What are the management options for elevated triglycerides?

Management of Elevated Triglycerides

Lifestyle interventions are the first-line therapy for all patients with elevated triglycerides, with pharmacologic therapy added based on triglyceride severity and cardiovascular risk. 1, 2

Classification and Risk Stratification

Triglyceride levels should be classified as follows to guide management 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

The primary concern shifts based on severity: moderate hypertriglyceridemia increases cardiovascular risk, while severe levels (≥500 mg/dL) significantly increase pancreatitis risk. 2, 4

Initial Assessment: Identify Secondary Causes

Before initiating treatment, evaluate and address secondary causes 2, 5:

• Metabolic factors: Uncontrolled diabetes, hypothyroidism, obesity, metabolic syndrome
• Lifestyle factors: Excessive alcohol intake, sedentary lifestyle, poor diet quality
• Medications: Thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids
• Organ dysfunction: Renal disease, liver disease

Optimizing glycemic control in diabetic patients often eliminates the need for triglyceride-specific pharmacotherapy. 2, 5

Lifestyle Interventions (All Patients)

Weight Loss

Weight loss is the single most effective lifestyle intervention for lowering triglycerides. 1, 2

• Target 5-10% body weight reduction, which typically lowers triglycerides by 20% 2, 3
• Some patients may achieve 50-70% triglyceride reduction with weight loss alone 1, 2

Dietary Modifications (Severity-Based)

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

• Restrict added sugars to <6% of total daily calories
• Limit total fat to 30-35% of total daily calories
• Low-carbohydrate diets are more effective than low-fat diets for triglyceride reduction 1, 2

For severe hypertriglyceridemia (500-999 mg/dL): 2, 6

• Eliminate added sugars completely
• Restrict dietary fat to 20-25% of total calories

For very severe hypertriglyceridemia (≥1,000 mg/dL): 2, 6

• Eliminate all added sugars
• Implement very low-fat diet (10-15% of total calories)
• Consider extreme fat restriction (<5% of calories) until levels drop below 1,000 mg/dL 2

Physical Activity and Alcohol

• Engage in 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 with severe hypertriglyceridemia 1, 2, 6

Pharmacologic Therapy: Algorithm by Triglyceride Level

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

Immediate pharmacologic intervention is mandatory to prevent acute pancreatitis. 2, 7

Primary therapy: Fibrates (first-line) 2, 3, 4

• Fenofibrate 54-160 mg daily (dose adjusted based on renal function and response) 5
• Can reduce triglycerides by 30-50% 2
• Fibrates or niacin should be initiated BEFORE LDL-lowering therapy when triglycerides are ≥500 mg/dL 2

Adjunctive therapy: 1, 2

• Add prescription omega-3 fatty acids (2-4g/day) if triglycerides remain elevated despite fibrate therapy
• Omega-3 preparations (EPA+DHA combinations) are FDA-approved for severe hypertriglyceridemia (≥500 mg/dL) 1

After triglycerides are reduced below 500 mg/dL: 2

• Initiate or optimize statin therapy to address LDL-C and cardiovascular risk
• Monitor lipid panel every 4-8 weeks initially 5

Moderate Hypertriglyceridemia (200-499 mg/dL)

Management depends on cardiovascular risk and LDL-C levels 2, 7:

If LDL-C is elevated or cardiovascular risk is high: 2, 3

• Initiate or optimize statin therapy (provides 10-30% triglyceride reduction)
• Calculate non-HDL-C (total cholesterol minus HDL-C); target <130 mg/dL 2, 7

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

• Consider adding prescription omega-3 fatty acids (2-4g/day), specifically icosapent ethyl for patients with established cardiovascular disease or diabetes with ≥2 additional risk factors on maximally tolerated statin 1, 2
• Alternative: Add fenofibrate if cardiovascular risk is high and triglycerides remain significantly elevated 2

Mild Hypertriglyceridemia (150-199 mg/dL)

• Focus on lifestyle interventions 2, 3
• Assess overall cardiovascular risk 2, 4
• Consider statin therapy if 10-year ASCVD risk is ≥7.5% 2

Special Considerations for Combination Therapy

When combining fibrates with statins: 2, 3

• Fenofibrate has a better safety profile than gemfibrozil when combined with statins
• Monitor for myopathy risk with baseline and follow-up creatine kinase levels 2
• Keep statin doses relatively low when combining with fibrates 2
• The combination increases myopathy risk, particularly in patients >65 years 2, 3

Icosapent ethyl (prescription EPA) specific indications: 1, 2

• FDA-approved as adjunct to maximally tolerated statin therapy for patients with triglycerides ≥150 mg/dL AND:
  • Established cardiovascular disease, OR
  • Diabetes mellitus with ≥2 additional cardiovascular risk factors
• Monitor for increased risk of atrial fibrillation 2

Critical Pitfalls to Avoid

• Do NOT delay fibrate initiation while attempting lifestyle modifications alone when triglycerides are ≥500 mg/dL—pharmacologic therapy is mandatory 2
• Do NOT start with statin monotherapy when triglycerides are ≥500 mg/dL—initiate fibrates first 2
• Do NOT use bile acid sequestrants when triglycerides are >200 mg/dL—they are relatively contraindicated 2
• Do NOT overlook glycemic control in diabetic patients—this can be more effective than additional medications 2
• Do NOT continue therapy if no adequate response after 2 months at maximum dose (fenofibrate 160 mg daily) 5

Monitoring and Follow-up

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications or starting pharmacotherapy 2, 3
• For patients on fibrates, monitor lipid levels every 4-8 weeks initially and adjust dosing based on response 5
• Evaluate for muscle symptoms and obtain creatine kinase levels when using fibrates, especially in combination with statins 2
• Adjust fenofibrate dosing in renal impairment: start at 54 mg daily in mild-moderate renal dysfunction; avoid in severe renal impairment 5