What is the treatment for hypertriglyceridemia?

Treatment of Elevated 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), intensify lifestyle modifications and consider statins if LDL-C is elevated or cardiovascular risk is high; for mild hypertriglyceridemia (150-199 mg/dL), focus on lifestyle interventions and address secondary causes. 1, 2, 3

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

• Start fenofibrate 54-160 mg daily immediately as first-line therapy before addressing LDL cholesterol, as this provides 30-50% triglyceride reduction. 1, 4

• Implement extreme dietary fat restriction to <5% of total calories until triglycerides fall below 1,000 mg/dL, as medications have limited effectiveness above this threshold. 1

• Completely eliminate all added sugars and alcohol, as sugar directly increases hepatic triglyceride production and alcohol synergistically worsens hypertriglyceridemia and can precipitate pancreatitis. 1, 3

• Aggressively evaluate and treat secondary causes, particularly uncontrolled diabetes mellitus and hypothyroidism, as optimizing glucose control can dramatically reduce triglycerides independent of lipid medications. 1, 4

• Once triglycerides fall below 500 mg/dL, reassess LDL-C and initiate or optimize statin therapy if LDL-C is elevated or cardiovascular risk is high. 1

• Adjust fenofibrate dosing based on renal function: start at 54 mg daily in patients with mild to moderately impaired renal function, and avoid in severe renal impairment. 4

Moderate Hypertriglyceridemia (200-499 mg/dL)

• Continue or initiate statin therapy if LDL-C is elevated or 10-year ASCVD risk is ≥7.5%, as statins provide 10-30% dose-dependent triglyceride reduction plus proven cardiovascular benefit. 1, 2, 3

• Target non-HDL-C <130 mg/dL as a secondary goal when triglycerides are in this range. 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, 2

• Restrict added sugars to <6% of total daily calories and limit total fat to 30-35% of total daily calories. 1, 3

Mild Hypertriglyceridemia (150-199 mg/dL)

• Focus on lifestyle interventions as first-line therapy, including 5-10% weight loss (which reduces triglycerides by 20%), dietary modifications, and increased physical activity. 1, 2, 3

• Consider statin initiation if 10-year ASCVD risk is ≥7.5% or if persistently elevated nonfasting triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor. 1

Essential Lifestyle Interventions (All Severity Levels)

• Target 5-10% weight loss, which produces a 20% decrease in triglycerides and is the single most effective lifestyle intervention. 1, 2, 3

• Engage in ≥150 minutes/week of moderate-intensity aerobic activity (or 75 minutes/week vigorous activity), which reduces triglycerides by approximately 11%. 1, 3

• Limit or completely avoid alcohol consumption, as even 1 ounce daily increases triglycerides by 5-10%, and complete abstinence is mandatory for severe hypertriglyceridemia (≥500 mg/dL). 1, 3, 5

• Prioritize low-carbohydrate diets over low-fat diets, as they are more effective at lowering triglycerides. 1

Critical Secondary Causes to Address

• Optimize glycemic control in diabetic patients, as poor glucose control is often the primary driver of severe hypertriglyceridemia and can be more effective than additional medications. 1, 2, 4

• Screen for and treat hypothyroidism, as this is a common reversible cause of hypertriglyceridemia. 1, 5

• Review and discontinue or substitute medications that raise triglycerides, including thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, and antipsychotics. 1, 4

Combination Therapy 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, 2

• Monitor creatine kinase levels and muscle symptoms when using combination therapy, especially at baseline and 3 months after initiation. 1

• Fenofibrate has a better safety profile than gemfibrozil when combined with statins and should be preferred. 1

Monitoring Strategy

• Reassess fasting lipid panel in 4-8 weeks after initiating or adjusting fenofibrate therapy. 1

• Reassess in 6-12 weeks after implementing lifestyle modifications. 1, 2, 3

• 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. 4

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 overlook the importance of glycemic control in diabetic patients, as this can be more effective than additional medications in some cases. 1

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