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Effects of lowering LDL cholesterol on progression of kidney disease
Richard Haynes1, David Lewis1, Jonathan Emberson1
1Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom;
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.
Insights
Lowering LDL cholesterol with simvastatin and ezetimibe did not slow kidney disease progression in patients with chronic kidney disease (CKD). This study found no significant effect on end-stage renal disease (ESRD) or other renal outcomes.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Lowering LDL cholesterol is known to reduce atherosclerotic events.
- The impact of LDL cholesterol-lowering on chronic kidney disease (CKD) progression is uncertain.
- CKD patients are at increased risk for atherosclerotic events.
Purpose of the Study:
- To investigate the effect of simvastatin plus ezetimibe on the progression of kidney disease in patients with CKD.
- To determine if lowering LDL cholesterol impacts end-stage renal disease (ESRD) incidence.
- To assess the impact on other renal and mortality outcomes.
Main Methods:
- A randomized controlled trial involving 6245 participants with CKD not on dialysis.
- Participants were assigned to simvastatin (20 mg) plus ezetimibe (10 mg) daily or a matching placebo.
- Follow-up was 4.8 years, with ESRD as the primary renal outcome.
Main Results:
- Simvastatin plus ezetimibe achieved an average LDL cholesterol difference of 0.96 mmol/L compared to placebo.
- There was a nonsignificant 3% reduction in ESRD incidence (rate ratio, 0.97; 95% CI, 0.89 to 1.05; P=0.41).
- No significant effects were observed on ESRD or death, ESRD or doubling of creatinine, or the rate of eGFR change.
Conclusions:
- Lowering LDL cholesterol by approximately 1 mmol/L did not slow kidney disease progression within 5 years in a broad range of CKD patients.
- The combination of simvastatin and ezetimibe did not significantly impact ESRD or other key renal outcomes in this population.
- Further research may be needed to explore lipid-lowering strategies in CKD progression.
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