What are the treatment options for elevated triglyceride (hypertriglyceridemia) levels?

Treatment of Hypertriglyceridemia

Lifestyle modifications are the first-line treatment for hypertriglyceridemia, followed by pharmacologic therapy based on triglyceride severity, with fibrates being first-line for severe hypertriglyceridemia (≥500 mg/dL) and statins or omega-3 fatty acids for moderate hypertriglyceridemia with cardiovascular risk factors. 1, 2, 3

Classification of Hypertriglyceridemia

• Normal: <150 mg/dL 2
• Mild: 150-199 mg/dL 2
• Moderate: 200-499 mg/dL 2
• Severe: 500-999 mg/dL 2
• Very severe: ≥1000 mg/dL 2, 3

Initial Assessment

• Evaluate for secondary causes including excessive alcohol intake, uncontrolled diabetes, hypothyroidism, renal disease, liver disease, and medications (thiazides, beta-blockers, estrogen, corticosteroids) 2, 3
• Assess cardiovascular risk factors, including family history, central obesity, hypertension, and abnormal glucose metabolism 2
• Determine risk of pancreatitis, particularly with triglycerides ≥500 mg/dL 2

Lifestyle Interventions

• Weight loss is the most effective lifestyle intervention - target 5-10% weight loss, which can reduce triglycerides by 20% 1, 2, 3
• Some patients may experience up to 50-70% reduction in triglycerides with weight loss 1, 2
• Dietary modifications based on triglyceride levels:
  • For mild to moderate hypertriglyceridemia: limit total fat to 30-35% of daily calories 2, 3
  • For severe hypertriglyceridemia (500-999 mg/dL): restrict fat to 20-25% of daily calories and eliminate added sugars 2, 3
  • For very severe hypertriglyceridemia (≥1000 mg/dL): restrict fat to 10-15% of daily calories and eliminate added sugars 2, 3
• Restrict added sugars to <6% of total daily calories for mild to moderate hypertriglyceridemia 2, 3
• Low-carbohydrate diets are more effective at lowering triglycerides than low-fat diets 2
• Exercise: at least 150 minutes/week of moderate-intensity or 75 minutes/week of vigorous aerobic activity 2, 3
• Limit or completely avoid alcohol consumption, especially in patients with severe hypertriglyceridemia 2, 3, 4

Pharmacologic Therapy

For Severe Hypertriglyceridemia (≥500 mg/dL)

• Fibrates are first-line therapy to reduce the risk of pancreatitis 2, 3, 5
• Initial dose of fenofibrate is 54-160 mg per day, with maximum dose of 160 mg once daily 5
• Prescription omega-3 fatty acids can be used as adjunctive therapy 2, 3

For Moderate Hypertriglyceridemia (200-499 mg/dL)

• Statins are first-line if there is elevated LDL-C or increased cardiovascular risk, providing 10-30% reduction in triglycerides 2, 4
• Consider adding prescription omega-3 fatty acids (2-4g/day) if triglycerides remain elevated after 3 months of lifestyle modifications and statin therapy 2, 4
• Icosapent ethyl (prescription omega-3 fatty acid) is indicated as an adjunct to maximally tolerated statin therapy to reduce cardiovascular risk in patients with triglycerides ≥150 mg/dL and established cardiovascular disease or diabetes with ≥2 additional risk factors 1

Special Considerations

• Optimize glycemic control in patients with diabetes, as it can significantly improve triglyceride levels 2, 3
• Use caution when combining fibrates with statins due to increased risk of myositis, particularly in patients with liver disease 2, 4
• For patients with renal impairment, fenofibrate should be initiated at a lower dose (54 mg/day) 5
• Avoid fibrates in patients with severe renal impairment 5

Monitoring and Follow-up

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications or medication changes 2, 3
• For moderate hypertriglyceridemia, target non-HDL-C level 30 mg/dL higher than LDL goal 2, 4
• For severe hypertriglyceridemia, primary goal is to reduce triglycerides below 500 mg/dL to prevent pancreatitis 2, 4
• Consider discontinuing therapy if there is no adequate response after two months of treatment with maximum recommended dose 5

Common Pitfalls and Caveats

• Failing to address secondary causes before initiating pharmacologic therapy 2, 3
• Not implementing aggressive lifestyle modifications as first-line treatment 1, 2
• Using combination therapy (fibrate + statin) without appropriate monitoring for myopathy 2, 4
• Focusing solely on triglyceride levels without addressing overall cardiovascular risk 2, 6
• Inadequate follow-up to assess treatment response and adjust therapy accordingly 5