What is the best approach to manage a patient with hypertriglyceridemia (elevated triglycerides)?

Management of Hypertriglyceridemia

Classification and Immediate Risk Assessment

The first step is to classify triglyceride severity, as this determines whether the primary goal is preventing pancreatitis (≥500 mg/dL) or reducing cardiovascular risk (<500 mg/dL). 1

Triglyceride levels are classified as:

• Normal: <150 mg/dL 1
• Mild: 150-199 mg/dL 1
• Moderate: 200-499 mg/dL 1
• Severe: 500-999 mg/dL (14% risk of pancreatitis) 1
• Very severe: ≥1,000 mg/dL (dramatic pancreatitis risk) 1

Evaluate and Address Secondary Causes FIRST

Before initiating any lipid-lowering therapy, aggressively evaluate for reversible causes 1:

• Uncontrolled diabetes: Check HbA1c immediately—poor glycemic control is often the primary driver of severe hypertriglyceridemia and optimizing glucose control can reduce triglycerides by 20-50% independent of medications 1, 2
• Alcohol consumption: Even 1 ounce daily raises triglycerides by 5-10%; complete abstinence is mandatory for levels ≥500 mg/dL 3, 1
• Hypothyroidism: Check TSH, as this is a common reversible cause 1
• Medications: Discontinue or substitute thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, and antipsychotics if possible 1
• Renal disease: Assess kidney function, as chronic kidney disease elevates triglycerides 1

Lifestyle Interventions (Foundation for ALL Patients)

Implement these interventions immediately alongside pharmacotherapy—do not delay treatment while attempting lifestyle changes alone for severe hypertriglyceridemia. 1

Weight Loss (Most Effective Single Intervention)

• Target 5-10% body weight reduction, which produces a 20% triglyceride decrease 3, 1
• In some patients, weight loss can reduce triglycerides by 50-70% 1

Dietary Modifications (Severity-Based)

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

• Restrict added sugars to <6% of total daily calories 3, 1
• Limit total fat to 30-35% of calories 1
• Restrict saturated fats to <7% of calories, replacing with polyunsaturated/monounsaturated fats 1
• Consume ≥2 servings/week of fatty fish (salmon, sardines, anchovies) 1

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

• Restrict total fat to 20-25% of calories 1
• Eliminate ALL added sugars completely 1
• Complete alcohol abstinence 1

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

• Implement extreme fat restriction to 10-15% of calories (or <5% until levels fall below 1,000 mg/dL) 1
• Eliminate all added sugars and alcohol 1

Physical Activity

• Engage in ≥150 minutes/week of moderate-intensity aerobic activity (or 75 minutes/week vigorous activity), which reduces triglycerides by approximately 11% 3, 1

Pharmacologic Therapy Algorithm

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

Initiate fenofibrate 54-160 mg daily IMMEDIATELY as first-line therapy to prevent acute pancreatitis, regardless of LDL-C levels or cardiovascular risk. 1, 4

• Fenofibrate reduces triglycerides by 30-50% 1, 4
• Start at 54 mg daily in patients with mild-moderate renal impairment (eGFR 30-59 mL/min/1.73 m²); do NOT exceed this dose 4
• Fenofibrate is contraindicated if eGFR <30 mL/min/1.73 m² 4
• Do NOT start with statin monotherapy at this level—statins provide only 10-30% triglyceride reduction, insufficient for pancreatitis prevention 1
• Once triglycerides fall below 500 mg/dL, reassess LDL-C and add statin therapy if LDL-C is elevated or cardiovascular risk is high 1

For Moderate Hypertriglyceridemia (200-499 mg/dL)

If 10-year ASCVD risk ≥7.5% OR LDL-C is elevated: 1

• Initiate moderate-to-high intensity statin therapy as first-line (e.g., atorvastatin 20-40 mg or rosuvastatin 10-20 mg daily) 1
• Statins provide 10-30% dose-dependent triglyceride reduction plus proven cardiovascular benefit 1
• Target LDL-C <100 mg/dL (or <70 mg/dL for very high-risk patients) and non-HDL-C <130 mg/dL 1

If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy: 1

• Add prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) if patient has established cardiovascular disease OR diabetes with ≥2 additional risk factors 1
• Icosapent ethyl demonstrated a 25% reduction in major adverse cardiovascular events (NNT=21) 1
• Alternatively, consider fenofibrate 54-160 mg daily if icosapent ethyl criteria are not met 1

For Mild Hypertriglyceridemia (150-199 mg/dL)

If 10-year ASCVD risk ≥7.5% and persistently elevated nonfasting triglycerides ≥175 mg/dL: 1

• Consider moderate-intensity statin therapy, as this constitutes a cardiovascular risk-enhancing factor 1

If ASCVD risk 5% to <7.5%: 1

• Engage in patient-clinician discussion regarding statin initiation 1

Combination Therapy Safety Considerations

When combining fenofibrate with statins (for patients requiring both triglyceride and LDL-C reduction): 1

• Use fenofibrate, NOT gemfibrozil—fenofibrate has a significantly better safety profile with lower myopathy risk 1
• Use lower statin doses to minimize myopathy risk, particularly in patients >65 years or with renal disease 1
• Monitor creatine kinase levels and muscle symptoms at baseline and follow-up 1
• Take fenofibrate in the morning and statins in the evening to minimize peak dose concentrations 1

Monitoring Strategy

• Recheck fasting lipid panel in 6-12 weeks after implementing lifestyle modifications 1
• Reassess lipids 4-8 weeks after initiating or adjusting pharmacotherapy 1
• Monitor liver function tests (AST/ALT) at baseline and every 3 months until normalization, then annually 1, 5
• Monitor renal function within 3 months after fenofibrate initiation and every 6 months thereafter; discontinue if eGFR persistently <30 mL/min/1.73 m² 1

Critical Pitfalls to Avoid

• Do NOT delay fibrate therapy for severe hypertriglyceridemia (≥500 mg/dL) while attempting lifestyle modifications alone—pharmacologic therapy is mandatory to prevent pancreatitis 1, 5
• Do NOT discontinue statins in favor of fibrate monotherapy in patients with cardiovascular risk or established disease—statins provide proven mortality benefit 1
• Do NOT use gemfibrozil when combining with statins—use fenofibrate instead due to lower myopathy risk 1
• Do NOT overlook uncontrolled diabetes as the primary driver—optimizing glycemic control may be more effective than additional lipid medications 1
• Do NOT use over-the-counter fish oil supplements as substitutes for prescription omega-3 formulations—they are not equivalent 1