What are the treatment options for hypertriglyceridemia (high triglycerides)?

Treatment of Hypertriglyceridemia

Classification-Based Treatment Algorithm

The treatment of high triglycerides depends critically on the severity level: for mild-moderate hypertriglyceridemia (150-499 mg/dL), prioritize lifestyle modifications and statins if cardiovascular risk is ≥7.5%; for severe hypertriglyceridemia (≥500 mg/dL), immediately initiate fenofibrate to prevent acute pancreatitis regardless of cardiovascular risk. 1

Mild Hypertriglyceridemia (150-199 mg/dL)

• Lifestyle modifications are first-line therapy, targeting 5-10% weight loss which produces approximately 20% triglyceride reduction 1
• Restrict added sugars to <6% of total daily calories, as sugar intake directly increases hepatic triglyceride production 1
• Limit total dietary fat to 30-35% of total calories, with saturated fats <7% 1
• Engage in at least 150 minutes per week of moderate-intensity aerobic activity, which reduces triglycerides by approximately 11% 1
• Complete alcohol abstinence or severe restriction, as even 1 ounce daily increases triglycerides by 5-10% 1
• Statins should be considered if 10-year ASCVD risk is ≥7.5%, providing 10-30% dose-dependent triglyceride reduction plus proven cardiovascular benefit 1

Moderate Hypertriglyceridemia (200-499 mg/dL)

• Continue aggressive lifestyle modifications as outlined above 1
• Statins are first-line pharmacologic therapy if 10-year ASCVD risk ≥7.5%, addressing both LDL-C and triglycerides 1, 2
• Target non-HDL-C <130 mg/dL as a secondary goal 1
• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, add prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) for patients with established cardiovascular disease OR diabetes with ≥2 additional risk factors 1
• Icosapent ethyl demonstrated 25% reduction in major adverse cardiovascular events (number needed to treat = 21) 1
• Monitor for increased risk of atrial fibrillation with prescription omega-3 fatty acids 1

Severe Hypertriglyceridemia (500-999 mg/dL)

This level carries 14% risk of acute pancreatitis and requires immediate pharmacologic intervention. 1

• Initiate fenofibrate 54-160 mg daily immediately as first-line therapy to prevent pancreatitis, before addressing LDL cholesterol 1, 3
• Fenofibrate reduces triglycerides by 30-50% 1
• Restrict total dietary fat to 20-25% of total daily calories 1, 2
• Eliminate all added sugars completely 1
• Complete alcohol abstinence is mandatory, as alcohol can precipitate hypertriglyceridemic pancreatitis at this level 1
• Aggressively evaluate and treat secondary causes, particularly uncontrolled diabetes and hypothyroidism, as optimizing glucose control can dramatically reduce triglycerides independent of lipid medications 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
• Consider adding prescription omega-3 fatty acids (2-4g daily) as adjunctive therapy if triglycerides remain elevated 1

Very Severe Hypertriglyceridemia (≥1000 mg/dL)

• Implement extreme dietary fat restriction (<5-15% of total calories) until triglycerides fall below 1000 mg/dL 1, 2
• Initiate fenofibrate 54-160 mg daily immediately 1, 3
• Completely eliminate all added sugars and alcohol 1
• Assess for and aggressively treat underlying secondary causes, particularly diabetes with poor glycemic control 1
• Add prescription omega-3 fatty acids (2-4g/day) as adjunctive therapy 1
• Monitor for myositis risk if combining fenofibrate with statins, particularly checking creatine kinase levels 1

Critical Secondary Causes to Address

Before or concurrent with pharmacologic therapy, evaluate and treat: 1, 3

• Uncontrolled diabetes mellitus (often the primary driver of severe hypertriglyceridemia)
• Hypothyroidism
• Chronic kidney disease
• Excessive alcohol consumption
• Medications that raise triglycerides: thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, antipsychotics

Combination Therapy Safety Considerations

• 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
• Fenofibrate is preferred over gemfibrozil when combining with statins, as fenofibrate has a better safety profile with lower myopathy risk 1
• Monitor creatine kinase levels and muscle symptoms when using combination therapy 1

Dosing Considerations

• For severe hypertriglyceridemia, fenofibrate dosing is 54-160 mg daily, individualized according to patient response with repeat lipid determinations at 4-8 week intervals 3
• In patients with mild-moderate renal impairment, initiate fenofibrate at 54 mg daily and increase only after evaluating effects on renal function 3
• Fenofibrate should be avoided in severe renal impairment 3
• Fenofibrate should be given with meals to optimize bioavailability 3

Common Pitfalls to Avoid

• Do not delay fibrate therapy while attempting lifestyle modifications alone when triglycerides are ≥500 mg/dL—pharmacologic therapy is mandatory to prevent pancreatitis 1
• Do not start with statin monotherapy when triglycerides are ≥500 mg/dL, as statins provide only 10-30% triglyceride reduction and are insufficient for preventing pancreatitis 1
• Do not use gemfibrozil instead of fenofibrate—gemfibrozil has significantly higher myopathy risk when combined with statins 1
• Do not use over-the-counter fish oil supplements as substitutes for prescription omega-3 formulations, as they are not equivalent 1
• Therapy should be withdrawn if no adequate response after 2 months of maximum dose (160 mg daily) 3

Monitoring Strategy

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications 1
• Monitor lipid levels at 4-8 week intervals after initiating or adjusting fenofibrate 1, 3
• Once goals are achieved, follow-up every 6-12 months 1