First-Line Treatment for Hypertriglyceridemia
Treatment Algorithm Based on Triglyceride Level
For severe hypertriglyceridemia (≥500 mg/dL), fibrates are the first-line pharmacologic therapy and must be initiated immediately to prevent acute pancreatitis, regardless of LDL cholesterol levels. 1, 2, 3
Severe to Very Severe Hypertriglyceridemia (≥500 mg/dL)
Initiate fenofibrate 54-200 mg daily immediately as first-line therapy before addressing LDL cholesterol, as triglyceride reduction takes priority over LDL lowering at this level to prevent pancreatitis. 1, 2, 3
Fenofibrate should be started at 54-160 mg daily with meals, with dosage individualized based on response at 4-8 week intervals. 3
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 severity level. 1, 2
Implement extreme dietary fat restriction (<5% of total calories for levels ≥1000 mg/dL, or 10-15% for 500-999 mg/dL) and completely eliminate added sugars and alcohol. 1, 2
Once triglycerides are reduced below 500 mg/dL with fenofibrate, then initiate or optimize statin therapy to address LDL-C and cardiovascular risk. 1, 2
Moderate Hypertriglyceridemia (200-499 mg/dL)
Statins are first-line pharmacologic therapy for moderate hypertriglyceridemia when LDL-C is elevated or 10-year ASCVD risk is ≥7.5%, as they address both LDL cholesterol and provide 10-30% triglyceride reduction. 1, 2
If triglycerides remain elevated >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, add prescription omega-3 fatty acids (icosapent ethyl 2-4 g/day). 1, 2
Fibrates (fenofibrate 54-160 mg daily or gemfibrozil 600 mg twice daily) are reasonable alternatives only when statins are not appropriate. 1, 2
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 as this represents a risk-enhancing factor for cardiovascular disease. 1, 2
Lifestyle interventions remain the cornerstone, targeting 5-10% weight loss which can reduce triglycerides by 20%. 1, 2
Essential Lifestyle Interventions (All Severity Levels)
Lifestyle modifications are mandatory first-line therapy for all patients with hypertriglyceridemia and should be implemented immediately alongside pharmacologic therapy in severe cases. 1, 2
Target 5-10% weight loss, which is associated with a 20% decrease in triglycerides and can reduce levels by up to 50-70% in some patients. 1, 2
Engage in at least 150 minutes/week of moderate-intensity or 75 minutes/week of vigorous aerobic activity. 1, 2
Restrict added sugars to <6% of total daily calories and limit total fat to 30-35% of total daily calories for mild to moderate hypertriglyceridemia. 1, 2
Limit or completely avoid alcohol consumption, as it significantly raises triglyceride levels. 1, 2
Low-carbohydrate diets are more effective at lowering triglycerides than low-fat diets. 2
Critical Secondary Causes to Address First
Before initiating pharmacologic therapy, evaluate and aggressively treat secondary causes, as optimizing these conditions may obviate the need for lipid medications. 2, 3
Optimize glycemic control in diabetic patients, as poor control is often the primary driver of severe hypertriglyceridemia and can dramatically reduce triglycerides independent of lipid-lowering medications. 1, 2
Evaluate and treat hypothyroidism, as this is a common contributory factor to hypertriglyceridemia. 2, 3
Assess for renal disease and liver disease, which can contribute to elevated triglycerides. 2
Review medications that may elevate triglycerides, including estrogen therapy, thiazide diuretics, and beta-blockers, and consider discontinuation if possible. 3
Address excessive alcohol intake and obesity before initiating drug therapy. 3
Important Clinical Pitfalls to Avoid
Never delay fibrate initiation while attempting lifestyle modifications alone in patients with triglyceride levels ≥500 mg/dL, as pharmacologic therapy is mandatory to prevent pancreatitis. 1, 2
Do not use bile acid sequestrants when triglycerides are >200 mg/dL, as they are relatively contraindicated and can worsen hypertriglyceridemia. 1
Exercise caution when combining fibrates with statins due to increased risk of myopathy; fenofibrate has a better safety profile than gemfibrozil for combination therapy. 1, 2
Monitor for increased risk of atrial fibrillation with prescription omega-3 fatty acids, particularly in patients at high risk for this arrhythmia. 1, 2
In patients with renal impairment, initiate fenofibrate at 54 mg daily and avoid use in severe renal impairment. 3
Adjunctive Therapies for Refractory Cases
Prescription omega-3 fatty acids (icosapent ethyl 2-4 g/day) can be added as adjunctive therapy if triglycerides remain elevated after fenofibrate and lifestyle optimization. 1, 2, 4
Icosapent ethyl is specifically indicated as an adjunct to maximally tolerated statin therapy to reduce cardiovascular risk in patients with triglycerides ≥150 mg/dL and established cardiovascular disease or diabetes with ≥2 additional risk factors. 1, 2
Over-the-counter fish oil supplements are not equivalent to prescription formulations and should not be substituted. 2
Niacin may be considered as an alternative agent but should be used with caution in patients with diabetes due to potential worsening of insulin resistance. 1