What is the treatment for severe hypertriglyceridemia?

Management of Severe Hypertriglyceridemia with Triglycerides >2000 mg/dL

For patients with triglycerides >2000 mg/dL, immediate treatment should include severe dietary fat restriction (<10% of calories) along with fenofibrate therapy (starting at 54-160 mg daily) to reduce the risk of acute pancreatitis. 1, 2

Initial Management

Immediate Interventions

• Severe dietary fat restriction (<10% of total calories)
• Fenofibrate therapy:
  • Starting dose: 54-160 mg daily
  • Maximum dose: 160 mg daily
  • Take with meals to optimize bioavailability 3
• Optimize glycemic control if diabetes is present (first priority) 2, 1

Lifestyle Modifications

• Dietary changes:

  • Reduce carbohydrate intake, especially refined carbohydrates
  • Increase fiber intake to 10-25g/day
  • Eliminate alcohol consumption
  • Increase omega-3 fatty acids through fish consumption
  • Use extra virgin olive oil as main added fat 1

• Physical activity:

  • Aim for at least 150 minutes per week of moderate-intensity aerobic activity
  • Can reduce triglycerides by approximately 20% 1

• Weight management:

  • Target 5-10% weight loss to reduce triglycerides by approximately 20% 1

Pharmacological Therapy

Primary Medication

• Fenofibrate is the first-line pharmacological therapy for severe hypertriglyceridemia (≥2000 mg/dL) 1, 3
  • Dosing should be individualized according to patient response
  • Evaluate effects after 4-8 weeks and adjust dose if necessary
  • Maximum dose: 160 mg once daily 3

Special Considerations

• Renal impairment:

  • Start with 54 mg/day in mild to moderate renal impairment
  • Avoid in severe renal impairment 3

• Elderly patients:

  • Dose selection based on renal function 3

• Diabetes:

  • Optimize glycemic control as first priority
  • Consider metformin as it may help improve lipid profile 1

Monitoring and Follow-up

• Recheck lipid panels 4-8 weeks after initiating therapy 1
• Monitor liver function tests regularly
• Primary goal: Reduce triglycerides to <500 mg/dL to prevent pancreatitis
• Secondary goal: Achieve triglycerides <150 mg/dL 1

Potential Pitfalls and Caveats

1. Risk of myositis: The combination of statins with fibrates increases the risk of myositis. If combination therapy is needed, fenofibrate is preferred over gemfibrozil when combined with statins 1, 2

2. Secondary causes: Always evaluate for secondary causes of hypertriglyceridemia:

   • Poorly controlled diabetes
   • Hypothyroidism
   • Renal disease
   • Medications (estrogen, thiazide diuretics, beta-blockers)
   • Excessive alcohol intake 1, 3

3. Pregnancy: Fibrates and statins are contraindicated during pregnancy 1

4. Pancreatitis risk: Markedly elevated triglyceride levels (>2,000 mg/dL) significantly increase the risk of developing pancreatitis, although the effect of fenofibrate therapy on reducing this risk has not been adequately studied 3, 4

The evidence strongly supports immediate intervention with dietary fat restriction and fenofibrate therapy for patients with triglycerides >2000 mg/dL, with the primary goal of reducing pancreatitis risk by lowering triglyceride levels below 500 mg/dL as quickly as possible 2, 1, 3.