What are the treatment options for hypertriglyceridemia?

Treatment Options for Hypertriglyceridemia

The treatment of hypertriglyceridemia should begin with lifestyle modifications for all patients, with pharmacologic therapy added based on triglyceride severity levels, with fibrates being first-line therapy for severe hypertriglyceridemia (≥500 mg/dL) and statins preferred for moderate hypertriglyceridemia with elevated cardiovascular risk. 1, 2

Classification of Hypertriglyceridemia

• Normal: <150 mg/dL 2
• Mild: 150-199 mg/dL 2
• Moderate: 200-499 mg/dL 2, 3
• Severe: 500-999 mg/dL 2, 3
• Very severe: ≥1000 mg/dL 2, 3

Initial Assessment

• Evaluate for secondary causes before initiating treatment: 2, 3
  • Excessive alcohol intake
  • Uncontrolled diabetes
  • Hypothyroidism
  • Renal disease
  • Liver disease
  • Medications (thiazides, beta-blockers, estrogen, corticosteroids)
• Assess cardiovascular risk factors including family history, central obesity, hypertension, and abnormal glucose metabolism 2
• Determine risk of pancreatitis, particularly with triglycerides ≥500 mg/dL 2

First-Line Treatment: Lifestyle Interventions

• Weight loss is the most effective lifestyle intervention: 1, 2, 3

  • Target 5-10% weight loss, which can reduce triglycerides by 20%
  • Some patients may experience up to 50-70% reduction in triglycerides with weight loss

• Dietary modifications: 1, 2, 3

  • For mild to moderate hypertriglyceridemia: Restrict added sugars to <6% of total daily calories and limit total fat to 30-35% of total daily calories
  • For severe hypertriglyceridemia (500-999 mg/dL): Further restrict added sugars to <5% and total fat to 20-25% of total daily calories
  • For very severe hypertriglyceridemia (≥1000 mg/dL): Eliminate added sugars and restrict total fat to 10-15% of daily calories

• Physical activity: 2, 3

  • Engage in at least 150 minutes/week of moderate-intensity or 75 minutes/week of vigorous aerobic activity

• Alcohol consumption: 2, 3

  • Limit or completely avoid alcohol consumption, especially in patients with severe hypertriglyceridemia

Pharmacologic Therapy

For Severe Hypertriglyceridemia (≥500 mg/dL)

• Fibrates are first-line drug therapy to reduce the risk of pancreatitis: 2, 4

  • Initial dose of fenofibrate is 54 mg to 160 mg per day
  • Dosage should be individualized according to patient response
  • Maximum dose is 160 mg once daily
  • Dose adjustments needed for renal impairment

• Prescription omega-3 fatty acids: 1, 2

  • Can be used as adjunctive therapy for severe hypertriglyceridemia
  • Icosapent ethyl (EPA) is FDA-approved for cardiovascular risk reduction in patients with elevated triglycerides (≥150 mg/dL) with established cardiovascular disease or diabetes with ≥2 additional risk factors

For Moderate Hypertriglyceridemia (200-499 mg/dL)

• Statins are preferred if there is elevated LDL-C or increased cardiovascular risk: 2, 3

  • Can provide 10-30% reduction in triglycerides

• If triglycerides remain elevated after statin therapy, consider adding: 1, 2

  • Prescription omega-3 fatty acids (2-4g/day)
  • Fenofibrate as add-on therapy if triglycerides remain significantly elevated and cardiovascular risk is high

Special Considerations

• Optimize glycemic control in patients with diabetes, as it can significantly improve triglyceride levels 2
• Monitor for increased risk of atrial fibrillation with prescription omega-3 fatty acids 1, 2
• Avoid bile acid sequestrants if triglycerides are >200 mg/dL 2
• Monitor for potential myopathy risk when combining fibrates with statins, especially in patients >65 years of age 2

Monitoring and Follow-up

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications 2, 3
• Consider withdrawing therapy if no adequate response after two months of treatment with maximum recommended dose 4

Treatment Algorithm

1. For all patients: Implement appropriate lifestyle modifications 1, 2, 3
2. For triglycerides ≥500 mg/dL: Start fibrate therapy immediately to reduce pancreatitis risk 2, 4
3. For triglycerides 200-499 mg/dL with elevated cardiovascular risk: Start statin therapy 2, 3
4. For triglycerides 200-499 mg/dL that remain elevated despite statin therapy: Consider adding omega-3 fatty acids or fenofibrate 1, 2
5. For patients with diabetes: Optimize glycemic control 2