What is the appropriate treatment for an adult patient with elevated triglycerides (hypertriglyceridemia)?

Treatment for Triglycerides of 298 mg/dL

Immediate Treatment Approach

For a triglyceride level of 298 mg/dL (moderate hypertriglyceridemia), initiate aggressive lifestyle modifications immediately and consider statin therapy if cardiovascular risk is elevated (10-year ASCVD risk ≥7.5%, diabetes age 40-75, or established cardiovascular disease). 1, 2

This triglyceride level falls into the moderate hypertriglyceridemia category (200-499 mg/dL), which is associated with increased cardiovascular risk but does not require immediate fibrate therapy to prevent pancreatitis—that threshold is ≥500 mg/dL. 1, 2

Lifestyle Modifications (First-Line for All Patients)

Weight Loss and Exercise:

• Target a 5-10% body weight reduction, which produces a 20% decrease in triglycerides—this is the single most effective lifestyle intervention. 1, 2
• Engage in at least 150 minutes per week of moderate-intensity aerobic activity, which reduces triglycerides by approximately 11%. 1, 2

Dietary Changes:

• Restrict added sugars to <6% of total daily calories, as sugar intake directly increases hepatic triglyceride production. 1, 2
• Limit total dietary fat to 30-35% of total calories for moderate hypertriglyceridemia. 1, 2
• Restrict saturated fats to <7% of total energy intake, replacing with monounsaturated or polyunsaturated fats. 1, 2
• Increase soluble fiber to >10 g/day from sources like oats, beans, and vegetables. 1
• Consume at least 2 servings per week of fatty fish (salmon, trout, sardines) rich in omega-3 fatty acids. 1

Alcohol Elimination:

• Limit or completely avoid alcohol consumption, as even 1 ounce daily increases triglycerides by 5-10%. 1, 2

Evaluate and Address Secondary Causes

Before initiating pharmacotherapy, evaluate for reversible causes: 1, 2

• Uncontrolled diabetes mellitus (check HbA1c and fasting glucose)—optimizing glucose control can reduce triglycerides by 20-50% independent of lipid medications. 1, 2
• Hypothyroidism (check TSH)—must be treated before expecting full response to lipid therapy. 1, 2
• Medications that raise triglycerides: thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, antipsychotics—discontinue or substitute if possible. 1
• Chronic kidney disease or liver disease (check creatinine, eGFR, AST, ALT). 1, 2

Pharmacologic Therapy Algorithm

Statin Therapy (First-Line if Cardiovascular Risk is Elevated):

• For patients aged 40-75 years with 10-year ASCVD risk ≥7.5%, diabetes, or established cardiovascular disease, initiate moderate-to-high intensity statin therapy (atorvastatin 10-20 mg or rosuvastatin 5-10 mg daily). 1, 2
• Statins provide 10-30% dose-dependent triglyceride reduction plus proven cardiovascular mortality benefit through LDL-C reduction. 1, 2, 3
• Target LDL-C <100 mg/dL and non-HDL-C <130 mg/dL. 1

Add-On Therapy if Triglycerides Remain >200 mg/dL After 3 Months:

• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, consider adding icosapent ethyl 2g twice daily (total 4g/day) if the patient has established cardiovascular disease OR diabetes with ≥2 additional cardiovascular risk factors. 1, 2
• Icosapent ethyl demonstrated a 25% reduction in major adverse cardiovascular events in the REDUCE-IT trial (number needed to treat = 21). 1, 2
• Monitor for increased risk of atrial fibrillation with icosapent ethyl. 1

Alternative Add-On: Fenofibrate:

• If icosapent ethyl criteria are not met, consider fenofibrate 54-160 mg daily, which provides 30-50% triglyceride reduction. 1, 2, 4
• When combining fenofibrate with statins, use lower statin doses to minimize myopathy risk, particularly in patients >65 years or with renal disease. 1, 2
• Use fenofibrate (NOT gemfibrozil) when combining with statins, as fenofibrate has a significantly better safety profile. 1, 2

Monitoring Strategy

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications. 1, 2
• Reassess lipids 4-8 weeks after initiating or adjusting statin therapy. 1, 2
• Monitor for muscle symptoms and consider baseline creatine kinase if combining fibrate with statin. 1, 2
• If renal function is impaired (eGFR 30-59 mL/min/1.73 m²), start fenofibrate at 54 mg daily and do not exceed this dose. 4

Treatment Goals

• Primary goal: Reduce triglycerides to <200 mg/dL (ideally <150 mg/dL) to reduce cardiovascular risk. 1, 2
• Secondary goal: Non-HDL-C <130 mg/dL. 1
• LDL-C goal: <100 mg/dL for patients with elevated cardiovascular risk (or <70 mg/dL for very high-risk patients). 1

Critical Pitfalls to Avoid

• Do NOT delay statin therapy while attempting lifestyle modifications alone in high-risk patients (diabetes, 10-year ASCVD risk ≥7.5%, or established cardiovascular disease)—pharmacotherapy and lifestyle changes should occur simultaneously. 1
• Do NOT use over-the-counter fish oil supplements expecting cardiovascular benefit—only prescription omega-3 fatty acids (icosapent ethyl) have proven cardiovascular outcomes benefit. 1
• Do NOT use gemfibrozil when combining with statins—it has significantly higher myopathy risk than fenofibrate. 1, 2
• Do NOT start with fibrate monotherapy at this triglyceride level—fibrates are reserved for triglycerides ≥500 mg/dL to prevent pancreatitis. 1, 2