What is the treatment for hypertriglyceridemia (elevated triglycerides)?

Treatment of Hypertriglyceridemia

For severe to very severe hypertriglyceridemia (≥500 mg/dL), initiate fenofibrate 54-160 mg daily immediately to prevent acute pancreatitis, regardless of cardiovascular risk; for moderate hypertriglyceridemia (200-499 mg/dL), prioritize lifestyle modifications and statins if cardiovascular risk is elevated, adding prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) only if triglycerides remain >200 mg/dL after 3 months of optimized therapy. 1, 2, 3

Classification and Risk Assessment

Hypertriglyceridemia severity determines treatment urgency: 1, 2, 3

• Normal: <150 mg/dL
• Mild: 150-199 mg/dL (cardiovascular risk-enhancing factor)
• Moderate: 200-499 mg/dL (increased cardiovascular risk)
• Severe: 500-999 mg/dL (pancreatitis risk begins)
• Very Severe: ≥1,000 mg/dL (high pancreatitis risk)

Before initiating any treatment, aggressively evaluate and address secondary causes: uncontrolled diabetes mellitus (often the primary driver of severe hypertriglyceridemia), hypothyroidism, excessive alcohol intake, chronic kidney disease, liver disease, and medications (thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, antipsychotics). 1, 2, 3

Lifestyle Interventions (Foundation for All Levels)

Weight Loss and Physical Activity

• Target 5-10% body weight reduction, which produces a 20% decrease in triglycerides (in some patients up to 50-70% reduction). 1, 2, 3
• Engage in ≥150 minutes/week of moderate-intensity aerobic activity (or 75 minutes/week vigorous activity), which reduces triglycerides by approximately 11%. 1, 2

Dietary Modifications by Severity Level

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

• Restrict added sugars to <6% of total daily calories (sugar intake directly increases hepatic triglyceride production)
• Limit total fat to 30-35% of total daily calories
• Restrict saturated fats to <7% of total energy intake, replacing with polyunsaturated or monounsaturated fats
• Eliminate trans fatty acids completely

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

• Restrict added sugars to <5% of total daily calories
• Limit total fat to 20-25% of total daily calories

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

• Eliminate all added sugars completely
• Restrict total fat to 10-15% of daily calories (in some cases <5% until triglycerides fall below 1,000 mg/dL)

Alcohol and Other Dietary Factors

• Complete abstinence from alcohol is mandatory for patients with severe hypertriglyceridemia (≥500 mg/dL) to prevent hypertriglyceridemic pancreatitis; even 1 ounce daily increases triglycerides by 5-10% in others. 1, 2, 3
• Consume ≥2 servings per week of fatty fish (salmon, trout, sardines) rich in EPA and DHA. 1
• Increase soluble fiber to >10g/day. 1

Pharmacologic Therapy Algorithm

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

Immediate intervention required to prevent acute pancreatitis: 1, 2, 3, 4

1. Initiate fenofibrate 54-160 mg daily immediately as first-line therapy (provides 30-50% triglyceride reduction). Do NOT delay for lifestyle modifications alone—pharmacologic therapy is mandatory at this level. 1, 2, 3, 4

2. Implement extreme dietary fat restriction (<5-15% of total calories) and eliminate all added sugars and alcohol completely. 1, 2

3. Aggressively optimize glycemic control in diabetic patients, as poor glucose control is often the primary driver of severe hypertriglyceridemia and can dramatically reduce triglycerides independent of lipid medications. 1, 3

4. Once triglycerides fall below 500 mg/dL, reassess LDL-C and consider adding statin therapy if LDL-C is elevated or cardiovascular risk is high. 1, 3

5. If triglycerides remain elevated after fenofibrate and lifestyle optimization, add prescription omega-3 fatty acids (2-4g daily) as adjunctive therapy. 1, 2

Critical pitfall: Do NOT start with statin monotherapy when triglycerides are ≥500 mg/dL—statins provide only 10-30% triglyceride reduction and are insufficient for preventing pancreatitis at this level. 1

For Moderate Hypertriglyceridemia (200-499 mg/dL)

Treatment prioritization depends on cardiovascular risk and LDL-C levels: 1, 2, 3

1. If 10-year ASCVD risk ≥7.5% OR elevated LDL-C: Initiate moderate-to-high intensity statin therapy (atorvastatin 10-40 mg or rosuvastatin 5-20 mg daily), which provides 10-30% dose-dependent triglyceride reduction plus proven cardiovascular benefit. 1, 3

2. Implement aggressive lifestyle modifications (5-10% weight loss, restrict added sugars to <6% of calories, limit fat to 30-35% of calories, eliminate alcohol or limit significantly). 1, 2

3. Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications. 1, 2, 3

4. If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, consider adding prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) specifically for patients with: 1, 3

   • Established cardiovascular disease, OR
   • Diabetes with ≥2 additional risk factors

5. Alternative to omega-3 fatty acids: Consider fenofibrate 54-160 mg daily if icosapent ethyl criteria are not met, though combination statin-fibrate therapy increases myopathy risk (particularly in patients >65 years or with renal disease). 1, 3

Secondary lipid target: Non-HDL-C (total cholesterol minus HDL-C) should be <130 mg/dL for moderate hypertriglyceridemia. 1, 3

For Mild Hypertriglyceridemia (150-199 mg/dL)

Persistently elevated nonfasting triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor: 1

1. If 10-year ASCVD risk ≥7.5%: Consider initiating moderate-intensity statin therapy. 1

2. If 10-year ASCVD risk 5% to <7.5%: Engage in patient-clinician discussion regarding statin initiation. 1

3. Prioritize lifestyle modifications as primary intervention (weight loss, dietary changes, exercise, alcohol reduction). 1, 2

Special Considerations and Safety

Combination Therapy Safety

• When combining fenofibrate with statins, use lower statin doses (atorvastatin 10-20 mg maximum) to minimize myopathy risk, particularly in patients >65 years or with renal disease. 1, 3
• Fenofibrate is preferred over gemfibrozil when combining with statins—gemfibrozil has significantly higher myopathy risk and should be avoided. 1, 3
• Monitor creatine kinase levels and muscle symptoms at baseline and during combination therapy. 1, 3

Icosapent Ethyl (Prescription Omega-3)

• Icosapent ethyl 2g twice daily is indicated as adjunct to maximally tolerated statin therapy for patients with triglycerides ≥150 mg/dL and established cardiovascular disease OR diabetes with ≥2 additional risk factors. 1, 3
• Provides 25% reduction in major adverse cardiovascular events (number needed to treat = 21). 1
• Monitor for increased risk of atrial fibrillation (3.1% hospitalization rate vs. 2.1% on placebo). 1
• Over-the-counter fish oil supplements are NOT equivalent to prescription formulations. 1

Renal Impairment

Initiate fenofibrate at 54 mg daily in patients with mild to moderately impaired renal function and increase only after evaluating effects on renal function and lipid levels; avoid fenofibrate in severe renal impairment. 4

Diabetes Management

Optimizing glycemic control in diabetic patients with severe hypertriglyceridemia is often more effective than additional lipid medications—poor glucose control is frequently the primary driver of severe hypertriglyceridemia. 1, 3

Monitoring Strategy

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications. 1, 2, 3
• Reassess lipids 4-8 weeks after initiating or adjusting pharmacotherapy. 1, 3
• Monitor liver function tests and creatine kinase if fenofibrate is added, particularly at baseline and 3 months after initiation. 1
• Once goals are achieved, follow-up every 6-12 months. 1

Common Pitfalls to Avoid

• Do NOT delay fibrate therapy while attempting lifestyle modifications alone in patients with triglycerides ≥500 mg/dL—pharmacologic intervention is mandatory to prevent pancreatitis. 1, 3
• Do NOT ignore secondary causes (uncontrolled diabetes, hypothyroidism, medications)—addressing these can dramatically reduce triglycerides without additional lipid medications. 1, 2, 3
• Do NOT use bile acid sequestrants when triglycerides are >200 mg/dL—they are relatively contraindicated. 1
• Do NOT substitute over-the-counter fish oil for prescription omega-3 fatty acids—they are not equivalent. 1
• Do NOT combine gemfibrozil with statins—use fenofibrate instead due to lower myopathy risk. 1, 3