What medications are used to treat hypertriglyceridemia?

Medications for Hypertriglyceridemia

Treatment Algorithm Based on Triglyceride Level

For severe to very severe hypertriglyceridemia (≥500 mg/dL), initiate fenofibrate immediately as first-line therapy to prevent acute pancreatitis, regardless of LDL cholesterol levels. 1

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

• Fenofibrate 54-200 mg daily is the first-line medication, providing 30-50% triglyceride reduction and preventing pancreatitis risk. 1
• Do not start with statin monotherapy at this level, as statins provide only 10-30% triglyceride reduction and are insufficient for pancreatitis prevention. 1
• Once triglycerides fall below 500 mg/dL with fenofibrate, add statin therapy if LDL-C is elevated or cardiovascular risk is high. 1
• Prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) can be added as adjunctive therapy if triglycerides remain elevated after fenofibrate and lifestyle optimization. 1

Moderate Hypertriglyceridemia (200-499 mg/dL)

• Statins are first-line therapy if there is elevated LDL-C or increased cardiovascular risk, providing 10-30% triglyceride reduction with proven cardiovascular benefit. 1
• If triglycerides remain >200 mg/dL after 3 months of optimized statin therapy and lifestyle modifications, add icosapent ethyl 2-4g daily. 1
• Fenofibrate can be considered for patients with LDL cholesterol 100-129 mg/dL and HDL <40 mg/dL. 2
• Target non-HDL-C <130 mg/dL in this range. 1

Mild Hypertriglyceridemia (150-199 mg/dL)

• For patients with 10-year ASCVD risk 7.5% to <20% and persistently elevated nonfasting triglycerides ≥175 mg/dL, consider statin initiation. 1
• Lifestyle modifications remain the cornerstone, with weight loss of 5-10% producing 20% triglyceride reduction. 1

Specific Medication Details

Fibrates

• Fenofibrate is preferred over gemfibrozil when combining with statins due to better safety profile. 1
• Gemfibrozil is contraindicated with simvastatin due to severe myopathy risk. 3
• When combining fibrates with statins, use lower statin doses (pravastatin 20-40 mg or atorvastatin 10 mg) to minimize myopathy risk, particularly in patients >65 years. 1
• Monitor creatine kinase levels and muscle symptoms with combination therapy. 1

Prescription Omega-3 Fatty Acids

• 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
• Provides 25% reduction in major adverse cardiovascular events when added to statin therapy. 1
• Monitor for increased risk of atrial fibrillation. 1
• Over-the-counter fish oil supplements are not equivalent to prescription formulations. 1

Statins

• High-dose statins (simvastatin 80 mg or atorvastatin 40-80 mg) can be moderately effective at reducing triglycerides but should be restricted to patients with both high LDL cholesterol and high triglycerides. 2
• Provide dose-dependent triglyceride reduction of 10-30%. 1

Niacin

• Should generally not be used, as it showed no cardiovascular benefit when added to statin therapy, with increased risk of new-onset diabetes and gastrointestinal disturbances. 1
• In diabetic patients, restrict to 2 g/day if used; short-acting nicotinic acid is preferred. 2

Critical Considerations Before Pharmacotherapy

• Optimize glycemic control first in diabetic patients, as poor glucose control is often the primary driver of severe hypertriglyceridemia and can be more effective than additional lipid medications. 1
• Evaluate and treat secondary causes: uncontrolled diabetes, hypothyroidism, renal disease, liver disease, excessive alcohol intake, and offending medications (thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, antipsychotics). 1
• Complete alcohol abstinence is mandatory for severe hypertriglyceridemia (≥500 mg/dL) to prevent hypertriglyceridemic pancreatitis. 1

Common Pitfalls to Avoid

• Do not delay fibrate initiation while attempting lifestyle modifications alone when triglycerides are ≥500 mg/dL—pharmacologic therapy is mandatory. 1
• Do not reduce fenofibrate or statin doses in patients with severe hypertriglyceridemia who need maximum lipid-lowering therapy. 1
• Do not overlook glycemic control optimization in diabetic patients before adding additional lipid medications. 1
• Avoid bile acid sequestrants when triglycerides are >200 mg/dL, as they are relatively contraindicated. 1