What is the treatment for hypertriglyceridemia?

Treatment of Hypertriglyceridemia

The treatment of hypertriglyceridemia requires a stepwise approach starting with lifestyle modifications as first-line therapy, followed by pharmacological interventions based on triglyceride severity levels, with the primary goal of reducing triglycerides below 500 mg/dL to prevent pancreatitis. 1

Classification and Treatment Goals

Hypertriglyceridemia is classified into several categories:

• Normal: <150 mg/dL
• Borderline high: 150-199 mg/dL
• High: 200-499 mg/dL
• Very high: ≥500 mg/dL
• Severe: 1000-1999 mg/dL
• Very severe: ≥2000 mg/dL 1

Treatment goals:

• Primary goal: Reduce TG levels <500 mg/dL to prevent pancreatitis
• Final goal: Reduce TG levels to <150 mg/dL 1

First-Line Treatment: Lifestyle Modifications

Lifestyle modifications should be implemented before pharmacological therapy:

1. Dietary modifications:

   • Eliminate added sugars and refined carbohydrates
   • Increase soluble fiber (>10g/day)
   • Consume fatty fish twice weekly
   • Follow specific diet based on TG levels:
     • Moderate-fat diet for TG 150-499 mg/dL
     • Low-fat diet for TG 500-999 mg/dL
     • Very-low-fat diet for TG ≥1,000 mg/dL 1

2. Weight reduction:

   • Target 5-10% weight reduction (can reduce TG by approximately 20%)
   • Regular aerobic exercise (150 minutes/week of moderate-intensity activity) 1

3. Address secondary causes:

   • Optimize glycemic control in diabetes
   • Reduce alcohol consumption
   • Review medications that may exacerbate hypertriglyceridemia:
     • Beta-blockers
     • Thiazide diuretics
     • Retinoids
     • Antipsychotics
     • Estrogens (oral contraceptives, hormone replacement therapy) 1

Pharmacological Treatment

For TG 150-499 mg/dL with elevated LDL-C or cardiovascular risk:

1. Statins (first-line):

   • Provide 10-30% dose-dependent reduction in TG
   • Target LDL-C <100 mg/dL (or <70 mg/dL if cardiovascular disease is present) 1

2. Add-on therapy if goals not achieved with statins:

   • Prescription omega-3 fatty acids (4g/day) - reduce TG by 25-35% 1
   • Icosapent ethyl for patients with ASCVD or other cardiovascular risk factors on statin with controlled LDL-C but persistent TG 150-499 mg/dL 1

For TG ≥500 mg/dL (primary goal is to prevent pancreatitis):

1. Fibrates (e.g., fenofibrate 54-160 mg daily):

   • Provide 35-50% TG reduction
   • Initial dose for severe hypertriglyceridemia: 54-160 mg/day
   • Maximum dose: 160 mg once daily
   • Adjust dose based on response after 4-8 weeks 1, 2

2. Combination therapy if needed:

   • Statin + fibrate (increased risk of myopathy, monitor carefully)
   • Statin + omega-3 fatty acids 1

Special Considerations

Renal Impairment

• For mild to moderate renal impairment: Start fenofibrate at 54 mg/day
• Avoid fenofibrate in severe renal impairment 2

Monitoring

• Check triglyceride response after 8-12 weeks of therapy
• Monitor for potential increases in LDL-C levels with omega-3 fatty acids
• Monitor liver and renal function with pharmacological therapy, especially with fibrates
• Watch for muscle symptoms, especially with statin-fibrate combinations 1

Contraindications

• Fenofibrate is contraindicated in:
  • Severe renal impairment including dialysis
  • Active liver disease
  • Preexisting gallbladder disease
  • Nursing mothers
  • Known hypersensitivity to fenofibrate or fenofibric acid 2
• Statins are contraindicated in pregnancy 1

Common Pitfalls to Avoid

1. Failure to address secondary causes before initiating pharmacological therapy
2. Not optimizing glycemic control in patients with diabetes before assessing need for lipid-lowering therapy
3. Inadequate monitoring for adverse effects, especially with combination therapy
4. Starting with high-dose medications before maximizing lifestyle modifications
5. Not adjusting therapy based on triglyceride response after 8-12 weeks

By following this structured approach to hypertriglyceridemia management, clinicians can effectively reduce triglyceride levels, prevent pancreatitis in severe cases, and potentially reduce cardiovascular risk.