How do you treat elevated triglycerides (hypertriglyceridemia)?

Treatment of Elevated Triglycerides

Lifestyle interventions are first-line therapy for all patients with hypertriglyceridemia, but patients with triglycerides ≥500 mg/dL require immediate fibrate therapy to prevent acute pancreatitis, regardless of cardiovascular risk. 1, 2

Classification and Risk Stratification

Triglyceride levels determine treatment urgency 2, 3:

• Normal: <150 mg/dL
• Mild: 150-199 mg/dL
• Moderate: 200-499 mg/dL (cardiovascular risk focus)
• Severe: 500-999 mg/dL (pancreatitis risk begins)
• Very Severe: ≥1,000 mg/dL (high pancreatitis risk)

Initial Assessment: Identify Secondary Causes

Before starting treatment, aggressively evaluate and address 1, 4:

• Uncontrolled diabetes (most common driver—optimizing glucose control can dramatically reduce triglycerides independent of lipid medications) 1, 2
• Excessive alcohol intake (abstinence mandatory for severe hypertriglyceridemia) 1
• Hypothyroidism 4, 5
• Medications: thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, antipsychotics 2, 4
• Renal or liver disease 2, 5

Lifestyle Interventions (All Patients)

Weight Loss

Target 5-10% body weight reduction, which produces a 20% decrease in triglycerides (some patients achieve 50-70% reduction) 1, 2. This is the single most effective lifestyle intervention. 1

Dietary Modifications by Severity

For Mild-Moderate (150-499 mg/dL): 1, 2

• Restrict added sugars to <6% of total daily calories
• Limit total fat to 30-35% of total calories
• Prioritize low-carbohydrate diets over low-fat diets (more effective for triglyceride lowering) 1
• Very low-carbohydrate diets (<10% calories from carbs) produce greatest reduction: 24 mg/dL 1

For Severe (500-999 mg/dL): 2, 3

• Restrict total fat to 20-25% of total calories
• Eliminate all added sugars completely
• Complete alcohol abstinence

For Very Severe (≥1,000 mg/dL): 2, 3

• Extreme fat restriction: 10-15% of total calories (or <5% until levels drop below 1,000 mg/dL) 2
• Zero added sugars
• Zero alcohol

Fish Consumption

Consume ≥2 servings (8+ ounces) per week of fatty fish (salmon, trout, sardines, anchovies) for moderate hypertriglyceridemia 1. For severe cases requiring fat restriction, choose lean fish (cod, tilapia, flounder, shrimp). 1

Physical Activity

Engage in ≥150 minutes/week of moderate-intensity aerobic activity (or 75 minutes/week vigorous activity) 1, 2. Regular aerobic exercise reduces triglycerides by approximately 11%, while resistance training provides 6% reduction. 1

Alcohol

Complete abstinence for patients with severe hypertriglyceridemia (≥500 mg/dL) to prevent hypertriglyceridemic pancreatitis 1, 2. For moderate elevations, limit to standard recommendations, recognizing that 1 ounce/day increases triglycerides 5-10%. 1

Pharmacologic Therapy: Treatment Algorithm by Severity

Severe to Very Severe (≥500 mg/dL): IMMEDIATE FIBRATE THERAPY

Initiate fenofibrate immediately at 54-160 mg daily (maximum 160 mg daily) to prevent acute pancreatitis—this takes priority over LDL-lowering 2, 4. Do not delay for lifestyle modifications alone at this level. 2

• Fenofibrate reduces triglycerides by 30-50% 2
• Monitor lipids at 4-8 week intervals after initiation 4
• Once triglycerides fall below 500 mg/dL, reassess LDL-C and add statin therapy if elevated or cardiovascular risk is high 2
• Adjust fenofibrate dose based on renal function: start at 54 mg daily for mild-moderate renal impairment; avoid in severe renal impairment 4

Critical pitfall: Do NOT start with statin monotherapy when triglycerides ≥500 mg/dL—statins provide only 10-30% triglyceride reduction, insufficient for pancreatitis prevention. 2

Moderate (200-499 mg/dL): STATIN-BASED APPROACH

For patients with elevated LDL-C or 10-year ASCVD risk ≥7.5%: 2, 6

• Initiate or intensify statin therapy as first-line (provides 10-30% triglyceride reduction) 1, 6
• Target non-HDL-C <130 mg/dL 2

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

• Add prescription omega-3 fatty acids (icosapent ethyl 2-4 g/day) as adjunctive therapy 1, 2
• Icosapent ethyl is specifically indicated for patients with triglycerides ≥150 mg/dL on maximally tolerated statin with established cardiovascular disease OR diabetes with ≥2 additional risk factors 1
• Monitor for increased atrial fibrillation risk with omega-3 therapy 2

Alternative: Consider fenofibrate if cardiovascular risk is high and triglycerides remain significantly elevated despite statin therapy 2

Mild (150-199 mg/dL): RISK-BASED APPROACH

For patients with 10-year ASCVD risk 7.5-20% and persistently elevated nonfasting triglycerides ≥175 mg/dL: 2

• Consider initiating at least moderate-intensity statin therapy 2

For patients with 10-year ASCVD risk 5-7.5%: 2

• Engage in patient-clinician discussion regarding statin initiation 2

Combination Therapy Considerations

When combining fibrates with statins 2, 6:

• Fenofibrate has better safety profile than gemfibrozil when combined with statins 2
• Use lower statin doses to minimize myopathy risk (e.g., pravastatin 20-40 mg or atorvastatin 10 mg initially) 2
• Monitor creatine kinase levels and muscle symptoms, especially in patients >65 years or with renal disease 2
• Risk of clinical myositis appears low but requires vigilance 2

Prescription Omega-3 Fatty Acids: Specific Indications

Icosapent ethyl (EPA-only) or omega-3 acid ethyl esters (EPA+DHA) at 2-4 g/day 1, 7:

FDA-approved indications: 1

• Adjunct to maximally tolerated statin for patients with triglycerides ≥150 mg/dL AND established cardiovascular disease OR diabetes with ≥2 additional risk factors
• Adjunct to diet for severe hypertriglyceridemia (≥500 mg/dL)

Evidence: In REDUCE-IT trial, EPA-only (4 g/day) reduced major adverse cardiovascular events by 25% in high-risk statin-treated patients with hypertriglyceridemia 7

Important distinction: Over-the-counter fish oil supplements are NOT equivalent to prescription formulations and should not be substituted 2

Monitoring and Follow-Up

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications or starting pharmacotherapy 2, 3
• For patients on fenofibrate, repeat lipids at 4-8 week intervals until stable 4
• Withdraw therapy if no adequate response after 2 months at maximum dose (160 mg fenofibrate daily) 4
• Monitor liver transaminases every 3 months until normalization, then annually 2
• Once goals achieved, follow-up every 6-12 months 2

Special Populations

Diabetic patients: Aggressively optimize glycemic control first—this is often more effective than additional lipid medications for severe hypertriglyceridemia 1, 2

Elderly patients: Base fenofibrate dose selection on renal function 4

Renal impairment: Start fenofibrate at 54 mg daily for mild-moderate impairment; contraindicated in severe renal impairment 4

Common Pitfalls to Avoid

• Do not delay fibrate therapy while attempting lifestyle modifications alone when triglycerides ≥500 mg/dL 2
• Do not use bile acid sequestrants when triglycerides >200 mg/dL (relatively contraindicated) 2
• Do not overlook secondary causes, particularly uncontrolled diabetes and alcohol use 1, 2
• Do not substitute over-the-counter fish oil for prescription omega-3 formulations 2
• Do not combine gemfibrozil with statins—use fenofibrate instead for better safety profile 2, 6