What are the treatment options for an adult patient with hyperlipidemia and elevated triglycerides?

Treatment Options for Lowering Triglycerides

For adults with elevated triglycerides, the most effective interventions are weight loss (5-10% reduction produces 20% triglyceride decrease), complete elimination of added sugars and alcohol, fenofibrate for severe elevations ≥500 mg/dL, statins for moderate elevations with cardiovascular risk, and prescription omega-3 fatty acids (icosapent ethyl) as adjunctive therapy for patients with established cardiovascular disease or diabetes. 1

Lifestyle Interventions (First-Line for All Patients)

Weight Loss and Physical Activity

• Target 5-10% body weight reduction, which produces a 20% decrease in triglycerides—the single most effective lifestyle intervention 1
• In some patients, weight loss can reduce triglyceride levels by up to 50-70% 1
• Engage in ≥150 minutes/week of moderate-intensity aerobic activity (or 75 minutes/week vigorous activity), which reduces triglycerides by approximately 11% 1

Dietary Modifications

• For mild-moderate hypertriglyceridemia (150-499 mg/dL): Restrict added sugars to <6% of total daily calories and limit total fat to 30-35% of total calories 1
• For severe hypertriglyceridemia (500-999 mg/dL): Restrict dietary fat to 20-25% of total calories and eliminate added sugars completely 1
• For very severe hypertriglyceridemia (≥1,000 mg/dL): Implement a very low-fat diet (10-15% of total calories), and in some cases consider extreme dietary fat restriction (<5% of total calories) until triglycerides are ≤1,000 mg/dL 1
• Restrict saturated fats to <7% of total energy intake, replacing with monounsaturated or polyunsaturated fats 1
• Increase soluble fiber to >10 g/day 1
• Consume at least 2 servings per week of fatty fish rich in EPA and DHA 1

Alcohol Elimination

• Complete abstinence from alcohol is mandatory for patients with severe hypertriglyceridemia (≥500 mg/dL) to prevent hypertriglyceridemic pancreatitis 1
• Even 1 ounce of alcohol daily increases triglycerides by 5-10% 1

Pharmacologic Therapy (Algorithm Based on Triglyceride Level)

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

• Initiate fenofibrate 54-160 mg daily immediately as first-line therapy to prevent acute pancreatitis, before addressing LDL cholesterol 1, 2
• Fenofibrate reduces triglycerides by 30-50% 1, 3
• The initial dose for severe hypertriglyceridemia is 54 mg per day to 160 mg per day, with dosage individualized according to patient response at 4-8 week intervals 2
• For patients with mild to moderately impaired renal function, initiate fenofibrate at 54 mg per day and increase only after evaluation of effects on renal function and lipid levels 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

For Moderate Hypertriglyceridemia (200-499 mg/dL)

• If 10-year ASCVD risk is ≥7.5% or LDL-C is elevated, initiate moderate-to-high intensity statin therapy as first-line, which provides 10-30% dose-dependent triglyceride reduction plus proven cardiovascular benefit 1
• Target non-HDL-C <130 mg/dL 1
• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, consider adding prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) or fenofibrate 1

For Mild Hypertriglyceridemia (150-199 mg/dL)

• For patients with 10-year ASCVD risk ≥7.5%, consider initiating moderate-intensity statin therapy 1
• Persistently elevated nonfasting triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor 1

Prescription Omega-3 Fatty Acids (Adjunctive Therapy)

Icosapent Ethyl (Pure EPA)

• Indicated as adjunct to maximally tolerated statin therapy for patients with triglycerides ≥150 mg/dL who have either established cardiovascular disease OR diabetes with ≥2 additional risk factors 1
• Dose: 2g twice daily (total 4g/day) 1
• Provides 25% reduction in major adverse cardiovascular events (number needed to treat = 21) 1
• Monitor for increased risk of atrial fibrillation (3.1% hospitalization rate versus 2.1% on placebo) 1

Other Omega-3 Formulations

• Omega-3 carboxylic acid and omega-3-acid ethyl esters (EPA + DHA combinations) are FDA-approved only for severe hypertriglyceridemia (≥500 mg/dL) as adjunct to diet, not for cardiovascular risk reduction 1
• Prescription omega-3 fatty acids at 2-4g daily provide 20-50% triglyceride reduction when used as adjunctive therapy 1

Niacin (Limited Role)

• Niacin should generally not be used, as it showed no cardiovascular benefit when added to statin therapy, with increased risk of new-onset diabetes and gastrointestinal disturbances 1
• For patients with triglycerides ≥500 mg/dL, niacin can be considered as an alternative to fibrates before LDL-C reduction therapy, but fibrates are preferred due to better safety profile 1, 4
• Dose range: 500 mg to 2,000 mg once daily, initiated at 500 mg at bedtime with a low-fat snack 4

Addressing Secondary Causes

Optimize Glycemic Control

• In diabetic patients with severe hypertriglyceridemia, aggressively optimizing glycemic control can dramatically reduce triglycerides independent of lipid medications and may be more effective than additional medications 1, 3
• Poor glycemic control is often the primary driver of severe hypertriglyceridemia 1

Evaluate for Other Secondary Causes

• Check TSH to rule out hypothyroidism 1
• Assess for chronic kidney disease, nephrotic syndrome, and liver disease 1
• Review medications that raise triglycerides: thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, and antipsychotics 1

Combination Therapy Considerations

Statin Plus Fibrate

• When combining fenofibrate 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
• The ACCORD trial demonstrated no reduction in cardiovascular events with fenofibrate plus simvastatin compared to simvastatin alone 1

Critical Pitfalls to Avoid

• Do not delay fibrate therapy while attempting lifestyle modifications alone when triglycerides are ≥500 mg/dL—pharmacologic therapy is mandatory to prevent pancreatitis 1, 3
• 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
• Do not use over-the-counter fish oil as a substitute for prescription omega-3 fatty acids 3
• Do not combine gemfibrozil with statins due to significantly higher myopathy risk 1
• Do not ignore glycemic control in diabetic patients, as this is often more effective than additional lipid medications 1, 3

Monitoring Strategy

• Reassess fasting lipid panel in 4-8 weeks after initiating or adjusting therapy 1
• Monitor liver function tests and creatine kinase at baseline and during treatment with fibrates 1, 3
• Monitor renal function within 3 months after fenofibrate initiation and every 6 months thereafter 1
• Target goals: Triglycerides <200 mg/dL (ideally <150 mg/dL), non-HDL-C <130 mg/dL, and LDL-C <100 mg/dL for high-risk patients 1