In a 74‑year‑old woman with diabetes and chronic kidney disease stage 3a (eGFR ≈ 51 mL/min) who is taking rosuvastatin 5 mg and has LDL‑C 62 mg/dL, HDL‑C 34 mg/dL, and triglycerides 354 mg/dL, what is the optimal lipid‑lowering management?

Optimal Lipid Management in a 74-Year-Old Woman with Diabetes, CKD Stage 3a, and Severe Hypertriglyceridemia

Add fenofibrate 160 mg daily to address the severe hypertriglyceridemia (354 mg/dL) and low HDL-C (34 mg/dL), while continuing rosuvastatin 5 mg (which is already achieving the LDL-C goal of <70 mg/dL for high-risk diabetic patients with CKD). 1

Current Lipid Profile Assessment

Your patient's lipid panel reveals:

• LDL-C 62 mg/dL: Already at goal (<70 mg/dL for high-risk diabetic patients with CKD) 1
• HDL-C 34 mg/dL: Markedly low (goal >40 mg/dL for women)
• Triglycerides 354 mg/dL: Severely elevated (goal <150 mg/dL)
• Non-HDL-C 99 mg/dL (calculated: 133 - 34): At goal (<100 mg/dL for high-risk patients) 1

The dominant lipid abnormality is severe hypertriglyceridemia with low HDL-C, the classic diabetic dyslipidemia pattern that requires fibrate therapy. 1

Rationale for Adding Fenofibrate

Why Fenofibrate is the Priority

• Triglyceride reduction: Fenofibrate lowers triglycerides by 35-50% in diabetic patients with severe hypertriglyceridemia, which would bring your patient's level from 354 mg/dL to approximately 177-230 mg/dL. 2
• HDL-C elevation: Fenofibrate increases HDL-C by 10-20%, potentially raising her HDL from 34 mg/dL to 37-41 mg/dL. 2
• Pancreatitis prevention: At triglyceride levels >350 mg/dL, there is increased risk of acute pancreatitis; fibrates are specifically indicated to prevent this complication. 1, 3
• Cardiovascular benefit in diabetes: In diabetic patients with low HDL-C and elevated triglycerides (the exact profile of this patient), fibrate therapy provides additional cardiovascular risk reduction beyond statins. 1

Statin Dosing in CKD Stage 3a

Continue rosuvastatin 5 mg without dose adjustment. 1, 4, 5

• No dose reduction needed at eGFR 51 mL/min: KDIGO guidelines recommend dose reduction of statins only when eGFR falls below 45 mL/min/1.73 m², and even then, rosuvastatin 5-10 mg daily is safe and appropriate. 1, 4
• Rosuvastatin pharmacokinetics in CKD: The FDA label states that mild-to-moderate renal impairment (CrCl ≥30 mL/min) has no influence on rosuvastatin plasma concentrations; dose adjustment is only required for severe renal impairment (CrCl <30 mL/min). 5
• LDL-C already at goal: Her LDL-C of 62 mg/dL is below the target of <70 mg/dL for high-risk diabetic patients with CKD, so statin intensification is not indicated. 1
• Asian ethnicity consideration: If your patient is of Asian descent, rosuvastatin 5 mg is the appropriate starting dose due to 2-fold higher drug exposure in this population. 5

Specific Treatment Algorithm

Step 1: Initiate Fenofibrate

• Dose: Fenofibrate 160 mg once daily (or fenofibric acid 135 mg once daily if preferred formulation) 2
• Timing: Can be taken with or without food; if combined with rosuvastatin, separate administration by at least 2 hours to minimize interaction risk 1
• Monitoring: Check lipid panel, liver enzymes (ALT/AST), and creatinine at 8-12 weeks after initiation 1, 2

Step 2: Continue Rosuvastatin 5 mg Daily

• No dose adjustment needed at eGFR 51 mL/min 1, 4, 5
• Monitor for myopathy: The combination of rosuvastatin + fenofibrate carries a low but measurable risk of myopathy (approximately 1-2%); check baseline CK and monitor for muscle symptoms 1
• Avoid gemfibrozil: Never use gemfibrozil with statins due to significantly higher myopathy risk; fenofibrate is the preferred fibrate for combination therapy 1, 3

Step 3: Reassess at 8-12 Weeks

Target lipid goals:

• Triglycerides <150 mg/dL (ideally <135 mg/dL for high-risk diabetic patients) 3
• HDL-C >40 mg/dL for women 1
• LDL-C <70 mg/dL (already achieved) 1
• Non-HDL-C <100 mg/dL (already achieved) 1

If triglycerides remain >200 mg/dL despite fenofibrate:

• Optimize glycemic control (HbA1c <7% if safely achievable) 1
• Reinforce lifestyle modifications: weight loss, reduced carbohydrate intake, alcohol restriction, increased physical activity 1, 3
• Consider adding icosapent ethyl 2 grams twice daily if triglycerides remain 135-499 mg/dL despite optimized therapy 3

Critical Safety Considerations

Myopathy Risk with Statin-Fibrate Combination

• Baseline CK measurement: Obtain CK before starting fenofibrate 1
• Patient education: Instruct patient to report any unexplained muscle pain, tenderness, or weakness immediately 1
• CK monitoring: If symptoms develop, check CK; if CK >10× ULN, discontinue both agents and monitor renal function 1
• Lower risk with fenofibrate: Fenofibrate has significantly lower myopathy risk than gemfibrozil when combined with statins 1, 3

Renal Function Monitoring

• Fenofibrate and creatinine: Fenofibrate can cause a reversible 10-15% increase in serum creatinine due to altered tubular secretion (not true nephrotoxicity); this is expected and does not require dose adjustment unless creatinine rises >30% from baseline 2
• Rosuvastatin renal safety: Multiple studies demonstrate that rosuvastatin does not worsen renal function in CKD patients; some evidence suggests potential renal protective effects 6, 7
• Monitor eGFR: Recheck eGFR at 8-12 weeks; if eGFR declines to <30 mL/min, reduce rosuvastatin to 5 mg daily (already at this dose) and consider fenofibrate dose reduction 1, 4, 5

Hepatotoxicity Monitoring

• Baseline liver enzymes: Check ALT/AST before starting fenofibrate 2
• Follow-up testing: Recheck at 8-12 weeks; if ALT >3× ULN, discontinue fenofibrate 1
• Alcohol consumption: Counsel patient to limit alcohol intake, as chronic alcohol use increases risk of hepatotoxicity with both statins and fibrates 5

Alternative Considerations if Fenofibrate is Not Tolerated

If Fenofibrate Causes Myopathy or GI Intolerance

1. Icosapent ethyl 2 grams twice daily: Lowers triglycerides by 20-30% and has cardiovascular outcome benefit in high-risk diabetic patients with triglycerides 135-499 mg/dL 3
2. Omega-3 fatty acids 4 grams daily: Modest triglyceride reduction (15-20%) with excellent safety profile 3
3. Niacin (use with caution): Can raise HDL-C by 15-25% and lower triglycerides by 20-30%, but may worsen glycemic control in diabetics; limit to ≤2 grams/day and monitor HbA1c closely 1, 3

If Triglycerides Exceed 500 mg/dL

• Urgent fibrate initiation to prevent acute pancreatitis 1, 3
• Consider referral to lipid specialist for complex mixed dyslipidemia management 3

Why Not Intensify the Statin?

• LDL-C already at goal: At 62 mg/dL, her LDL-C is below the target of <70 mg/dL for high-risk diabetic patients with CKD 1
• Statins have limited effect on triglycerides: High-dose statins lower triglycerides by only 10-20%, which would be insufficient to address her severe hypertriglyceridemia 1
• Increased myopathy risk: Higher statin doses in CKD patients increase the risk of muscle-related adverse events without addressing the primary lipid abnormality (hypertriglyceridemia) 1, 4

Why Not Add Ezetimibe or Bempedoic Acid?

• LDL-C already at goal: Ezetimibe and bempedoic acid primarily lower LDL-C, which is already adequately controlled at 62 mg/dL 3
• Minimal effect on triglycerides: Neither agent significantly lowers triglycerides or raises HDL-C 3
• Wrong target: The dominant lipid abnormality is hypertriglyceridemia with low HDL-C, not elevated LDL-C 1

Common Pitfalls to Avoid

1. Do not use gemfibrozil with rosuvastatin: Gemfibrozil significantly increases statin levels and myopathy risk; fenofibrate is the only fibrate that should be combined with statins 1, 3
2. Do not discontinue rosuvastatin: Even though LDL-C is at goal, continuing statin therapy provides ongoing cardiovascular protection in this high-risk diabetic patient with CKD 1
3. Do not ignore the low HDL-C: Low HDL-C (<40 mg/dL) is an independent cardiovascular risk factor in diabetic patients and requires treatment with fibrates or niacin 1
4. Do not delay fibrate therapy: At triglyceride levels >350 mg/dL, there is increased risk of acute pancreatitis; fibrate therapy should be initiated promptly 1, 3
5. Do not misinterpret creatinine rise with fenofibrate: A modest (10-15%) increase in serum creatinine is expected with fenofibrate due to altered tubular secretion and does not represent true nephrotoxicity 2