What medication is recommended for a patient with hypertriglyceridemia?

Medication for Hypertriglyceridemia

Treatment Selection Based on Triglyceride Level

For severe to very severe hypertriglyceridemia (≥500 mg/dL), initiate fenofibrate 54-160 mg daily immediately as first-line therapy to prevent acute pancreatitis, regardless of LDL-C levels or cardiovascular risk. 1, 2

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

• Fenofibrate is the first-line medication, providing 30-50% triglyceride reduction and preventing pancreatitis risk, which occurs in 14% of patients at this level. 1, 2
• Start fenofibrate at 54-160 mg daily based on renal function (54 mg if eGFR 30-59 mL/min/1.73 m², up to 160 mg if eGFR ≥60). 1
• Do not start with statin monotherapy when triglycerides are ≥500 mg/dL—statins provide only 10-30% triglyceride reduction, which is insufficient for pancreatitis prevention. 1
• Once triglycerides fall below 500 mg/dL with fenofibrate, reassess LDL-C and add statin therapy if LDL-C is elevated or cardiovascular risk is high. 1, 2

Moderate Hypertriglyceridemia (200-499 mg/dL)

• Statins are first-line if there is elevated LDL-C or 10-year ASCVD risk ≥7.5%, providing 10-30% dose-dependent triglyceride reduction plus proven cardiovascular benefit. 1, 2
• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, add icosapent ethyl 2g twice daily for patients with established cardiovascular disease or diabetes with ≥2 additional risk factors (25% reduction in major adverse cardiovascular events, NNT=21). 1, 3
• Alternatively, consider fenofibrate 54-160 mg daily if icosapent ethyl criteria are not met. 1, 2

Mild Hypertriglyceridemia (150-199 mg/dL)

• For patients with 10-year ASCVD risk ≥7.5%, consider moderate-intensity statin therapy (atorvastatin 10-20 mg or rosuvastatin 5-10 mg daily). 1
• Persistently elevated nonfasting triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor favoring statin initiation. 1

Critical Lifestyle Interventions (All Levels)

• Target 5-10% weight loss, which produces a 20% triglyceride reduction—the single most effective intervention. 1, 2
• Completely eliminate alcohol for severe hypertriglyceridemia (≥500 mg/dL); limit to ≤1-2 drinks daily for men (≤1 for women) for moderate levels. 1, 2
• Restrict added sugars to <6% of total daily calories for mild-moderate levels; eliminate completely for severe levels. 1, 2
• Limit total dietary fat to 30-35% of calories for moderate levels; 20-25% for severe levels; 10-15% for very severe levels. 1, 2
• Engage in ≥150 minutes/week of moderate-intensity aerobic activity (reduces triglycerides by ~11%). 1, 2

Address Secondary Causes First

• Optimize glycemic control in diabetic patients—poor glucose control is often the primary driver of severe hypertriglyceridemia and may be more effective than additional medications. 1, 2
• Check TSH to rule out hypothyroidism. 1, 2
• Assess for medications that raise triglycerides (thiazides, beta-blockers, estrogen, corticosteroids, antiretrovirals, antipsychotics) and discontinue or substitute if possible. 1

Combination Therapy Considerations

• When combining fenofibrate with statins, use lower statin doses (atorvastatin 10-20 mg maximum) to minimize myopathy risk, particularly in patients >65 years or with renal disease. 1, 2
• Use fenofibrate, not gemfibrozil, when combining with statins—fenofibrate has a significantly better safety profile with lower myopathy risk. 1, 2
• Monitor creatine kinase levels and muscle symptoms at baseline and follow-up when using combination therapy. 1, 2

Niacin: Limited Role

• Niacin should generally not be used—it showed no cardiovascular benefit when added to statin therapy in the AIM-HIGH trial, with increased risk of new-onset diabetes and gastrointestinal disturbances. 1, 4
• Niacin is FDA-approved for severe hypertriglyceridemia presenting pancreatitis risk, but fibrates are preferred due to better safety profile. 4

Monitoring Strategy

• Reassess fasting lipid panel in 4-8 weeks after initiating or adjusting pharmacotherapy. 1, 2
• Target goals: triglycerides <200 mg/dL (ideally <150 mg/dL); non-HDL-C <130 mg/dL for moderate hypertriglyceridemia. 1, 2
• Monitor renal function within 3 months after fenofibrate initiation and every 6 months thereafter; discontinue if eGFR persistently <30 mL/min/1.73 m². 1

Common Pitfalls to Avoid

• Do not delay fibrate therapy while attempting lifestyle modifications alone when triglycerides are ≥500 mg/dL—pharmacologic intervention is mandatory to prevent pancreatitis. 1, 2
• Do not use over-the-counter fish oil as a substitute for prescription omega-3 formulations—they are not equivalent. 1
• Do not ignore secondary causes—uncontrolled diabetes, hypothyroidism, or medications may be driving the hypertriglyceridemia and should be addressed first. 1, 2