What is the best medication for hypertriglyceridemia?

Best Medications for Elevated Triglycerides

For patients with hypertriglyceridemia, fibrates (fenofibrate or gemfibrozil) are the most effective first-line medications, followed by prescription-grade omega-3 fatty acids, particularly icosapent ethyl (IPE) for those with cardiovascular disease risk. 1, 2, 3

Treatment Algorithm Based on Triglyceride Levels

Mild to Moderate Hypertriglyceridemia (150-499 mg/dL)

1. First-line approach: Lifestyle modifications

   • Weight reduction (5-10% if overweight/obese)
   • Reduced intake of refined carbohydrates and sugars
   • Decreased alcohol consumption
   • Regular aerobic exercise (150+ minutes/week)
   • Reduced saturated fat intake (<7% of calories)

2. Pharmacological therapy:

   • If ASCVD risk ≥7.5% or established ASCVD: Start with statin therapy
   • If triglycerides remain elevated after statin therapy:
     • Add fenofibrate (48-145 mg daily) - preferred over gemfibrozil due to lower risk of myopathy when combined with statins 2, 3
     • For patients with established ASCVD or diabetes plus ≥2 risk factors: Consider icosapent ethyl (IPE) 2-4g daily 1

Severe Hypertriglyceridemia (≥500 mg/dL)

1. First-line medication: Fibrates

   • Fenofibrate 54-160 mg daily OR
   • Gemfibrozil 600 mg twice daily (take 30 minutes before meals) 1, 3

2. Alternative or add-on therapies:

   • Prescription omega-3 fatty acids (2-4g daily)
   • Niacin (use with caution due to potential ASCVD risk) 1, 2

Efficacy of Medications

Fibrates

• Most potent triglyceride-lowering agents, reducing levels by up to 50% 3, 4
• Fenofibrate clinical trials showed 46-54% reduction in triglycerides 3
• Also increase HDL-C by 15-25% 2

Omega-3 Fatty Acids

• Reduce triglycerides by up to 40% 1, 5
• Only icosapent ethyl (IPE) has demonstrated cardiovascular outcomes benefits in the REDUCE-IT trial 1
• Non-prescription fish oil supplements are not recommended for ASCVD risk reduction 1

Niacin

• Reduces triglycerides by up to 30% 4
• Use with caution due to potential increased risk of ASCVD 1
• May worsen insulin resistance 1

Special Considerations

Combination Therapy

• For severe hypertriglyceridemia, combination therapy may be necessary
• When combining fibrates with statins, fenofibrate is preferred over gemfibrozil due to lower risk of myopathy 2, 3

Monitoring

• Recheck lipid panel 4-12 weeks after initiating therapy
• Monitor for adverse effects:
  • Fibrates: myopathy, liver function abnormalities
  • Omega-3 fatty acids: increased risk of atrial fibrillation (3.1% vs 2.1% in REDUCE-IT trial) 1

Secondary Causes

• Address underlying conditions that may contribute to hypertriglyceridemia:
  • Optimize glycemic control in diabetes
  • Treat hypothyroidism
  • Modify medications that increase triglycerides
  • Reduce alcohol consumption

Treatment Goals

• Primary goal: Lower triglycerides to <150 mg/dL
• Secondary goal: Achieve non-HDL cholesterol level 30 mg/dL higher than LDL goal
• For severe hypertriglyceridemia (≥500 mg/dL): Primary goal is to reduce pancreatitis risk

Pitfalls to Avoid

• Don't rely solely on non-prescription fish oil supplements, as they lack proven cardiovascular benefits 1
• Don't use gemfibrozil with statins due to increased myopathy risk 2
• Don't overlook the importance of lifestyle modifications, which can reduce triglycerides by 20-30% and are the foundation of treatment 6, 7
• Don't forget to assess and address secondary causes of hypertriglyceridemia before initiating pharmacotherapy 2