Fenofibrate for Hypertriglyceridemia
Fenofibrate is the first-line pharmacological treatment for severe hypertriglyceridemia (≥500 mg/dL) to reduce the risk of pancreatitis, while for moderate hypertriglyceridemia (150-499 mg/dL), statins remain the first-line therapy with fenofibrate as an adjunctive option. 1, 2, 3
Classification and Treatment Approach
Moderate Hypertriglyceridemia (150-499 mg/dL)
- First-line therapy: Statins (targeting LDL-C as primary goal)
- Secondary target: Non-HDL-C (goal is 30 mg/dL higher than LDL-C goal) 1
- Adjunctive therapy: Consider adding fenofibrate if triglycerides remain elevated despite statin therapy 1, 2
Severe Hypertriglyceridemia (500-999 mg/dL)
- First-line therapy: Fenofibrate (to reduce pancreatitis risk) 1, 2, 3
- Initial dose: 54-160 mg daily, individualized according to patient response 3
- Maximum dose: 160 mg once daily 3
Very Severe Hypertriglyceridemia (≥1000 mg/dL)
- Immediate intervention: Very low-fat diet (<10-15% of calories from fat) 1
- For triglycerides ≥2000 mg/dL, implement both drug and non-drug therapies simultaneously 1
- Fenofibrate is indicated as adjunctive therapy to diet 3
Efficacy of Fenofibrate
- Reduces triglyceride levels by 30-50% in patients with hypertriglyceridemia 4, 5
- More effective than omega-3 fatty acids in reducing triglycerides (29% vs 21% reduction) 4
- Recent real-world evidence shows 50.1% reduction in triglycerides after 6 months of treatment 5
- Promotes shift from small, dense atherogenic LDL particles to larger, less dense LDL particles 6
- Also reduces non-HDL cholesterol by 33.7% and CRP by 39% 5
Dosing Considerations
- Initial dose: 54-160 mg daily based on severity and renal function 3
- Renal adjustment:
- Normal/mild-moderate CKD: 96 mg/day
- Moderate CKD (Stage 3): 48 mg/day
- eGFR 30-59 mL/min: ≤54 mg/day
- eGFR <30 mL/min: Avoid use 2
- Take with meals to optimize bioavailability 3
- Monitor lipid levels every 4-8 weeks initially and adjust dose accordingly 3
Important Non-Pharmacological Measures
- Implement low-fat diet before and during fenofibrate treatment 3
- Address excess body weight and alcohol intake 3
- Incorporate regular physical exercise 1
- Treat contributory conditions (diabetes, hypothyroidism) 3
- Consider discontinuing medications that may elevate triglycerides (thiazides, beta-blockers, estrogens) 3
Monitoring and Safety
- Monitor renal function regularly, especially in elderly patients 2, 3
- Assess lipid profile every 4-8 weeks initially, then periodically 3
- Withdraw therapy if inadequate response after 2 months at maximum dose 3
- Avoid in patients with severe renal impairment, active liver disease, or gallbladder disease 2
- When combining with statins, use pravastatin preferentially to minimize myopathy risk 2
Special Populations
- HIV patients: Fenofibrate (200 mg daily) can reduce triglycerides by 54% in patients with HIV on antiretroviral therapy 1
- Diabetic patients: Improving glycemic control may reduce need for pharmacological intervention in patients with fasting chylomicronemia 3
- Patients with NASH: Fenofibrate effectively mitigates hypertriglyceridemia in patients with nonalcoholic steatohepatitis 7
Fenofibrate remains a cornerstone therapy for severe hypertriglyceridemia and an important adjunctive option for moderate hypertriglyceridemia when statins alone are insufficient to achieve lipid goals.