What is the treatment for elevated triglycerides?

Treatment for Elevated Triglycerides

The treatment approach for elevated triglycerides depends critically on the severity level: for severe hypertriglyceridemia (≥500 mg/dL), initiate fenofibrate 54-160 mg daily immediately to prevent acute pancreatitis; for moderate hypertriglyceridemia (200-499 mg/dL), intensify lifestyle modifications and optimize statin therapy if cardiovascular risk is elevated, then consider adding icosapent ethyl 2-4g daily if triglycerides remain >200 mg/dL after 3 months; for mild hypertriglyceridemia (150-199 mg/dL), focus on lifestyle interventions and consider statin therapy if 10-year ASCVD risk is ≥7.5%. 1, 2

Classification-Based Treatment Algorithm

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

Immediate pharmacologic intervention is mandatory at this level to prevent acute pancreatitis, which occurs in 14% of patients with severe hypertriglyceridemia. 1

• Start fenofibrate 54-160 mg daily immediately as first-line therapy, before addressing LDL cholesterol, providing 30-50% triglyceride reduction 1, 2, 3
• Implement extreme dietary fat restriction to 10-15% of total calories for very severe hypertriglyceridemia (≥1000 mg/dL), or 20-25% for severe hypertriglyceridemia (500-999 mg/dL) 1, 2
• Completely eliminate all added sugars and alcohol, as these directly increase hepatic triglyceride production and can precipitate hypertriglyceridemic pancreatitis 1, 2
• Aggressively evaluate and treat secondary causes, particularly uncontrolled diabetes mellitus, as poor glycemic control is often the primary driver and optimizing glucose control can dramatically reduce triglycerides independent of lipid medications 1, 2
• Once triglycerides fall below 500 mg/dL, reassess LDL-C and consider adding statin therapy if LDL-C is elevated or cardiovascular risk is high 1

Moderate Hypertriglyceridemia (200-499 mg/dL)

• Initiate or intensify statin therapy if LDL-C is elevated or 10-year ASCVD risk is ≥7.5%, which provides 10-30% dose-dependent triglyceride reduction plus proven cardiovascular benefit 1, 2
• Target a 5-10% body weight reduction, which produces a 20% decrease in triglycerides as the single most effective lifestyle intervention 1, 2
• Restrict added sugars to <6% of total daily calories and limit total fat to 30-35% of total daily calories 1, 2
• Restrict saturated fats to <7% of total calories, replacing with monounsaturated or polyunsaturated fats 1
• Engage in ≥150 minutes/week of moderate-intensity aerobic activity, which reduces triglycerides by approximately 11% 1, 2
• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and maximally tolerated statin therapy, add icosapent ethyl 2-4g daily for patients with established cardiovascular disease OR diabetes with ≥2 additional risk factors 1, 2
• Target a secondary goal of non-HDL-C <130 mg/dL (calculated as total cholesterol minus HDL-C) 1

Mild Hypertriglyceridemia (150-199 mg/dL)

• Focus primarily on lifestyle interventions: weight loss, dietary modifications, and increased physical activity 1, 2
• Consider initiating moderate-intensity statin therapy for patients with 10-year ASCVD risk ≥7.5% or persistently elevated nonfasting triglycerides ≥175 mg/dL, as this constitutes a cardiovascular risk-enhancing factor 1, 2
• For patients with ASCVD risk 5% to <7.5%, engage in patient-clinician discussion regarding statin initiation 1

Critical Secondary Causes to Address First

• Uncontrolled diabetes mellitus: Optimize glycemic control with target HgA1C <7%, as this can reduce triglycerides more effectively than additional lipid medications in many cases 1
• Hypothyroidism: Check TSH and treat if elevated 1
• Excessive alcohol consumption: Even 1 ounce per day increases triglycerides by 5-10%; complete abstinence is mandatory for severe hypertriglyceridemia 1
• Medications that raise triglycerides: Discontinue or substitute thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, and antipsychotics if possible 1
• Chronic kidney disease, nephrotic syndrome, and chronic liver disease 1

Specific Pharmacologic Agents

Fibrates (First-Line for Severe Hypertriglyceridemia)

• Fenofibrate 54-160 mg daily is preferred over gemfibrozil when combining with statins, as fenofibrate has a better safety profile with lower myopathy risk 1, 3
• Gemfibrozil should be avoided when combining with statins due to significantly higher myopathy risk 1, 4
• 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
• Monitor creatine kinase levels and muscle symptoms at baseline and during treatment 1

Icosapent Ethyl (Prescription Omega-3 for Cardiovascular Risk Reduction)

• Icosapent ethyl 2g twice daily is specifically indicated as adjunct to maximally tolerated statin therapy for patients with triglycerides ≥150 mg/dL who have established cardiovascular disease OR diabetes with ≥2 additional risk factors 1, 2
• The REDUCE-IT trial demonstrated a 25% reduction in major adverse cardiovascular events (number needed to treat = 21) 1, 5, 6
• Monitor for increased risk of atrial fibrillation (3.1% hospitalization rate vs. 2.1% on placebo) 1, 2
• Over-the-counter fish oil supplements are not equivalent to prescription formulations and should not be substituted 1

Statins (For Moderate Hypertriglyceridemia with Elevated Cardiovascular Risk)

• Provide 10-30% dose-dependent triglyceride reduction in addition to proven cardiovascular benefit 1, 2
• Should be restricted to patients with both elevated LDL cholesterol and elevated triglycerides, or those with elevated cardiovascular risk 1
• High-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) provides ≥50% LDL-C reduction 1

Common Pitfalls to Avoid

• Do not delay fibrate therapy while attempting lifestyle modifications alone in patients with triglycerides ≥500 mg/dL—pharmacologic therapy is mandatory to prevent pancreatitis 1, 2
• Do not start with statin monotherapy when triglycerides are ≥500 mg/dL—statins provide only 10-30% triglyceride reduction and are insufficient for preventing pancreatitis at this level 1, 2
• Do not use gemfibrozil instead of fenofibrate when combining with statins—gemfibrozil has significantly higher myopathy risk 1, 4
• Do not ignore secondary causes such as uncontrolled diabetes or hypothyroidism—treating these can dramatically reduce triglycerides independent of lipid medications 1
• Do not use niacin routinely—it showed no cardiovascular benefit when added to statin therapy and increases risk of new-onset diabetes 1
• Do not use over-the-counter fish oil as a substitute for prescription omega-3 fatty acids—only prescription formulations have proven cardiovascular benefit 1

Monitoring Strategy

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications 1
• Reassess lipids 4-8 weeks after initiating or adjusting pharmacologic therapy 1
• Monitor liver function tests and creatine kinase if fibrates are added, particularly at baseline and 3 months after initiation 1
• Once goals are achieved, follow-up every 6-12 months 1