What medication specifically treats hypertriglyceridemia?

Medications That Specifically Target Hypertriglyceridemia

Fibrates (particularly fenofibrate) are the medications that specifically and most effectively treat isolated hypertriglyceridemia, reducing triglycerides by 30-50% and serving as first-line therapy when triglycerides exceed 500 mg/dL to prevent acute pancreatitis. 1

Primary Triglyceride-Lowering Agents

Fibrates: First-Line for Isolated Hypertriglyceridemia

Fenofibrate is the drug of choice for treating hypertriglyceridemia specifically, particularly when triglycerides are ≥500 mg/dL, as it provides 30-50% triglyceride reduction and has a better safety profile than gemfibrozil when combined with statins. 2, 1

• Fenofibrate dosing ranges from 54-200 mg daily, with dose adjustments based on renal function 1, 3
• Gemfibrozil should be avoided in diabetic patients and when combining with statins due to increased myopathy risk 2
• Fibrates work by activating peroxisome proliferator-activated receptor alpha (PPAR-α), which increases lipoprotein lipase activity and reduces hepatic triglyceride production 3

Prescription Omega-3 Fatty Acids: Adjunctive Therapy

Icosapent ethyl (prescription EPA) at 2-4 g/day is indicated as adjunctive therapy to statins for patients with triglycerides ≥150 mg/dL and 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

Niacin: Limited Current Role

Niacin is FDA-approved for severe hypertriglyceridemia but should generally not be used, as the AIM-HIGH trial showed no cardiovascular benefit when added to statin therapy, with increased risk of new-onset diabetes. 1, 4

• Low doses (≤2 g/day) may be considered in select diabetic patients with caution 2
• Flushing is the main adverse effect limiting compliance 2
• Can increase HDL cholesterol by 15-35% and lower triglycerides by 20-50% 5

Treatment Algorithm by Triglyceride Level

Severe to Very Severe (≥500 mg/dL)

Initiate fenofibrate 54-200 mg daily immediately as first-line therapy before addressing LDL cholesterol to prevent acute pancreatitis. 2, 1

• Implement extreme dietary fat restriction (10-15% of total calories for ≥1000 mg/dL; 20-25% for 500-999 mg/dL) 1
• Completely eliminate alcohol and added sugars 1
• Aggressively optimize glycemic control in diabetic patients, as this may be more effective than additional medications 2, 1
• Add prescription omega-3 fatty acids (2-4 g/day) as adjunctive therapy if triglycerides remain elevated 1

Moderate (200-499 mg/dL)

If LDL-C is also elevated or cardiovascular risk is high (≥7.5% 10-year ASCVD risk), start with statins as first-line therapy, which provide 10-30% triglyceride reduction. 1

• If triglycerides remain >200 mg/dL after 3 months of optimized statin therapy and lifestyle modifications, add prescription omega-3 fatty acids (icosapent ethyl 2-4 g/day) 1
• Consider fenofibrate if triglycerides remain significantly elevated and cardiovascular risk is high 2, 1

Mild (150-199 mg/dL)

For patients with 10-year ASCVD risk ≥7.5%, statins are first-line therapy, providing modest triglyceride reduction along with proven cardiovascular benefit. 1

• Persistently elevated nonfasting triglycerides ≥175 mg/dL is a risk-enhancing factor favoring statin initiation 1

Critical Safety Considerations

Combination Therapy Risks

When combining fenofibrate with statins, use lower statin doses to minimize myopathy risk, particularly in patients >65 years or with renal disease. 2, 1

• Fenofibrate has a better safety profile than gemfibrozil when combined with statins 2
• Monitor creatine kinase levels and muscle symptoms 2
• Take fibrates in the morning and statins in the evening to minimize peak dose concentrations 2

Monitoring Requirements

• Measure transaminases (AST/ALT) at baseline and periodically during treatment 1, 3
• Reassess lipid panel 4-8 weeks after initiating or adjusting fenofibrate 1
• Monitor renal function, as fenofibrate is renally excreted 3

Common Pitfalls to Avoid

Do not start with statin monotherapy when triglycerides are ≥500 mg/dL, as statins provide only 10-30% triglyceride reduction and are insufficient for preventing pancreatitis at this level. 1

Do not delay fibrate initiation while attempting lifestyle modifications alone in patients with triglycerides ≥500 mg/dL, as pharmacologic therapy is mandatory to prevent acute pancreatitis. 1

Do not use gemfibrozil in combination with statins due to significantly increased myopathy risk compared to fenofibrate. 2

Do not overlook secondary causes such as uncontrolled diabetes, hypothyroidism, excessive alcohol intake, or medications (thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals) before initiating drug therapy. 1, 5