What is the treatment for hypertriglyceridemia?

Treatment for High Triglycerides

The treatment approach for hypertriglyceridemia depends critically on the triglyceride level: for levels ≥500 mg/dL, initiate fibrates immediately to prevent pancreatitis; for levels 200-499 mg/dL, start with statins if cardiovascular risk is elevated (10-year ASCVD risk ≥7.5%); and for all levels, implement aggressive lifestyle modifications including dietary fat restriction and elimination of alcohol and added sugars. 1, 2, 3

Classification-Based Treatment Algorithm

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

Immediate pharmacologic intervention is mandatory to prevent acute pancreatitis, regardless of cardiovascular risk 1, 2, 3:

• Start fenofibrate 54-200 mg daily immediately as first-line therapy before addressing LDL cholesterol 1, 4
• Implement extreme dietary fat restriction to <5% of total calories until triglycerides fall below 1,000 mg/dL, as pharmacotherapy has limited effectiveness above this threshold 1, 3
• Completely eliminate added sugars and all alcohol consumption 1, 2, 3
• Aggressively treat secondary causes, particularly uncontrolled diabetes, as optimizing glycemic control can dramatically reduce triglycerides independent of lipid medications 1, 3

Critical pitfall to avoid: 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 at this level 1, 3

Once triglycerides are reduced below 500 mg/dL with fibrate therapy, then initiate or optimize statin therapy to address LDL-C and cardiovascular risk 1, 3

Moderate Hypertriglyceridemia (200-499 mg/dL)

Statins are first-line pharmacologic therapy if 10-year ASCVD risk is ≥7.5% 1, 2, 3:

• Initiate at least moderate-intensity statin therapy, which provides 10-30% dose-dependent triglyceride reduction 1, 3
• Target non-HDL cholesterol <130 mg/dL (calculated as total cholesterol minus HDL cholesterol) 2, 3, 5
• Restrict dietary fat to 20-25% of total daily calories 2, 3
• Limit added sugars to <6% of total daily calories 2, 3

If triglycerides remain elevated >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, 3

For patients with 10-year ASCVD risk 5% to <7.5%, engage in patient-clinician discussion regarding statin initiation 1

Mild Hypertriglyceridemia (150-199 mg/dL)

Persistently elevated nonfasting triglycerides ≥175 mg/dL is a risk-enhancing factor that supports statin initiation in primary prevention patients with 10-year ASCVD risk 7.5% to <20% 1, 3

• Prioritize lifestyle modifications: target 5-10% weight loss, which can reduce triglycerides by 20% 2, 3
• Engage in at least 150 minutes per week of moderate-intensity aerobic activity 2, 3, 6
• Limit alcohol to maximum 1 drink/day for women, 2 drinks/day for men 6

Essential Lifestyle Modifications (All Levels)

Weight loss is the most effective lifestyle intervention, with 5-10% body weight reduction associated with 20% decrease in triglycerides; some patients achieve up to 50-70% reduction 2, 3, 7:

• Low-carbohydrate diets are more effective than low-fat diets for triglyceride reduction in many patients 2, 3
• Emphasize vegetables, legumes, and lean proteins while limiting fruit to 3-4 servings per day 6
• Completely eliminate or severely restrict alcohol, as it significantly raises triglyceride levels 1, 2, 3, 4
• Address excess body weight and increase physical exercise as ancillary measures 4

Secondary Causes to Address First

Identify and treat contributory conditions before or concurrent with pharmacotherapy 1, 3, 4:

• Optimize glycemic control in diabetic patients, particularly those with very high triglycerides and poor control—this may obviate the need for additional lipid medications 1, 3, 4
• Evaluate and treat hypothyroidism 3, 4, 8
• Review medications: estrogen therapy, thiazide diuretics, and beta-blockers can cause massive triglyceride elevations, especially in familial hypertriglyceridemia 4
• Discontinuation of the causative agent may eliminate the need for specific triglyceride therapy 4

Adjunctive Pharmacotherapy

Prescription omega-3 fatty acids (icosapent ethyl 2-4 g/day) can be added if triglycerides remain persistently elevated after statin or fibrate therapy 1, 2, 3:

• Specifically indicated for patients with established cardiovascular disease or diabetes with ≥2 additional risk factors on statin therapy with triglycerides 150-499 mg/dL 3
• Monitor for increased risk of atrial fibrillation with prescription omega-3 fatty acids 3
• Over-the-counter fish oil supplements are not equivalent to prescription formulations and should not be substituted 3

Combination Therapy Considerations

When combining fibrates with statins, use caution due to increased myositis risk 2, 3:

• Fenofibrate has a better safety profile than gemfibrozil when combined with statins 3
• Keep statin doses relatively low when using combination therapy 3
• Monitor for muscle symptoms and obtain baseline and follow-up creatine kinase levels 3
• Avoid bile acid sequestrants when triglycerides are >200 mg/dL, as they are relatively contraindicated 3

Monitoring and Follow-Up

Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications 3, 6:

• For severe hypertriglyceridemia on fibrate therapy, repeat lipid determinations at 4-8 week intervals 4
• Withdraw therapy in patients who do not have adequate response after 2 months of treatment with maximum recommended dose 4
• Consider reducing fenofibrate dosage if lipid levels fall significantly below targeted range 4

Special Populations

For patients with renal impairment, initiate fenofibrate at 54 mg/day and increase only after evaluating effects on renal function and lipid levels 4:

• Avoid fenofibrate in severe renal impairment including dialysis patients 4
• Dose selection for elderly patients should be based on renal function 4