What is the next step in management for a patient with a lipid panel showing total cholesterol 221 mg/dL, high‑density lipoprotein (HDL) cholesterol 37 mg/dL, triglycerides 514 mg/dL (non‑fasting), low‑density lipoprotein (LDL) cholesterol not calculated, cholesterol/HDL ratio 6.0, and non‑HDL cholesterol 184 mg/dL?

Next Steps in Management

Immediately initiate fenofibrate 54–160 mg daily to prevent acute pancreatitis, while simultaneously implementing extreme dietary fat restriction (<20–25% of calories), complete elimination of added sugars and alcohol, and urgent evaluation for secondary causes—particularly uncontrolled diabetes and hypothyroidism. 1

Immediate Pharmacologic Intervention

• Start fenofibrate immediately as first-line therapy because triglycerides of 514 mg/dL place this patient at significant risk for acute pancreatitis (14% incidence in severe hypertriglyceridemia), and fibrates provide 30–50% triglyceride reduction regardless of LDL-C levels or cardiovascular risk. 1
• Do not start with statin monotherapy when triglycerides are ≥500 mg/dL, as statins provide only 10–30% triglyceride reduction—insufficient for preventing pancreatitis at this level. 1
• The calculated LDL-C is invalid because the Friedewald equation cannot be used when triglycerides exceed 400 mg/dL; direct LDL measurement will be needed once triglycerides fall below 400 mg/dL. 2, 3

Critical Dietary Interventions (Start Immediately)

• Restrict total dietary fat to 20–25% of total daily calories for severe hypertriglyceridemia (500–999 mg/dL range). 1
• Eliminate all added sugars completely because sugar intake directly increases hepatic triglyceride production. 1
• Abstain completely from all alcohol consumption because even 1 ounce daily increases triglycerides by 5–10%, and alcohol can precipitate hypertriglyceridemic pancreatitis at this level. 1
• Increase soluble fiber intake to >10 g/day from sources like oats, beans, and vegetables. 1

Urgent Assessment for Secondary Causes

• Check hemoglobin A1c and fasting glucose immediately because uncontrolled diabetes is often the primary driver of severe hypertriglyceridemia, and optimizing glucose control can reduce triglycerides by 20–50% independent of lipid medications. 1
• Measure TSH to rule out hypothyroidism, which must be treated before expecting full response to lipid-lowering therapy. 1, 4
• Obtain detailed alcohol history to confirm complete abstinence, as alcohol synergistically worsens hypertriglyceridemia. 1
• Review all medications for agents that raise triglycerides (thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, antipsychotics) and discontinue or substitute if possible. 1
• Assess renal function (creatinine, eGFR) and liver function (AST, ALT) because chronic kidney disease and liver disease contribute to hypertriglyceridemia and affect fenofibrate dosing. 1

Sequential Treatment Algorithm

• Once triglycerides fall below 500 mg/dL (typically 4–8 weeks after fenofibrate initiation), reassess LDL-C with direct measurement and consider adding statin therapy if LDL-C is elevated or cardiovascular risk is high. 1
• Target LDL-C <100 mg/dL (or <70 mg/dL for very high-risk patients) and non-HDL-C <130 mg/dL once triglycerides are controlled. 2, 1
• If triglycerides remain >200 mg/dL after 3 months of fenofibrate plus optimized lifestyle modifications, add prescription omega-3 fatty acids (icosapent ethyl 2–4 g daily) as adjunctive therapy. 1

Monitoring Strategy

• Reassess fasting lipid panel in 4–8 weeks after implementing dietary modifications and fenofibrate to evaluate response. 1
• Monitor renal function at baseline, at 3 months, and then every 6 months while on fenofibrate, as the drug is substantially excreted by the kidney. 1
• Watch for muscle symptoms and obtain baseline and follow-up creatine kinase (CK) levels, especially if combining fenofibrate with a statin in the future. 1

Treatment Goals

• Primary goal: Reduce triglycerides to <500 mg/dL to eliminate pancreatitis risk. 1
• Secondary goal: Further reduce triglycerides to <200 mg/dL (ideally <150 mg/dL) to reduce cardiovascular risk. 1
• Tertiary goal: Achieve non-HDL-C <130 mg/dL once triglycerides are controlled. 2, 1

Critical Pitfalls to Avoid

• Do not delay fenofibrate initiation while attempting lifestyle modifications alone—pharmacologic therapy is mandatory at this triglyceride level to prevent pancreatitis. 1
• Do not overlook secondary causes (uncontrolled diabetes, hypothyroidism, excess alcohol, offending medications), as correcting these can lower triglycerides by 20–50% and may be more effective than additional medications. 1
• Do not use gemfibrozil if combining with a statin in the future; fenofibrate has a significantly better safety profile with lower myopathy risk. 1, 5
• Do not rely on calculated LDL-C when triglycerides exceed 400 mg/dL—the Friedewald equation is invalid and direct LDL measurement will be required. 2, 3