What is the treatment for hypertriglyceridemia?

Treatment of High Triglycerides

Treatment of hypertriglyceridemia must be stratified by severity, with lifestyle modifications forming the foundation for all levels, fibrates as first-line pharmacologic therapy for severe/very severe levels (≥500 mg/dL) to prevent pancreatitis, and statins for moderate levels when cardiovascular risk or elevated LDL-C is present. 1, 2

Initial Assessment

Before initiating treatment, evaluate for secondary causes that may be driving triglyceride elevation: 1, 2

• Excessive alcohol intake - must be addressed or eliminated entirely 1
• Uncontrolled diabetes mellitus - optimize glycemic control first, as this alone can dramatically reduce triglycerides 1, 3
• Hypothyroidism - check TSH and treat if abnormal 1
• Renal disease - assess kidney function 1
• Medications - review for thiazides, beta-blockers, estrogen, corticosteroids 1

Classification-Based Treatment Algorithm

Normal to Mild (< 200 mg/dL)

• Focus on lifestyle modifications and cardiovascular risk assessment 1
• Consider statin therapy if 10-year ASCVD risk ≥7.5% 3

Moderate Hypertriglyceridemia (200-499 mg/dL)

Lifestyle interventions: 1, 2

• Target 5-10% weight loss (can reduce triglycerides by up to 20%) 1
• Restrict added sugars to <6% of total daily calories 1
• Limit total fat to 30-35% of total daily calories 1
• Engage in at least 150 minutes/week of moderate-intensity aerobic activity 1
• Limit or avoid alcohol consumption 1

Pharmacologic approach: 2, 3

• Statins are first-line if elevated LDL-C or increased cardiovascular risk exists (provide 10-30% triglyceride reduction) 2
• Target non-HDL-C <130 mg/dL 3
• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, add prescription omega-3 fatty acids (icosapent ethyl 2-4 g/day) 3

Severe Hypertriglyceridemia (500-999 mg/dL)

This level requires immediate pharmacologic intervention to prevent pancreatitis. 1, 2

Dietary modifications: 1

• Further restrict added sugars to <5% of total daily calories 1
• Restrict total fat to 20-25% of total daily calories 1
• Completely eliminate alcohol 1

Pharmacologic approach: 1, 2

• Fibrates are first-line therapy - start fenofibrate 54-200 mg daily immediately 1, 4
• Do not start with statin monotherapy at this level, as statins provide only 10-30% triglyceride reduction and are insufficient for preventing pancreatitis 3
• Once triglycerides are reduced below 500 mg/dL with fibrate therapy, then initiate or optimize statin therapy to address LDL-C and cardiovascular risk 3

Very Severe Hypertriglyceridemia (≥1,000 mg/dL)

This is a medical urgency requiring aggressive intervention to prevent acute pancreatitis. 1

Dietary modifications: 1

• Eliminate added sugars completely 1
• Restrict total fat to 10-15% of daily calories 1
• In some cases, consider extreme dietary fat restriction (<5% of total calories) until triglycerides are <1,000 mg/dL 3
• Absolute alcohol abstinence 1

Pharmacologic approach: 1, 3

• Immediate fibrate therapy is mandatory - fenofibrate 200 mg daily 4
• Aggressively optimize glycemic control in diabetic patients, as poor control is often the primary driver 3
• Consider adding prescription omega-3 fatty acids (2-4 g/day) as adjunctive therapy 1, 3

Specific Pharmacologic Agents

Fibrates (First-line for severe/very severe hypertriglyceridemia)

• Fenofibrate dosing: 54-160 mg daily for severe hypertriglyceridemia; individualize based on response 4
• Can reduce triglycerides by 30-50% 3
• Must be given with meals to optimize bioavailability 4
• Monitor lipid levels at 4-8 week intervals after initiation 3
• Contraindicated in severe renal impairment, active liver disease, preexisting gallbladder disease 4

Statins (First-line for moderate hypertriglyceridemia with cardiovascular risk)

• Provide 10-30% dose-dependent triglyceride reduction 3
• Primary goal is LDL-C reduction; triglyceride lowering is secondary benefit 2

Prescription Omega-3 Fatty Acids

• Icosapent ethyl 2-4 g/day can be added as adjunctive therapy for persistent hypertriglyceridemia despite lifestyle modifications 1, 2
• Indicated for patients with triglycerides ≥150 mg/dL and established cardiovascular disease or diabetes with ≥2 additional risk factors 3
• Monitor for increased risk of atrial fibrillation 3

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 3
• Do not start with statin monotherapy when triglycerides are ≥500 mg/dL - fibrates must be first-line 3
• Do not use bile acid sequestrants when triglycerides are >200 mg/dL - they are relatively contraindicated 3
• Monitor for myopathy risk when combining fibrates with statins, especially in patients >65 years; use lower statin doses to minimize risk 3
• Avoid gemfibrozil with statins - fenofibrate has a better safety profile for combination therapy 3

Monitoring and Follow-up

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications or starting pharmacotherapy 1, 2
• Withdraw therapy in patients who do not have adequate response after 2 months of treatment with maximum recommended dose 4
• Monitor for muscle symptoms and obtain baseline and follow-up CPK levels when using fibrates, especially in combination with statins 3