When and how to treat hypertriglyceridemia?

Treatment of Hypertriglyceridemia: When and How

For hypertriglyceridemia, treatment should be initiated at triglyceride levels ≥500 mg/dL to reduce pancreatitis risk, while levels 150-499 mg/dL warrant treatment based on cardiovascular risk factors, with lifestyle modifications as first-line therapy followed by appropriate pharmacological interventions based on severity. 1, 2

Classification and When to Treat

• Mild hypertriglyceridemia: 150-199 mg/dL
• Moderate hypertriglyceridemia: 200-499 mg/dL
• Severe hypertriglyceridemia: 500-1,999 mg/dL
• Very severe hypertriglyceridemia: ≥2,000 mg/dL 2

Treatment thresholds:

1. Immediate treatment required: TG ≥500 mg/dL - to reduce pancreatitis risk 1
2. Treatment recommended: TG 150-499 mg/dL - to reduce cardiovascular risk, especially with other risk factors 1, 2

Evaluation Before Treatment

• Assess for secondary causes:

  • Diabetes and poor glycemic control
  • Obesity and metabolic syndrome
  • Chronic liver or kidney disease
  • Hypothyroidism
  • Medications (estrogen therapy, thiazide diuretics, beta-blockers)
  • Excessive alcohol consumption 1, 2, 3

• Evaluate for other cardiovascular risk factors and components of metabolic syndrome 2

Treatment Approach

First-Line: Lifestyle Modifications

For all patients with TG >150 mg/dL:

• Diet modifications:

  • For TG 150-499 mg/dL: Fat intake 20-25% of calories, reduce refined carbohydrates
  • For TG 500-999 mg/dL: Further reduce refined carbohydrates, eliminate added sugars
  • For TG ≥1,000 mg/dL: Restrict total fat to 10-15% of daily calories 2
  • Increase soluble fiber (10-25g/day)
  • Add plant stanols/sterols (2g/day)

• Physical activity:

  • At least 150 minutes/week of moderate-intensity or 75 minutes/week of vigorous aerobic activity 2

• Weight management:

  • Target 5-10% weight reduction for overweight/obese patients 2

• Alcohol:

  • Significantly limit or completely avoid alcohol consumption 2

Pharmacological Therapy

For Severe Hypertriglyceridemia (≥500 mg/dL):

1. Fibrates (first-line for isolated hypertriglyceridemia):

   • Fenofibrate: Initial dose 54-160 mg/day, maximum 160 mg/day 3
   • Expected TG reduction: 30-50% 2
   • Dosage should be individualized according to patient response
   • For renal impairment: Start at 54 mg/day 3

2. Prescription omega-3 fatty acids:

   • Dosage: 4g/day
   • Expected TG reduction: 25-35% 2

For Moderate Hypertriglyceridemia (150-499 mg/dL):

1. With elevated LDL-C or cardiovascular risk:

   • Statins (first-line): Expected TG reduction 10-30% 2

2. For patients with ASCVD or other CV risk factors on a statin with controlled LDL but elevated TG:

   • Consider adding icosapent ethyl 1, 2

3. Alternative options:

   • Niacin: Gradually titrated to therapeutic dose
   • Caution: May worsen insulin resistance 2

Combination Therapy Considerations

• Statin plus fibrate: Generally not recommended due to lack of improved ASCVD outcomes 1
• Statin plus niacin: Not recommended due to lack of additional cardiovascular benefit and increased risk of side effects 1
• Statin plus omega-3 fatty acids: May be considered for refractory cases 2

Monitoring and Target Goals

• Monitor triglyceride response after 8-12 weeks of therapy 2
• Monitor liver and renal function with pharmacological therapy, especially with fibrates 2
• Target goals:
  • Triglycerides: <150 mg/dL
  • LDL cholesterol: <100 mg/dL (in high-risk patients)
  • Non-HDL cholesterol: <130 mg/dL 2

Important Precautions

• Combination of statins with fibrates increases risk of myositis (fenofibrate has lower risk than gemfibrozil) 1, 2
• Statins are contraindicated in pregnancy; women of childbearing age should use reliable contraception 2
• Withdraw therapy if inadequate response after two months of maximum recommended dose 3
• For patients with renal impairment, adjust fibrate dosing appropriately 3