What is the treatment for hypertriglyceridemia?

Treatment for High Triglycerides

The treatment approach for hypertriglyceridemia depends critically on the triglyceride level: for severe hypertriglyceridemia (≥500 mg/dL), immediately initiate fenofibrate 54-160 mg daily to prevent acute pancreatitis; for moderate hypertriglyceridemia (200-499 mg/dL), start with intensive lifestyle modifications and statin therapy if cardiovascular risk is ≥7.5%; for mild hypertriglyceridemia (150-199 mg/dL), focus on lifestyle interventions and address secondary causes before considering pharmacotherapy. 1

Classification-Based Treatment Algorithm

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

Immediate pharmacologic intervention is mandatory to prevent acute pancreatitis, which occurs in 14% of patients with severe hypertriglyceridemia. 1

First-line therapy:

• Initiate fenofibrate 54-160 mg daily immediately, before addressing LDL cholesterol. 1, 2
• Fenofibrate reduces triglycerides by 30-50%. 1
• Dosing should be individualized based on response, with repeat lipid measurements at 4-8 week intervals. 2

Critical dietary interventions (implement simultaneously):

• Restrict total dietary fat to 20-25% of total daily calories for triglycerides 500-999 mg/dL. 1
• For very severe hypertriglyceridemia (≥1000 mg/dL), implement extreme fat restriction to 10-15% of total calories. 1, 3
• Eliminate all added sugars completely, as sugar intake directly increases hepatic triglyceride production. 1
• Abstain completely from all alcohol consumption, as alcohol can precipitate hypertriglyceridemic pancreatitis at these levels. 1, 2

Address secondary causes 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
• Evaluate and treat hypothyroidism, renal disease, and liver disease. 1
• Discontinue or substitute medications that raise triglycerides (thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, antipsychotics). 1, 2

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 (icosapent ethyl 2-4g/day) if triglycerides remain persistently elevated. 1

Moderate Hypertriglyceridemia (200-499 mg/dL)

For patients with 10-year ASCVD risk ≥7.5%:

• Initiate statin therapy as first-line pharmacologic treatment, which provides 10-30% triglyceride reduction while addressing cardiovascular risk. 1, 3
• Target non-HDL-C <130 mg/dL. 1

Lifestyle modifications (implement for 3 months before escalating therapy):

• Target 5-10% body weight reduction, which produces a 20% decrease in triglycerides. 1
• Restrict total fat to 30-35% of total daily calories. 1
• Limit added sugars to <6% of total daily calories. 1
• Engage in at least 150 minutes per week of moderate-intensity aerobic activity. 1, 3
• Limit or avoid alcohol consumption. 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/day) as adjunctive therapy. 1
• Icosapent ethyl 2g twice daily reduces major adverse cardiovascular events by 25% in patients with 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

Alternative option:

• Consider fenofibrate as add-on therapy if triglycerides remain significantly elevated and cardiovascular risk is high. 1

Mild Hypertriglyceridemia (150-199 mg/dL)

Primary approach is lifestyle modification:

• Weight loss of 5-10% can reduce triglycerides by 20%, and in some patients by up to 50-70%. 1
• Low-carbohydrate diets are more effective at lowering triglycerides than low-fat diets. 1
• Consume ≥2 servings (8+ ounces) per week of fatty fish (salmon, trout, sardines, anchovies). 1
• Engage in ≥150 minutes/week of moderate-intensity aerobic activity, which reduces triglycerides by approximately 11%. 1

For patients with 10-year ASCVD risk 7.5% to <20% and persistently elevated nonfasting triglycerides ≥175 mg/dL:

• Consider statin initiation, as persistently elevated triglycerides are a risk-enhancing factor for cardiovascular disease. 1

Critical Safety Considerations

When combining fibrates with statins:

• Use lower statin doses to minimize myopathy risk, particularly in patients >65 years or with renal disease. 1
• Fenofibrate has a better safety profile than gemfibrozil when combined with statins. 1
• Monitor creatine kinase levels and muscle symptoms. 1
• Avoid fibrate-statin combinations when possible due to increased myositis risk. 3

Renal function considerations:

• Initiate fenofibrate at 54 mg daily in patients with mild to moderately impaired renal function. 2
• Avoid fenofibrate in patients with severe renal impairment, including those receiving dialysis. 2
• Base fenofibrate dose selection on renal function in elderly patients. 1

Contraindications to fenofibrate:

• Active liver disease, including primary biliary cirrhosis and unexplained persistent liver function abnormalities. 2
• Preexisting gallbladder disease. 2
• Known hypersensitivity to fenofibrate or fenofibric acid. 2

Common Pitfalls 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

Do not delay fibrate initiation while attempting lifestyle modifications alone in patients with triglycerides ≥500 mg/dL, as pharmacologic therapy is mandatory. 1

Do not use over-the-counter fish oil supplements as substitutes for prescription omega-3 formulations, as they are not equivalent. 1

Do not use bile acid sequestrants when triglycerides are >200 mg/dL, as they are relatively contraindicated. 1

Do not overlook secondary causes, particularly uncontrolled diabetes, hypothyroidism, and medications that raise triglycerides, as addressing these may obviate the need for additional lipid medications. 1, 2

Monitoring Strategy

For severe hypertriglyceridemia:

• Reassess lipid levels at 4-8 week intervals after initiating or adjusting fenofibrate. 1, 2
• Withdraw therapy if no adequate response after 2 months of treatment with maximum recommended dose of 160 mg daily. 2

For moderate hypertriglyceridemia:

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications. 1
• Once goals are achieved, follow-up every 6-12 months. 1