What is the treatment for high triglycerides (hypertriglyceridemia)?

Treatment of High Triglycerides (Hypertriglyceridemia)

Treatment is stratified by triglyceride level severity, with lifestyle modifications forming the foundation for all patients, while pharmacologic therapy is mandatory for severe elevations (≥500 mg/dL) to prevent pancreatitis, and should be considered for moderate elevations (200-499 mg/dL) based on cardiovascular risk. 1

Classification and Risk Assessment

Triglyceride levels are classified as: 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 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 Addressing these underlying causes may eliminate the need for specific triglyceride-lowering therapy. 4

Lifestyle Interventions (All Patients)

Weight loss is the most effective lifestyle intervention, with 5-10% body weight reduction associated with a 20% decrease in triglycerides, and in some patients up to 50-70% reduction. 1, 2

Dietary Modifications by Severity:

For mild to moderate hypertriglyceridemia (150-499 mg/dL): 1, 3

• Restrict added sugars to <6% of total daily calories
• Limit total fat to 30-35% of total daily calories
• Low-carbohydrate diets are more effective than low-fat diets 1

For severe hypertriglyceridemia (500-999 mg/dL): 1, 3

• 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, 3

• Eliminate added sugars completely
• Restrict total fat to 10-15% of daily calories
• In some cases, consider extreme dietary fat restriction (<5% of total calories) until triglycerides drop below 1,000 mg/dL 1

Physical Activity and Alcohol:

• Engage in at least 150 minutes/week of moderate-intensity or 75 minutes/week of vigorous aerobic activity 1, 2
• Limit or completely avoid alcohol consumption, especially with severe hypertriglyceridemia, as alcohol significantly raises triglyceride levels 1, 2, 3

Pharmacologic Therapy Algorithm

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

Fibrates are first-line therapy and must be initiated immediately to prevent acute pancreatitis, regardless of cardiovascular risk. 1, 2, 4

• Start fenofibrate 54-200 mg daily immediately before addressing LDL cholesterol 1, 4
• Dosage should be individualized according to patient response with repeat lipid determinations at 4-8 week intervals 4
• Maximum dose is 160 mg once daily 4
• Critical pitfall: 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

Special consideration for diabetic patients: Poor glycemic control is often the primary driver of severe hypertriglyceridemia. Optimizing diabetes management can dramatically reduce triglycerides independent of lipid-lowering medications and may obviate the need for pharmacologic intervention. 1, 4

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

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

Statins are first-line pharmacologic therapy if there is elevated LDL-C or increased cardiovascular risk (10-year ASCVD risk ≥7.5%). 1, 2

• Statins provide a 10-30% dose-dependent reduction in triglycerides 1, 2
• If triglycerides remain elevated >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, consider adding prescription omega-3 fatty acids (icosapent ethyl 2-4 g/day) 1
• Alternatively, fibrates (fenofibrate 54-160 mg daily) can be considered after addressing secondary causes 1

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

For patients with 10-year ASCVD risk 7.5% to <20% and persistently elevated nonfasting triglycerides ≥175 mg/dL, consider statin initiation. 1

Adjunctive Therapy: Prescription Omega-3 Fatty Acids

Prescription omega-3 fatty acids (2-4 g/day) can be added as adjunctive therapy for patients with persistent hypertriglyceridemia despite lifestyle modifications and primary pharmacologic therapy. 1, 2, 3

• Icosapent ethyl (prescription EPA) is indicated as an adjunct to maximally tolerated statin therapy to reduce cardiovascular risk in patients with triglycerides ≥150 mg/dL and established cardiovascular disease or diabetes with ≥2 additional risk factors 1
• Monitor for increased risk of atrial fibrillation with prescription omega-3 fatty acids 1
• Over-the-counter fish oil supplements are not equivalent to prescription formulations and should not be substituted 1

Combination Therapy Considerations

When combining fibrates with statins: 1, 2

• The combination increases myopathy risk
• Statin doses should be kept relatively low with this combination
• Monitor for muscle symptoms and obtain baseline and follow-up CPK levels
• Fenofibrate has a better safety profile than gemfibrozil when combined with statins

Avoid bile acid sequestrants when triglycerides are >200 mg/dL, as they are relatively contraindicated. 1

Monitoring and Follow-up

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications or starting pharmacotherapy 1, 2
• For patients on fenofibrate, repeat lipid determinations at 4-8 week intervals 4
• Therapy should be withdrawn in patients who do not have an adequate response after two months of treatment with the maximum recommended dose of 160 mg once daily 4
• Consider reducing the dosage of fenofibrate if lipid levels fall significantly below the targeted range 4

Special Populations

Patients with impaired renal function: 4

• Initiate fenofibrate at 54 mg per day in patients with mild to moderately impaired renal function
• Increase dose only after evaluation of effects on renal function and lipid levels
• Avoid fenofibrate in patients with severe renal impairment

Geriatric patients: Dose selection should be made on the basis of renal function. 4

Common Pitfalls to Avoid

• Do not delay fibrate initiation while attempting lifestyle modifications alone in patients with triglyceride levels ≥500 mg/dL, as pharmacologic therapy is mandatory 1
• Do not overlook the importance of glycemic control in diabetic patients, as this can be more effective than additional medications in some cases 1
• Do not reduce current doses of fenofibrate or statins in patients with severe hypertriglyceridemia who need maximum lipid-lowering therapy 1
• Do not delay aggressive dietary intervention while waiting for medications to take effect 1