What is the treatment for hypertriglyceridemia?

Treatment of Hypertriglyceridemia

The treatment approach for hypertriglyceridemia is determined by the severity of triglyceride elevation: for severe hypertriglyceridemia (≥500 mg/dL), initiate fenofibrate 54-160 mg daily immediately to prevent acute pancreatitis; for moderate hypertriglyceridemia (200-499 mg/dL), implement aggressive 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 and Risk Stratification

Hypertriglyceridemia is classified by severity according to the American College of Cardiology: 1, 2

• 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

The primary risks differ by severity: mild to moderate hypertriglyceridemia increases cardiovascular disease risk, while severe and very severe levels (≥500 mg/dL) carry significant risk of acute pancreatitis. 1, 3

Initial Assessment for Secondary Causes

Before initiating treatment, evaluate for secondary causes that may be driving the hypertriglyceridemia: 1, 2, 4

• Uncontrolled diabetes mellitus (often the primary driver of severe hypertriglyceridemia) 1
• Hypothyroidism (check TSH) 1
• Excessive alcohol intake (even 1 ounce daily increases triglycerides by 5-10%) 1
• Medications: thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, antipsychotics 1, 4
• Renal disease and liver disease 1, 2
• Obesity and sedentary lifestyle 1

Optimizing glycemic control in diabetic patients can dramatically reduce triglycerides independent of lipid medications and may obviate the need for additional pharmacotherapy. 1, 4

Lifestyle Interventions

Lifestyle modifications are fundamental for all patients with hypertriglyceridemia and should be implemented before or concurrent with pharmacotherapy: 1, 2, 3

Weight Loss and Exercise

• Target 5-10% body weight reduction, which produces a 20% decrease in triglycerides (in some patients, up to 50-70% reduction). 1, 2
• Engage in at least 150 minutes/week of moderate-intensity aerobic activity (or 75 minutes/week vigorous activity), which reduces triglycerides by approximately 11%. 1, 2, 3

Dietary Modifications by Severity

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

• Restrict added sugars to <6% of total daily calories 1
• Limit total fat to 30-35% of total daily calories 1
• Restrict saturated fats to <7% of total calories 1
• Eliminate trans fats completely 1
• Increase soluble fiber to >10 g/day 1
• Consume ≥2 servings (8+ ounces) per week of fatty fish (salmon, trout, sardines) 1

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

• Restrict total dietary fat to 20-25% of total calories 1
• Eliminate all added sugars completely 1
• Prioritize lean fish over fatty fish when fat must be severely restricted 1

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

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

Alcohol Restriction

• Limit or avoid alcohol for mild to moderate hypertriglyceridemia 1, 2
• Complete abstinence from alcohol is mandatory for patients with severe hypertriglyceridemia (≥500 mg/dL) to prevent hypertriglyceridemic pancreatitis 1, 3, 5

Pharmacologic Therapy Algorithm

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

Immediate intervention is required to prevent acute pancreatitis: 1, 2, 4

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

Once triglycerides fall below 500 mg/dL: 1

• Reassess LDL-C and consider adding or optimizing statin therapy if LDL-C is elevated or cardiovascular risk is high 1
• Statins provide an additional 10-30% dose-dependent triglyceride reduction 1, 2

Adjunctive therapy if triglycerides remain elevated: 1

• Add prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) if triglycerides remain >200 mg/dL after 3 months of fenofibrate, lifestyle optimization, and statin therapy 1

Moderate Hypertriglyceridemia (200-499 mg/dL)

For patients with elevated LDL-C or increased cardiovascular risk: 1, 2

• Statins are first-line pharmacologic therapy, providing 10-30% dose-dependent triglyceride reduction and proven cardiovascular benefit. 1, 2
• Target non-HDL-C <130 mg/dL (calculated as total cholesterol minus HDL-C). 1

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

• 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
• Icosapent ethyl provides a 25% reduction in major adverse cardiovascular events (number needed to treat = 21). 1
• Monitor for increased risk of atrial fibrillation with icosapent ethyl. 1

Alternative option: 1

• Consider fenofibrate 54-160 mg daily if icosapent ethyl criteria are not met, providing 30-50% triglyceride reduction. 1

Mild Hypertriglyceridemia (150-199 mg/dL)

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

• Persistently elevated nonfasting triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor that favors statin initiation or intensification. 1
• Statins provide 10-30% triglyceride reduction and proven cardiovascular risk reduction. 1

For patients with 10-year ASCVD risk 5% to <7.5%: 1

• Consider patient-clinician discussion regarding statin initiation. 1

Combination Therapy Safety Considerations

When combining lipid-lowering medications, important safety considerations include: 1, 2

• The combination of high-dose statin with fibrates increases myopathy risk, particularly in patients >65 years or with renal disease. 1, 2
• Use lower statin doses (e.g., atorvastatin 10-20 mg maximum) when combining with fenofibrate to minimize myopathy risk. 1
• Fenofibrate has a better safety profile than gemfibrozil when combined with statins; gemfibrozil should be avoided. 1
• Monitor creatine kinase levels and muscle symptoms when using combination therapy. 1
• Consider taking fibrates in the morning and statins in the evening to minimize peak dose concentrations. 1

Monitoring and Follow-up

• Reassess fasting lipid panel in 4-8 weeks after implementing lifestyle modifications or initiating/adjusting pharmacotherapy. 1, 2
• Monitor liver function tests and creatine kinase if fenofibrate is added, particularly at baseline and 3 months after initiation. 1
• Therapy should be withdrawn in patients who do not have an adequate response after two months of treatment with the maximum recommended dose of fenofibrate 160 mg once daily. 4
• Once goals are achieved, follow-up every 6-12 months. 1

Critical Pitfalls to Avoid

• Do not delay fibrate initiation while attempting lifestyle modifications alone in patients with triglycerides ≥500 mg/dL, as pharmacologic therapy is mandatory to prevent pancreatitis. 1
• 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 overlook secondary causes, particularly uncontrolled diabetes and hypothyroidism, as addressing these may obviate the need for additional lipid medications. 1, 4
• Do not use over-the-counter fish oil supplements as a substitute for prescription omega-3 formulations, as they are not equivalent. 1
• Do not use bile acid sequestrants when triglycerides are >200 mg/dL, as they are relatively contraindicated. 1
• 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