What is the best medication to lower hypertriglyceridemia?

Best Medication for Lowering Triglycerides

Fibrates, particularly fenofibrate, are considered the most potent triglyceride-lowering agents and should be the first-line pharmacological therapy for patients with severely elevated triglycerides (>500 mg/dL). 1

Treatment Algorithm Based on Triglyceride Levels

For Severely Elevated Triglycerides (≥500 mg/dL)

1. First choice: Fibrates (fenofibrate 54-160 mg daily or gemfibrozil 600 mg twice daily)

   • Can reduce triglycerides by up to 50% 1
   • Primary goal is to reduce risk of pancreatitis
   • Fenofibrate is preferred over gemfibrozil when combined with statins due to lower risk of myopathy 1

2. Alternative options:

   • Prescription omega-3 fatty acids (2-4 g/day) - can reduce triglycerides by up to 40% 1
   • Niacin (1-2 g/day) - can reduce triglycerides by up to 30% 1

For Moderate Hypertriglyceridemia (150-499 mg/dL)

1. First approach: Lifestyle modifications and addressing underlying causes

   • Optimize glycemic control in patients with diabetes
   • Weight reduction, physical activity, reduced alcohol consumption
   • Dietary changes: lower carbohydrates (especially refined), increase omega-3 fatty acids 2

2. Pharmacological therapy based on cardiovascular risk:

   • For patients with ASCVD or high cardiovascular risk: Statins first, then consider adding icosapent ethyl (purified EPA) if triglycerides remain elevated 1, 3
   • For patients with borderline or intermediate risk: Consider statin therapy 2

Efficacy of Different Medications

1. Fibrates:

   • Most potent triglyceride-lowering effect (up to 50% reduction) 1
   • Fenofibrate clinical trials show median triglyceride reduction of 60% 4
   • Fenofibrate at 400 mg/day can reduce VLDL-triglycerides by 65% in type IIB+IV patients 5
   • Also increase HDL cholesterol 6

2. Prescription Omega-3 fatty acids:

   • Reduce triglycerides by up to 40% 1
   • EPA-only formulations (icosapent ethyl) do not raise LDL cholesterol 3
   • EPA+DHA formulations may raise LDL cholesterol when used for very high triglycerides 3

3. Niacin:

   • Reduces triglycerides by up to 30% 1
   • May worsen insulin resistance and glycemic control 1
   • New data suggest it may increase risk of ASCVD 1

Special Considerations

• Diabetes: Improved glycemic control should be a priority for triglyceride lowering 1
• HIV patients on antiretroviral therapy: Fibrates are first-line for triglycerides >500 mg/dL 1
• Combination therapy: For refractory cases, combinations may be needed but use with caution:
  • Fibrate + statin increases risk of myopathy; pravastatin is preferred if this combination is necessary 1
  • Fibrate + omega-3 fatty acids may be considered for severe hypertriglyceridemia 1

Common Pitfalls and Caveats

• Statin-fibrate interaction: Risk of myopathy is increased when combining fibrates (especially gemfibrozil) with statins; fenofibrate has lower risk than gemfibrozil 1
• Niacin side effects: Flushing is common; may worsen glycemic control in diabetic patients 1
• Monitoring: Regular liver function tests are recommended with fibrate therapy 6
• Timing: If combining fibrates and statins, take fibrates in the morning and statins in the evening to minimize peak dose concentrations 1
• Treatment expectations: In real-world settings, only about 49% of patients reach triglyceride levels <150 mg/dL after fenofibrate therapy 4

For patients with acute, severe hypertriglyceridemia and hyperglycemia, more aggressive approaches may be needed, including extreme reduction of fat intake, insulin infusion, and in some cases, apheresis 1.