What are the treatment options for a patient with hypertriglyceridemia?

Management of Hypertriglyceridemia

Lifestyle modifications are the cornerstone of hypertriglyceridemia management, with pharmacotherapy added based on triglyceride levels and cardiovascular risk. 1

Classification of Hypertriglyceridemia

Triglyceride Level	Classification	Primary Risk
<150 mg/dL	Normal	-
150-499 mg/dL	Mild to Moderate	Cardiovascular disease
500-999 mg/dL	Severe	Pancreatitis + Cardiovascular disease
≥1000 mg/dL	Very Severe	Acute pancreatitis (high risk)

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

• Dietary changes:

  • Reduce saturated fats and eliminate trans fats
  • Limit added sugars to <6% of total daily calories
  • Restrict sugar-sweetened beverages
  • Increase fatty fish consumption (2+ servings/week)
  • Increase dietary fiber intake (>10g/day) 1
  • For severe hypertriglyceridemia (500-999 mg/dL): 20-25% calories from fat
  • For very severe hypertriglyceridemia (≥1000 mg/dL): 10-15% calories from fat 2

• Physical activity:

  • At least 150 minutes/week of moderate-intensity aerobic activity or 75 minutes/week of vigorous activity 1
  • Regular aerobic and resistance training can decrease triglycerides by 6-11% 1

• Weight management:

  • Target 5-10% weight loss if overweight/obese (can decrease triglycerides by 20%) 1
  • Weight loss is considered the most effective lifestyle intervention 2

Step 2: Identify and Address Secondary Causes

• Uncontrolled diabetes (optimize glycemic control)
• Hypothyroidism
• Chronic liver or kidney disease
• Excessive alcohol intake
• Medications that raise triglycerides:
  • Oral estrogens, tamoxifen, raloxifene
  • Beta blockers, thiazide diuretics
  • Immunosuppressive drugs
  • Atypical antipsychotics
  • Retinoids, glucocorticoids 2, 1

Step 3: Pharmacologic Therapy Based on Triglyceride Levels

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

• If ASCVD risk ≥7.5%:
  • First-line: Statin therapy (reduces VLDL and associated risk factors) 2
  • Add-on therapy for persistent elevation despite statin: Icosapent ethyl (4g/day) 1

For Severe Hypertriglyceridemia (≥500 mg/dL):

• First-line: Fibrates (e.g., fenofibrate) to prevent pancreatitis 2, 1, 3

  • Initial dose: 54-160 mg daily with meals
  • Dosage should be individualized according to patient response
  • Monitor lipid levels after 4-8 weeks and adjust dose accordingly 3

• Alternative or add-on therapy: Omega-3 fatty acids 1

  • Prescription icosapent ethyl (purified EPA) has shown cardiovascular benefit 4

• For very severe hypertriglyceridemia (≥1000 mg/dL):

  • Consider extreme dietary fat restriction (<5% of total calories as fat) until triglycerides are ≤1000 mg/dL 2
  • May require combination therapy with fibrates and omega-3 fatty acids 5

Monitoring and Follow-up

• Assess lipid profile after 4-12 weeks of lifestyle interventions
• Reassess after 3-6 months, with annual screening for diabetes if metabolic syndrome is present
• Monitor lipid levels every 4-8 weeks initially after starting medication
• Consider withdrawing therapy if no adequate response after two months of maximum dose 1

Important Considerations

• Risk of pancreatitis: Triglyceride levels >1000 mg/dL significantly increase risk of acute pancreatitis and require immediate intervention 1

• Statin-fibrate combination: Use with caution as this combination may increase risk of myositis 1

• Referral to registered dietitian nutritionist: Strongly recommended for individualized nutrition recommendations, especially for severe hypertriglyceridemia 2

• Medication selection cautions:

  • Avoid fenofibrate in patients with severe renal impairment
  • Avoid fenofibrate in patients with preexisting gallbladder disease
  • Start at lower doses (54 mg/day) in patients with mild to moderate renal impairment 3

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