What is the treatment for hypertriglyceridemia?

Treatment of Hypertriglyceridemia

Classification-Based Treatment Algorithm

The treatment of hypertriglyceridemia depends critically on the severity level: for severe hypertriglyceridemia (≥500 mg/dL), initiate fenofibrate 54-160 mg daily immediately to prevent acute pancreatitis; for moderate hypertriglyceridemia (200-499 mg/dL), prioritize lifestyle modifications and consider statins if LDL-C is elevated or cardiovascular risk is ≥7.5%; for mild hypertriglyceridemia (150-199 mg/dL), focus on lifestyle interventions and address secondary causes before considering pharmacotherapy. 1, 2, 3

Severity Classification

Hypertriglyceridemia is classified as follows: 1, 2, 3

• 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

Initial Assessment: Identify Secondary Causes

Before initiating any treatment, aggressively evaluate and address secondary causes, as correcting these may eliminate the need for pharmacotherapy: 1, 2, 3, 4

• Uncontrolled diabetes mellitus - Check HbA1c and fasting glucose; optimizing glycemic control can dramatically reduce triglycerides independent of lipid medications 1, 2
• Hypothyroidism - Check TSH 1, 3
• Excessive alcohol intake - Complete abstinence is mandatory for severe hypertriglyceridemia (≥500 mg/dL) 1, 3, 4
• Medications - Thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals should be discontinued or substituted if possible 1, 3, 4
• Chronic kidney disease or liver disease 1, 3
• Obesity and metabolic syndrome 1, 5

Lifestyle Modifications: First-Line for All Patients

Weight Loss

• Target a 5-10% body weight reduction, which produces a 20% decrease in triglycerides 1, 2, 3
• In some patients, weight loss can reduce triglyceride levels by up to 50-70% 1, 6

Dietary Modifications

For mild to moderate hypertriglyceridemia (150-499 mg/dL): 1, 2, 3

• Restrict added sugars to <6% of total daily calories 1, 3
• Limit total fat to 30-35% of total daily calories 1, 3
• Restrict saturated fats to <7% of total energy intake 1, 5
• Eliminate trans fatty acids completely 1

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

• Restrict total dietary fat to 20-25% of total daily calories 1, 3
• Eliminate all added sugars completely 1, 3

For very severe hypertriglyceridemia (≥1,000 mg/dL): 1, 3

• Implement a very low-fat diet (10-15% of total calories) 1, 3
• In some cases, consider extreme dietary fat restriction (<5% of total calories) until triglycerides fall below 1,000 mg/dL 1

Alcohol and Exercise

• Complete abstinence from alcohol for patients with severe hypertriglyceridemia (≥500 mg/dL); limit or avoid alcohol for all others 1, 2, 3, 4
• Engage in at least 150 minutes/week of moderate-intensity or 75 minutes/week of vigorous aerobic activity, which reduces triglycerides by approximately 11% 1, 2, 3

Omega-3 Fatty Acids from Diet

• Consume at least 2 servings per week of fatty fish (salmon, trout, sardines) rich in EPA and DHA 1

Pharmacologic Therapy Algorithm

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

Immediate pharmacologic intervention is mandatory to prevent acute pancreatitis: 1, 2, 3, 4

• Initiate fenofibrate 54-160 mg daily immediately as first-line therapy before addressing LDL cholesterol 1, 2, 4
• Fenofibrate reduces triglycerides by 30-50% 1, 2, 7
• The initial dose for severe hypertriglyceridemia is 54-160 mg per day, individualized according to patient response 4
• Dosage should be adjusted if necessary following repeat lipid determinations at 4-8 week intervals 4
• For patients with mild to moderately impaired renal function, initiate at 54 mg per day and increase only after evaluation of effects on renal function and lipid levels 4
• Fenofibrate is contraindicated in patients with severe renal impairment, active liver disease, or preexisting gallbladder disease 4

Once triglycerides fall below 500 mg/dL: 1, 2

• Reassess LDL-C and consider adding statin therapy if LDL-C is elevated or cardiovascular risk is high 1, 2

If triglycerides remain elevated after fenofibrate and lifestyle optimization: 1, 2

• Add prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) as adjunctive therapy 1, 2

Moderate Hypertriglyceridemia (200-499 mg/dL)

For patients with elevated LDL-C or 10-year ASCVD risk ≥7.5%: 1, 2

• Initiate moderate-to-high intensity statin therapy (atorvastatin 10-40 mg or rosuvastatin 5-20 mg daily) as first-line pharmacologic therapy 1
• Statins provide 10-30% dose-dependent triglyceride reduction and proven cardiovascular benefit 1, 2, 7
• Target non-HDL-C <130 mg/dL (calculated as total cholesterol minus HDL-C) 1, 2

If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy: 1, 2

• Consider adding 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
• Icosapent ethyl demonstrated a 25% reduction in major adverse cardiovascular events (number needed to treat = 21) 1
• Alternatively, consider fenofibrate 54-160 mg daily if icosapent ethyl criteria are not met 1, 2

Mild Hypertriglyceridemia (150-199 mg/dL)

For patients with 10-year ASCVD risk ≥7.5%: 1

• Consider initiating moderate-intensity statin therapy if persistently elevated nonfasting triglycerides ≥175 mg/dL, as this constitutes a cardiovascular risk-enhancing factor 1

For patients with ASCVD risk 5% to <7.5%: 1

• Engage in patient-clinician discussion regarding statin initiation 1

For all patients with mild hypertriglyceridemia: 1, 2, 3

• Prioritize aggressive lifestyle modifications before considering pharmacotherapy 1, 2, 3

Combination Therapy Safety Considerations

When combining fenofibrate with statins: 1, 2

• Use lower statin doses to minimize myopathy risk, particularly in patients >65 years or with renal disease 1, 2
• Fenofibrate has a better safety profile than gemfibrozil when combined with statins 1, 7
• Monitor creatine kinase levels and muscle symptoms, especially at baseline and 3 months after initiation 1, 2
• The combination of high-dose statin plus fibrate significantly increases myopathy risk 1, 2

Monitoring and Follow-Up

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications 1, 2, 3
• Reassess lipids 4-8 weeks after initiating or adjusting pharmacotherapy 1, 2
• 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
• Monitor for increased risk of atrial fibrillation with prescription omega-3 fatty acids 1

Critical 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, 2
• Do not start with statin monotherapy when triglycerides are ≥500 mg/dL - statins provide only 10-30% triglyceride reduction and are insufficient for preventing pancreatitis at this level 1, 2
• Do not use gemfibrozil when combining with statins - fenofibrate has a significantly better safety profile 1, 7
• Do not ignore secondary causes - uncontrolled diabetes, hypothyroidism, or certain medications can lead to unnecessary medication treatment 1, 2, 3
• Do not use over-the-counter fish oil supplements as a substitute for prescription omega-3 formulations - they are not equivalent 1