Effects of Lowering LDL Cholesterol on Progression of Kidney Disease

Richard Haynes, David Lewis, Joanthan Emberson, Christina Reith, Lawrence Agodoa, Alan Cass, Jonathan Craig, Dick de Zeeuw, Bo Feldt-Rasmussen, Beng Fellström, Adeera Levin, David Wheeler, Rob Walker, William Herrington, Colin Baigent, Martin Landray

Research output: Contribution to journalArticleResearchpeer-review

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 1mmol/L did not slowkidney disease progressionwithin 5 years in awide range of patients withCKD.
Original languageEnglish
Pages (from-to)1825-1833
Number of pages9
JournalJournal of the American Society of Nephrology : JASN
Volume25
Issue number8
DOIs
Publication statusPublished - Aug 2014

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Kidney Diseases
Simvastatin
LDL Cholesterol
Placebos
Chronic Kidney Failure
Dialysis
Confidence Intervals
Kidney Transplantation
Creatinine
Therapeutics
Maintenance
Kidney
Ezetimibe
Incidence

Cite this

Haynes, Richard ; Lewis, David ; Emberson, Joanthan ; Reith, Christina ; Agodoa, Lawrence ; Cass, Alan ; Craig, Jonathan ; de Zeeuw, Dick ; Feldt-Rasmussen, Bo ; Fellström, Beng ; Levin, Adeera ; Wheeler, David ; Walker, Rob ; Herrington, William ; Baigent, Colin ; Landray, Martin. / Effects of Lowering LDL Cholesterol on Progression of Kidney Disease. In: Journal of the American Society of Nephrology : JASN. 2014 ; Vol. 25, No. 8. pp. 1825-1833.
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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 1mmol/L did not slowkidney disease progressionwithin 5 years in awide range of patients withCKD.",
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Haynes, R, Lewis, D, Emberson, J, Reith, C, Agodoa, L, Cass, A, Craig, J, de Zeeuw, D, Feldt-Rasmussen, B, Fellström, B, Levin, A, Wheeler, D, Walker, R, Herrington, W, Baigent, C & Landray, M 2014, 'Effects of Lowering LDL Cholesterol on Progression of Kidney Disease', Journal of the American Society of Nephrology : JASN, vol. 25, no. 8, pp. 1825-1833. https://doi.org/10.1681/ASN.2013090965

Effects of Lowering LDL Cholesterol on Progression of Kidney Disease. / Haynes, Richard; Lewis, David; Emberson, Joanthan; Reith, Christina; Agodoa, Lawrence; Cass, Alan; Craig, Jonathan; de Zeeuw, Dick; Feldt-Rasmussen, Bo; Fellström, Beng; Levin, Adeera; Wheeler, David; Walker, Rob; Herrington, William; Baigent, Colin; Landray, Martin.

In: Journal of the American Society of Nephrology : JASN, Vol. 25, No. 8, 08.2014, p. 1825-1833.

Research output: Contribution to journalArticleResearchpeer-review

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

AU - Haynes, Richard

AU - Lewis, David

AU - Emberson, Joanthan

AU - Reith, Christina

AU - Agodoa, Lawrence

AU - Cass, Alan

AU - Craig, Jonathan

AU - de Zeeuw, Dick

AU - Feldt-Rasmussen, Bo

AU - Fellström, Beng

AU - Levin, Adeera

AU - Wheeler, David

AU - Walker, Rob

AU - Herrington, William

AU - Baigent, Colin

AU - Landray, Martin

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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 1mmol/L did not slowkidney disease progressionwithin 5 years in awide range of patients withCKD.

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 1mmol/L did not slowkidney disease progressionwithin 5 years in awide range of patients withCKD.

KW - creatinine

KW - ezetimibe

KW - low density lipoprotein cholesterol

KW - placebo

KW - simvastatin

KW - acute kidney failure

KW - adult

KW - Article

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KW - comparative study

KW - controlled study

KW - creatinine blood level

KW - diabetic nephropathy

KW - dialysis

KW - disease course

KW - end stage renal disease

KW - female

KW - follow up

KW - human

KW - kidney disease

KW - kidney polycystic disease

KW - kidney transplantation

KW - major clinical study

KW - male

KW - priority journal

KW - proteinuria

KW - randomized controlled trial

KW - renovascular disease

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DO - 10.1681/ASN.2013090965

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JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

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