What are the treatment options for hypertriglyceridemia?

Treatment Options for Hypertriglyceridemia

For hypertriglyceridemia, treatment should begin with lifestyle modifications, followed by pharmacotherapy with fibrates as first-line medication for severe hypertriglyceridemia (≥500 mg/dL), while statins are preferred for mild-to-moderate hypertriglyceridemia with elevated LDL-C. 1

Classification of Hypertriglyceridemia

• Normal: <150 mg/dL
• Mild: 150-199 mg/dL
• Moderate: 200-499 mg/dL
• Severe: 500-999 mg/dL
• Very severe: ≥1000 mg/dL 1

Step 1: Lifestyle Modifications (First-line for all patients)

• Diet modifications:

  • Very-low-fat diet (10-15% of calories from fat) 1
  • For triglycerides ≥500 mg/dL: Limit added sugars to <5% of calories 1
  • For triglycerides ≥1000 mg/dL: Extreme dietary fat restriction (<5% of calories) until levels decrease below 1000 mg/dL 1
  • Replace refined grains with fiber-rich whole grains 1
  • Choose whole fruits over fruit juices 1
  • Avoid sugar-sweetened beverages 1
  • Include 1-2 seafood meals per week 1

• Physical activity:

  • At least 150 minutes per week of moderate-intensity aerobic activity (can decrease triglycerides by ~11%) 1
  • Include resistance training (can decrease triglycerides by ~6%) 1

• Other important lifestyle changes:

  • Weight loss if overweight/obese (5-10% weight reduction can lower TG by ~20%) 1, 2
  • Complete alcohol abstinence (especially for high-risk individuals) 1
  • Smoking cessation 1

Step 2: Address Secondary Causes

• Evaluate and treat underlying conditions:
  • Optimize glycemic control in diabetes 3, 1
  • Treat hypothyroidism 1
  • Address renal or liver disease 1
  • Review medications that may elevate triglycerides:
    • Thiazides, beta-blockers, estrogen, isotretinoin, corticosteroids, antiretroviral protease inhibitors, antipsychotics 1

Step 3: Pharmacotherapy Based on Triglyceride Levels

For Severe Hypertriglyceridemia (≥500 mg/dL)

• Primary goal: Reduce triglyceride levels to <500 mg/dL to prevent pancreatitis 1, 4
• First-line medication: Fibrates (fenofibrate)
  • Initial dose: 54-160 mg per day 5
  • Maximum dose: 160 mg once daily 5
  • Dosage should be individualized according to patient response 5
  • Monitor lipid levels every 4-8 weeks until stabilized, then every 3 months 1
  • For renal impairment: Start at 54 mg/day in mild to moderate impairment; avoid in severe impairment 5

For Mild to Moderate Hypertriglyceridemia (150-499 mg/dL)

• If elevated LDL-C is also present:

  • First choice: High-dose statin 3
  • For combined hyperlipidemia:
    1. Improved glycemic control plus high-dose statin 3
    2. If inadequate response: Statin plus fibrate (preferably fenofibrate) 3
    3. If still inadequate: Statin plus nicotinic acid 3

• If isolated hypertriglyceridemia:

  • Consider fibrates as initial drug therapy 4
  • Prescription omega-3 fatty acids (4 g/day) may be considered 1

Special Considerations and Cautions

Combination Therapy Risks

• Statin + fibrate combinations:
  • Increased risk of myositis, especially with gemfibrozil 3, 1
  • Fenofibrate has lower risk than gemfibrozil when combined with statins 1
  • Monitor creatine phosphokinase levels 3

Monitoring

• Monitor triglyceride levels every 4-8 weeks until stabilized, then every 3 months 1
• Consider discontinuing therapy if no adequate response after 2 months at maximum dose 5

Acute Pancreatitis Management

• For very severe hypertriglyceridemia (>1000 mg/dL) with pancreatitis risk:
  • More aggressive intervention is needed 1
  • Consider plasmapheresis for rapid triglyceride reduction in cases >2000 mg/dL 1
  • Intravenous insulin (with or without heparin) may be used with careful monitoring 1

Pregnancy Considerations

• Conduct pregnancy tests before starting treatment 1
• Ensure contraception during treatment and for 3 years after discontinuation 1
• Absolute alcohol restriction in women of childbearing potential 1

The treatment of hypertriglyceridemia requires a systematic approach that addresses both the elevated triglyceride levels and associated cardiovascular risk factors. By following this algorithm and individualizing treatment based on triglyceride levels and comorbidities, clinicians can effectively manage hypertriglyceridemia and reduce the risk of complications.