What is the treatment for elevated triglycerides (hypertriglyceridemia)?

Treatment of Elevated Triglycerides

The treatment approach for hypertriglyceridemia depends critically on the severity of elevation: for triglycerides ≥500 mg/dL, initiate fenofibrate immediately to prevent acute pancreatitis; for moderate elevation (200-499 mg/dL), prioritize lifestyle modifications and statin therapy if cardiovascular risk is elevated; for mild elevation (150-199 mg/dL), focus on lifestyle changes with consideration of statins based on 10-year ASCVD risk. 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 at this level. 1

• Start fenofibrate 54-160 mg daily immediately as first-line therapy, before addressing LDL cholesterol—this is non-negotiable at triglyceride levels ≥500 mg/dL. 1, 2
• Fenofibrate reduces triglycerides by 30-50% and should be given with meals to optimize bioavailability. 1, 2
• 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

Critical dietary interventions must be implemented simultaneously:

• Restrict total dietary fat to 20-25% of total calories for triglycerides 500-999 mg/dL, or 10-15% for levels ≥1,000 mg/dL. 1, 3
• Eliminate all added sugars completely, as sugar intake directly increases hepatic triglyceride production. 1
• Abstain completely from all alcohol consumption—even 1 ounce daily increases triglycerides by 5-10%, and alcohol can precipitate hypertriglyceridemic pancreatitis. 1

Urgent assessment for secondary causes:

• Check hemoglobin A1c and fasting glucose immediately, as uncontrolled diabetes is often the primary driver of severe hypertriglyceridemia. 1
• Optimize glycemic control aggressively—this can dramatically reduce triglycerides independent of lipid medications. 1
• Evaluate for hypothyroidism, renal disease, and medications that raise triglycerides (thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals). 1, 2

Once triglycerides fall below 500 mg/dL:

• Reassess LDL-C and consider adding statin therapy if LDL-C is elevated or cardiovascular risk is high. 1
• Add prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) if triglycerides remain >200 mg/dL after 3 months of fenofibrate plus optimized lifestyle. 1

Moderate Hypertriglyceridemia (200-499 mg/dL)

Statins are first-line pharmacologic therapy if 10-year ASCVD risk is ≥7.5% or if LDL-C is elevated. 1, 3

• Initiate moderate-to-high intensity statin therapy (atorvastatin 10-40 mg or rosuvastatin 5-20 mg daily), which provides 10-30% dose-dependent triglyceride reduction plus proven cardiovascular benefit. 1
• Target non-HDL-C <130 mg/dL (calculated as total cholesterol minus HDL-C). 1

Lifestyle modifications are essential:

• Target 5-10% weight loss, which produces a 20% decrease in triglycerides—this is the single most effective lifestyle intervention. 1
• Restrict added sugars to <6% of total daily calories. 1, 3
• Limit total fat to 30-35% of total daily calories, restricting saturated fats to <7% and replacing with monounsaturated or polyunsaturated fats. 1
• Engage in at least 150 minutes per week of moderate-intensity aerobic activity, which reduces triglycerides by approximately 11%. 1
• Limit or completely 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 daily) for patients with established cardiovascular disease OR diabetes with ≥2 additional risk factors—this provides a 25% reduction in major adverse cardiovascular events. 1, 4
• Alternatively, consider fenofibrate 54-160 mg daily if icosapent ethyl criteria are not met, though combination statin-fibrate therapy increases myopathy risk. 1

Mild Hypertriglyceridemia (150-199 mg/dL)

Lifestyle modifications are the primary intervention. 1

• Implement the same dietary and exercise recommendations as for moderate hypertriglyceridemia. 1
• For adults 40-75 years with persistently elevated nonfasting triglycerides ≥175 mg/dL and 10-year ASCVD risk ≥7.5%, consider statin initiation. 1
• If ASCVD risk is 5% to <7.5%, engage in patient-clinician discussion regarding statin initiation, as persistently elevated triglycerides constitute a cardiovascular risk-enhancing factor. 1

Critical 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
• Use fenofibrate rather than gemfibrozil when combining with statins—gemfibrozil has significantly higher myopathy risk and should be avoided. 1
• Monitor creatine kinase levels and muscle symptoms at baseline and during therapy. 1

For patients with renal impairment:

• Initiate fenofibrate at 54 mg daily in patients with mild to moderately impaired renal function and increase only after evaluating effects on renal function and lipid levels. 2
• Avoid fenofibrate in patients with severe renal impairment. 2

With prescription omega-3 fatty acids:

• Monitor for increased risk of atrial fibrillation (3.1% hospitalization rate versus 2.1% on placebo). 1
• Over-the-counter fish oil supplements are not equivalent to prescription formulations and should not be substituted. 1

Common Pitfalls to Avoid

• Do not delay fibrate initiation while attempting lifestyle modifications alone in patients with triglycerides ≥500 mg/dL—pharmacologic therapy is mandatory to prevent pancreatitis. 1
• Do not overlook secondary causes, particularly uncontrolled diabetes and hypothyroidism, which may obviate the need for additional lipid medications when properly treated. 1, 2
• Do not use niacin routinely—it showed no cardiovascular benefit when added to statin therapy and increases risk of new-onset diabetes. 1
• Do not reduce statin doses in patients with well-controlled LDL-C when adding triglyceride-lowering therapy, unless combining with fibrates. 1

Monitoring Strategy

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications. 1
• Evaluate lipids 4-8 weeks after initiating or adjusting pharmacotherapy. 1, 2
• Once goals are achieved, follow up every 6-12 months. 1
• Consider reducing fenofibrate dosage if lipid levels fall significantly below the targeted range. 2
• Withdraw therapy in patients who do not have an adequate response after two months of treatment with the maximum recommended dose of 160 mg once daily. 2