What is the treatment for hypertriglyceridemia?

Treatment of High Triglycerides

The treatment of hypertriglyceridemia depends critically on the severity level: for triglycerides ≥500 mg/dL, immediately initiate fenofibrate (54-160 mg daily) to prevent acute pancreatitis; for moderate levels (200-499 mg/dL), prioritize lifestyle modifications and consider statins if LDL-C is elevated or cardiovascular risk is high; for mild elevations (150-199 mg/dL), focus on lifestyle changes and address secondary causes. 1, 2

Classification and Risk Assessment

The American College of Cardiology classifies hypertriglyceridemia as follows: 1, 2

• Normal: <150 mg/dL
• Mild: 150-199 mg/dL
• Moderate: 200-499 mg/dL
• Severe: 500-999 mg/dL
• Very severe: ≥1,000 mg/dL

Before initiating any treatment, evaluate for secondary causes including excessive alcohol intake, uncontrolled diabetes, hypothyroidism, renal disease, liver disease, and medications (thiazides, beta-blockers, estrogen, corticosteroids). 1, 2, 3

Lifestyle Interventions (Foundation for All Levels)

Weight loss is the single most effective intervention, with a 5-10% reduction producing up to 20% decrease in triglycerides. 1, 2

Dietary Modifications by Severity:

For mild to moderate hypertriglyceridemia (150-499 mg/dL): 1, 2

• Restrict added sugars to <6% of total daily calories
• Limit total fat to 30-35% of total daily calories
• Eliminate trans fats completely

For severe hypertriglyceridemia (500-999 mg/dL): 1, 2

• Restrict added sugars to <5% of total calories
• Limit total fat to 20-25% of total daily calories
• Complete alcohol abstinence is mandatory

For very severe hypertriglyceridemia (≥1,000 mg/dL): 1, 2

• Eliminate all added sugars completely
• Restrict total fat to 10-15% of daily calories (or even <5% until levels drop below 1,000 mg/dL)
• Absolute alcohol prohibition

Exercise Requirements:

Engage in at least 150 minutes/week of moderate-intensity or 75 minutes/week of vigorous aerobic activity, which reduces triglycerides by approximately 11%. 1, 2

Pharmacologic Therapy Algorithm

For Severe to Very Severe Hypertriglyceridemia (≥500 mg/dL):

Fibrates are first-line therapy to prevent acute pancreatitis. 1, 2, 3

• Fenofibrate dosing: Start 54-160 mg daily with meals (optimizes bioavailability) 3
• Provides 30-50% triglyceride reduction 1, 2
• Critical priority: Reduce triglycerides below 500 mg/dL before focusing on LDL-C goals 1, 2
• Monitor lipid levels at 4-8 week intervals after initiation 3
• Withdraw therapy if no adequate response after 2 months at maximum dose (160 mg daily) 3

Important caveat: In patients with renal impairment, start at 54 mg daily and increase only after evaluating renal function and lipid response. Avoid fenofibrate entirely in severe renal impairment. 3

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

Statins are preferred if LDL-C is elevated or cardiovascular risk is increased. 1, 2

• Statins provide 10-30% dose-dependent triglyceride reduction 1, 2
• Target non-HDL-C <130 mg/dL 2
• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, add prescription omega-3 fatty acids (icosapent ethyl 2-4 g/day) 1, 2

For Mild Hypertriglyceridemia (150-199 mg/dL):

Focus on lifestyle modifications and address secondary causes. 1, 2

Consider statin therapy if 10-year ASCVD risk is ≥7.5% or if persistently elevated nonfasting triglycerides ≥175 mg/dL with other cardiovascular risk factors. 2

Prescription Omega-3 Fatty Acids

Icosapent ethyl (2-4 g/day) is indicated as adjunctive therapy for patients with: 1, 2

• Triglycerides ≥150 mg/dL on maximally tolerated statin therapy
• Established cardiovascular disease OR diabetes with ≥2 additional risk factors
• Persistent elevation >200 mg/dL after 3 months of lifestyle optimization

Monitor for increased risk of atrial fibrillation with omega-3 therapy. 2

Special Considerations

Diabetes Management:

Optimizing glycemic control is often more effective than additional lipid medications in diabetic patients with severe hypertriglyceridemia, as poor glucose control is frequently the primary driver. 1, 2

Combination Therapy Safety:

When combining fibrates with statins, use lower statin doses to minimize myopathy risk, particularly in patients >65 years or with renal disease. 1, 2 Fenofibrate has a better safety profile than gemfibrozil when combined with statins. 1

Monitor creatine kinase levels and muscle symptoms when using combination therapy. 2

Common Pitfalls to Avoid

• Do not delay fibrate initiation while attempting lifestyle modifications alone when triglycerides are ≥500 mg/dL—pharmacologic therapy is mandatory to prevent pancreatitis 1, 2
• Do not start with statin monotherapy when triglycerides are ≥500 mg/dL, as statins provide insufficient triglyceride reduction at this level 2
• Do not use bile acid sequestrants when triglycerides are >200 mg/dL, as they are relatively contraindicated 2
• Do not substitute over-the-counter fish oil for prescription omega-3 formulations—they are not equivalent 2

Monitoring and Follow-up

Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications or starting pharmacotherapy. 1, 4 Once goals are achieved, follow-up every 6-12 months. 2