of Kidney Disease",

abstract = "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.",

keywords = "Aged, Anticholesteremic Agents, Azetidines, Cholesterol, LDL, Disease Progression, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Incidence, Kidney Failure, Chronic, Kidney Transplantation, Male, Middle Aged, Renal Dialysis, Simvastatin, Treatment Outcome",

author = "Richard Haynes and David Lewis and Jonathan Emberson and Christina Reith and Lawrence Agodoa and Alan Cass and Craig, {Jonathan C} and {de Zeeuw}, Dick and Bo Feldt-Rasmussen and Bengt Fellstr{\"o}m and Adeera Levin and Wheeler, {David C} and Rob Walker and Herrington, {William G} and Colin Baigent and Landray, {Martin J} and {SHARP Collaborative Group}",

note = "Copyright {\textcopyright} 2014 by the American Society of Nephrology.",

year = "2014",

month = aug,

day = "1",

doi = "10.1681/ASN.2013090965",

language = "English",

volume = "25",

pages = "1825--1833",

journal = "Journal of the American Society of Nephrology",

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TY - JOUR

T1 - Effects of Lowering LDL Cholesterol on Progression of Kidney Disease

AU - Haynes, Richard

AU - Lewis, David

AU - Emberson, Jonathan

AU - Reith, Christina

AU - Agodoa, Lawrence

AU - Cass, Alan

AU - Craig, Jonathan C

AU - de Zeeuw, Dick

AU - Feldt-Rasmussen, Bo

AU - Fellström, Bengt

AU - Levin, Adeera

AU - Wheeler, David C

AU - Walker, Rob

AU - Herrington, William G

AU - Baigent, Colin

AU - Landray, Martin J

AU - SHARP Collaborative Group

PY - 2014/8/1

Y1 - 2014/8/1

N2 - 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.

AB - 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.

KW - Aged

KW - Anticholesteremic Agents

KW - Azetidines

KW - Cholesterol, LDL

KW - Disease Progression

KW - Drug Therapy, Combination

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Incidence

KW - Kidney Failure, Chronic

KW - Kidney Transplantation

KW - Male

KW - Middle Aged

KW - Renal Dialysis

KW - Simvastatin

KW - Treatment Outcome

U2 - 10.1681/ASN.2013090965

DO - 10.1681/ASN.2013090965

M3 - Journal article

C2 - 24790178

SN - 1046-6673

VL - 25

SP - 1825

EP - 1833

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

IS - 8

ER -

Effects of Lowering LDL Cholesterol on Progression of Kidney Disease

Abstract

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