What is the first line medication for a patient with hypertriglyceridemia?

First-Line Medication for High Triglycerides

For severe to very severe hypertriglyceridemia (≥500 mg/dL), fenofibrate is the first-line medication to prevent acute pancreatitis, while for moderate hypertriglyceridemia (200-499 mg/dL) with elevated cardiovascular risk, statins are first-line therapy. 1

Treatment Algorithm Based on Triglyceride Severity

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

Fenofibrate 54-160 mg daily should be initiated immediately as first-line therapy, before addressing LDL cholesterol, to prevent acute pancreatitis. 1 This level carries a 14% risk of acute pancreatitis and requires urgent pharmacologic intervention. 1

• Fenofibrate provides 30-50% triglyceride reduction. 1
• Statins alone are insufficient at this level, providing only 10-30% reduction. 1
• The primary goal is rapid reduction to <500 mg/dL to eliminate pancreatitis risk. 1

Critical pitfall: Do not start with statin monotherapy when triglycerides are ≥500 mg/dL—fibrates or niacin must be initiated before LDL-lowering therapy. 1

Moderate Hypertriglyceridemia (200-499 mg/dL)

For patients aged 40-75 years with 10-year ASCVD risk ≥7.5% or elevated LDL-C, initiate moderate-to-high intensity statin therapy as first-line. 1 Statins provide proven cardiovascular mortality benefit plus 10-30% dose-dependent triglyceride reduction. 1

• Target LDL-C <100 mg/dL and non-HDL-C <130 mg/dL. 1
• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, 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 demonstrated a 25% reduction in major adverse cardiovascular events (number needed to treat = 21). 1

Mild Hypertriglyceridemia (150-199 mg/dL)

Consider moderate-intensity statin therapy if 10-year ASCVD risk ≥7.5%, as persistently elevated triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor. 1

Alternative Consideration: Gemfibrozil

One guideline suggests gemfibrozil 600 mg twice daily as first-line for triglycerides ≥1500 mg/dL, with 44-54% reduction in triglyceride levels. 2 However, fenofibrate is strongly preferred over gemfibrozil when combining with statins due to significantly lower myopathy risk, as gemfibrozil inhibits statin glucuronidation. 1

FDA-Approved Indications

Prescription omega-3 fatty acids (such as Lovaza) are FDA-approved as adjunct to diet for severe hypertriglyceridemia (≥500 mg/dL), but the effect on pancreatitis risk has not been determined. 3

Niacin is FDA-approved as adjunctive therapy for severe hypertriglyceridemia presenting pancreatitis risk, but addition of niacin to statins did not reduce cardiovascular morbidity or mortality in the AIM-HIGH trial. 4

Essential Concurrent Interventions

Before initiating pharmacotherapy, aggressively evaluate and treat secondary causes: 1

• Optimize glycemic control in diabetic patients—poor glucose control can drive severe hypertriglyceridemia and improving control can reduce triglycerides by 20-50% independent of medications. 1
• Check TSH to rule out hypothyroidism. 1
• Mandate complete alcohol abstinence for severe hypertriglyceridemia (≥500 mg/dL), as even 1 ounce daily increases triglycerides by 5-10% and can precipitate pancreatitis. 1
• Discontinue or substitute medications that raise triglycerides (thiazides, beta-blockers, estrogen, corticosteroids, antiretrovirals, antipsychotics). 1

Safety Monitoring

When combining fenofibrate with statins (after triglycerides fall below 500 mg/dL), use lower statin doses to minimize myopathy risk, particularly in patients >65 years or with renal disease. 1 Monitor creatine kinase levels and muscle symptoms. 1 Check renal function within 3 months after fenofibrate initiation and every 6 months thereafter. 1