What is the treatment for hypertriglyceridemia?

Treatment for Hypertriglyceridemia

The treatment of hypertriglyceridemia should begin with lifestyle modifications, followed by statin therapy for cardiovascular risk reduction, with additional triglyceride-lowering medications such as fibrates or prescription omega-3 fatty acids added based on triglyceride severity and pancreatitis risk. 1

Classification and Initial Assessment

Hypertriglyceridemia severity can be classified as:

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

Before initiating pharmacologic therapy, it's essential to:

• Identify and address secondary causes of hypertriglyceridemia
• Assess cardiovascular risk and pancreatitis risk

Secondary Causes to Identify and Address

• Medical conditions: Diabetes mellitus (especially poor glycemic control), hypothyroidism, chronic liver or kidney disease, nephrotic syndrome 1
• Medications: Beta-blockers, thiazide diuretics, retinoids, antipsychotics, estrogens 1
• Lifestyle factors: Excessive alcohol consumption, high-carbohydrate diet, obesity 1

Treatment Algorithm

Step 1: Lifestyle Modifications (First-Line for All Patients)

• Diet modifications:

  • Eliminate added sugars and refined carbohydrates
  • Increase soluble fiber (>10g/day)
  • Consume fatty fish twice weekly
  • For severe hypertriglyceridemia (≥1,000 mg/dL): Very low-fat diet (10-15% of calories) 2
  • For extremely high levels: <5% of total calories as fat until TG <1,000 mg/dL 2

• Weight reduction: Target 5-10% weight loss (can achieve 20% TG reduction) 1

• Exercise: 150 minutes/week of moderate-intensity aerobic activity 1

• Alcohol elimination: Particularly important in hypertriglyceridemia 2, 1

Step 2: Pharmacologic Therapy Based on TG Levels

For Moderate Hypertriglyceridemia (200-499 mg/dL):

1. Statin therapy (first-line pharmacologic treatment):

   • Provides 10-30% TG reduction
   • Indicated when elevated LDL-C or cardiovascular risk present 1
   • Target LDL-C <100 mg/dL (or <70 mg/dL if cardiovascular disease is present) 1

2. If TG remains elevated on statin therapy:

   • Add prescription omega-3 fatty acids (4g/day) - reduces TG by 25-35% 1
   • Icosapent ethyl can be considered in patients with ASCVD or other cardiovascular risk factors 1

For Severe Hypertriglyceridemia (≥500 mg/dL):

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

   • Provides 35-50% TG reduction 1
   • Initial dose for severe hypertriglyceridemia: 54-160 mg/day, adjusted based on response 3
   • Maximum dose: 160 mg once daily 3

2. If inadequate response:

   • Combination therapy with fibrate plus omega-3 fatty acids 2
   • Monitor for potential side effects, especially with statin-fibrate combinations 1

Special Considerations

Diabetes

• Optimize glycemic control first, then reassess triglyceride levels 2, 1
• With insulin insufficiency and markedly elevated TG, treat hyperglycemia first 2

Renal Impairment

• For mild to moderate renal impairment: Start fenofibrate at 54 mg/day 3
• Avoid fenofibrate in severe renal impairment 3

Pregnancy

• Statins are contraindicated in pregnancy 1
• Women of childbearing age should use reliable contraception when on statin therapy 1

Monitoring

• Check lipid levels after 8-12 weeks of therapy 1
• Monitor liver and renal function with pharmacological therapy, especially with fibrates 1
• Target goals:
  • Primary goal: Reduce TG <500 mg/dL to prevent pancreatitis 1
  • Final goal: TG <150 mg/dL 1
  • LDL-C <100 mg/dL
  • Non-HDL-C <130 mg/dL

Potential Pitfalls

• Statin-fibrate combination risks: Increased risk of myopathy and rhabdomyolysis, particularly with gemfibrozil (fenofibrate has lower risk) 1
• Omega-3 products containing DHA: May increase LDL-C levels 1
• Inadequate lifestyle modification: Pharmacologic therapy will have limited efficacy without addressing underlying lifestyle factors 2, 1
• Overlooking secondary causes: Treating the medication without addressing the underlying cause will yield suboptimal results 1, 3