Is ezetimibe (cholesterol absorption inhibitor) contraindicated in patients with Chronic Kidney Disease (CKD)?

Ezetimibe is NOT Contraindicated in CKD

Ezetimibe is explicitly recommended for use in patients with CKD stages 3a-5 (eGFR <60 mL/min/1.73 m²), either as monotherapy or in combination with a statin, and is considered safe and effective in this population. 1

Guideline-Based Recommendations for Ezetimibe in CKD

CKD Stages 3a-5 (Non-Dialysis)

• For adults ≥50 years with eGFR <60 mL/min/1.73 m² not on dialysis, KDIGO strongly recommends (Grade 1A) treatment with either a statin alone OR a statin/ezetimibe combination. 1
• This recommendation is based on the landmark SHARP trial, which demonstrated that simvastatin/ezetimibe combination therapy significantly reduced major atherosclerotic events (coronary death, MI, non-hemorrhagic stroke, or revascularization) compared to placebo in patients with CKD stages 3a-5. 1
• The European Society of Cardiology (ESC/EAS 2016) similarly indicates that statin/ezetimibe combination is appropriate for non-dialysis-dependent CKD patients. 1

CKD Stages 1-2 (eGFR ≥60 mL/min/1.73 m²)

• For adults ≥50 years with CKD stages 1-2, statin monotherapy is recommended (Grade 1B), with ezetimibe reserved as add-on therapy if needed. 1

Dialysis-Dependent CKD

• In dialysis patients, statins or statin/ezetimibe should NOT be initiated (Grade 2A). 1
• However, if patients are already receiving these agents at dialysis initiation, continuation is suggested (Grade 2C). 1
• This reflects the substantially smaller relative risk reduction observed in dialysis patients compared to earlier CKD stages. 1

Safety Profile in CKD

Evidence of Safety

• Ezetimibe can be safely administered to patients with CKD, with no dose adjustment required regardless of renal function severity. 2, 3
• A 24-week study in CKD patients with dyslipidemia showed no adverse events with ezetimibe 10 mg daily, while demonstrating significant reductions in LDL-C, remnant-like lipoprotein cholesterol, and lipoprotein(a). 2
• The UK-HARP-II study confirmed that adding ezetimibe to simvastatin was both safe and effective in treating dyslipidemia in CKD patients. 3

Renal Protective Effects

• Beyond lipid lowering, ezetimibe may provide renal protection in CKD patients. 2
• Studies have shown significant decreases in urine protein-to-creatinine ratio and brachial-ankle pulse wave velocity without changes in eGFR, suggesting potential anti-proteinuric and vascular protective effects. 2

Clinical Implementation Algorithm

Step 1: Determine CKD Stage and Age

• If age ≥50 years AND eGFR <60 mL/min/1.73 m² (stages 3a-5) AND not on dialysis → Initiate statin or statin/ezetimibe combination 1
• If age ≥50 years AND eGFR ≥60 mL/min/1.73 m² (stages 1-2) → Initiate statin monotherapy 1
• If age 18-49 years with additional risk factors (known CAD, diabetes, prior stroke, or 10-year CV risk ≥10%) → Consider statin therapy 1

Step 2: Consider Ezetimibe Addition

• For CKD stages 3a-5, ezetimibe can be used upfront with a statin or added if LDL-C remains elevated on statin monotherapy. 1, 4
• Typical dose: ezetimibe 10 mg daily (no renal dose adjustment needed). 4, 2

Step 3: Monitoring

• Do NOT use LDL-C levels to guide initiation decisions in CKD stages 3-5, as LDL-C is not a reliable predictor of CV risk in this population. 1, 4
• Reassess renal function (eGFR, creatinine) every 3-6 months to monitor CKD progression. 4
• Monitor for statin-related adverse effects at each visit. 4

Important Caveats

Dialysis Exception

• The only CKD population where ezetimibe initiation is NOT recommended is dialysis-dependent patients without pre-existing atherosclerotic CVD, due to limited evidence of benefit in this specific group. 1

Evidence Limitations

• While ezetimibe effectively reduces cholesterol in CKD, independent cardiovascular outcome data for ezetimibe alone (without statins) in CKD remains limited. 5, 6
• The SHARP trial used combination therapy, making it difficult to isolate ezetimibe's independent contribution. 5

Kidney Transplant Recipients

• Ezetimibe combined with statins is effective and safe in kidney transplant recipients with dyslipidemia. 3