How to manage hypertriglyceridemia?

Management of Hypertriglyceridemia

The management of hypertriglyceridemia should begin with lifestyle modifications as first-line therapy, followed by appropriate pharmacotherapy based on triglyceride levels and cardiovascular risk, with fibrates being the first-line medication for severe hypertriglyceridemia (≥500 mg/dL) to prevent pancreatitis. 1, 2

Classification of Hypertriglyceridemia

Triglyceride levels are classified as:

• 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, 2

Initial Evaluation

• Assess for secondary causes: excessive alcohol intake, uncontrolled diabetes, hypothyroidism, renal/liver disease, pregnancy, medications (thiazides, beta-blockers, estrogen, isotretinoin, corticosteroids, antiretrovirals, antipsychotics) 1
• Evaluate for family history of dyslipidemia and cardiovascular disease
• Screen for other cardiovascular risk factors: central obesity, hypertension, abnormal glucose metabolism, liver dysfunction 1

Management Approach

1. Lifestyle Modifications (First-Line for All Patients)

• Dietary changes:

  • For TG 150-499 mg/dL: Restrict added sugars to <6% and total fat to 30-35% of daily calories
  • For TG 500-999 mg/dL: Restrict added sugars to <5% and total fat to 20-25% of daily calories
  • For TG ≥1000 mg/dL: Eliminate added sugars and restrict total fat to 10-15% of daily calories 2
  • Reduce refined carbohydrates and increase omega-3 rich foods 2
  • Increase dietary fiber to >10g/day 2

• Physical activity:

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

• Alcohol restriction:

  • Limitation for TG 150-499 mg/dL
  • Complete abstinence for TG ≥500 mg/dL 2

• Weight management for overweight/obese patients 1, 2

2. Pharmacotherapy

For Severe Hypertriglyceridemia (≥500 mg/dL)

• Fibrates (e.g., fenofibrate) are first-line treatment to reduce pancreatitis risk 1, 2

  • Initial dose: 54-160 mg/day, individualized according to patient response
  • Maximum dose: 160 mg once daily 3
  • Monitor lipid levels every 4-8 weeks initially 2

• Prescription omega-3 fatty acids (4g/day) can be considered 2

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

• Statins are first-line for patients with established ASCVD, diabetes, or elevated cardiovascular risk 2, 4

  • Statins typically provide 10-15% reduction in triglyceride levels 1

• For patients with residual risk despite statin therapy:

  • Consider adding icosapent ethyl (purified EPA) 4g/day for patients with established ASCVD or diabetes with additional risk factors 2, 4
  • The REDUCE-IT trial demonstrated significant cardiovascular benefit with icosapent ethyl in high-risk patients 1, 4

• Treatment goal for moderate hypertriglyceridemia: non-HDL cholesterol level of 30 mg/dL higher than the LDL goal 1

3. Special Considerations

• Renal impairment: Start fenofibrate at 54 mg/day in mild to moderate renal impairment; avoid in severe renal impairment 3

• Elderly patients: Dose selection based on renal function 3

• Combination therapy: May be necessary for patients with elevated LDL-C and high cardiovascular risk 2

  • Caution with statin-fibrate combinations due to increased risk of myositis 2

Monitoring and Follow-up

• Assess response to lifestyle interventions after 4-12 weeks 2
• Monitor lipid levels every 4-8 weeks initially if pharmacotherapy is initiated 2
• Once goals are achieved, follow-up every 6-12 months 2
• Consider discontinuing therapy if no adequate response after two months of maximum dose 3

Important Clinical Pearls

1. Pancreatitis risk increases significantly when triglyceride levels exceed 500 mg/dL, with highest risk at ≥1000 mg/dL 2

2. Secondary causes should be addressed before or alongside pharmacotherapy 1, 3

3. Safety considerations:

   • Omega-3 fatty acids may increase bleeding risk with anticoagulants/antiplatelets 2
   • Statin-fibrate combinations increase myositis risk 2
   • Fenofibrate is contraindicated in severe renal impairment, active liver disease, preexisting gallbladder disease, and nursing mothers 3

4. Referral to a registered dietitian is strongly recommended for individualized nutrition recommendations 1

By following this structured approach to hypertriglyceridemia management, clinicians can effectively reduce the risk of pancreatitis in patients with severe hypertriglyceridemia and decrease cardiovascular risk in those with moderate hypertriglyceridemia.