What is the management plan for a patient with hypercholesterolemia and hypertriglyceridemia?

Management of Hypercholesterolemia and Hypertriglyceridemia

Immediate Assessment and Classification

For patients with both elevated cholesterol and triglycerides, you must first classify the triglyceride severity to determine the treatment sequence, as this fundamentally changes your approach. 1

• Obtain at least two fasting lipid panels, preferably 2 weeks apart, to confirm the diagnosis and guide treatment decisions 2
• Classify triglyceride severity: Mild (150-199 mg/dL), Moderate (200-499 mg/dL), Severe (500-999 mg/dL), Very Severe (≥1,000 mg/dL) 1, 2
• Calculate non-HDL cholesterol (total cholesterol minus HDL-C) with a target goal of <130 mg/dL 1, 2
• Measure hemoglobin A1c and fasting glucose to assess for diabetes, as poor glycemic control is often the primary driver of severe hypertriglyceridemia 1, 3
• Check TSH to rule out hypothyroidism, assess renal function (serum creatinine and eGFR), and review all medications that may elevate triglycerides 1, 2

Treatment Algorithm Based on Triglyceride Level

If Triglycerides ≥500 mg/dL (Severe to Very Severe)

Initiate fenofibrate 54-160 mg daily immediately as first-line therapy to prevent acute pancreatitis, before addressing LDL cholesterol. 1, 3

• Fenofibrate reduces triglycerides by 30-50% and is mandatory at this level, as the risk of acute pancreatitis is 14% with severe hypertriglyceridemia 1, 3, 4
• 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 1, 3
• Implement aggressive dietary fat restriction to 20-25% of total daily calories for triglycerides 500-999 mg/dL, or 10-15% for triglycerides ≥1,000 mg/dL 1, 3
• Completely eliminate all added sugars and mandate complete alcohol abstinence, as alcohol can precipitate hypertriglyceridemic pancreatitis at these levels 1, 3
• Once triglycerides fall below 500 mg/dL with fenofibrate therapy, reassess LDL-C and initiate moderate-intensity statin therapy if LDL-C remains elevated or cardiovascular risk is high 1, 3

If Triglycerides 200-499 mg/dL (Moderate) with Elevated LDL-C

Initiate moderate-to-high intensity statin therapy as first-line if 10-year ASCVD risk is ≥7.5% or LDL-C is elevated, as statins address both lipid abnormalities and provide proven cardiovascular benefit. 1

• Statins provide 10-30% dose-dependent triglyceride reduction in addition to 30-50% LDL-C reduction 1
• Target LDL-C <100 mg/dL (or <70 mg/dL for very high-risk patients) and non-HDL-C <130 mg/dL 1
• Restrict added sugars to <6% of total daily calories and limit total dietary fat to 30-35% of total calories 1
• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, add prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) if the patient has established cardiovascular disease or diabetes with ≥2 additional risk factors 1

If Triglycerides 150-199 mg/dL (Mild) with Elevated LDL-C

Consider moderate-intensity statin therapy if 10-year ASCVD risk is ≥7.5%, as persistently elevated triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor. 1

• For patients with 10-year ASCVD risk 5% to <7.5%, engage in patient-clinician discussion regarding statin initiation 1
• Target 5-10% body weight reduction, which produces a 20% decrease in triglycerides—the single most effective lifestyle intervention 1
• Engage in ≥150 minutes/week of moderate-intensity aerobic activity, which reduces triglycerides by approximately 11% 1

Lifestyle Modifications (All Severity Levels)

• Target 5-10% weight loss, which can reduce triglycerides by 20% and in some patients up to 50-70% 1
• Restrict saturated fats to <7% of total energy intake, replacing with monounsaturated or polyunsaturated fats 1
• Increase soluble fiber to >10 g/day from sources like oats, beans, and vegetables 1
• Consume ≥2 servings (8+ ounces) per week of fatty fish rich in EPA and DHA (salmon, trout, sardines, anchovies) 1
• Limit or completely avoid alcohol consumption—even 1 ounce daily increases triglycerides by 5-10% 1

Combination Therapy Considerations

When combining fenofibrate with statins, use fenofibrate (NOT gemfibrozil) and lower statin doses to minimize myopathy risk, particularly in patients >65 years or with renal disease. 1

• Fenofibrate has a significantly better safety profile than gemfibrozil when combined with statins because it does not inhibit statin glucuronidation 1
• Monitor creatine kinase levels and muscle symptoms at baseline and follow-up, especially in elderly patients or those with renal disease 1
• Take fenofibrate in the morning and statins in the evening to minimize peak dose concentrations 1

Role of Icosapent Ethyl (Prescription Omega-3)

Add icosapent ethyl 2g twice daily to maximally tolerated statin therapy if triglycerides remain ≥150 mg/dL and the patient has established cardiovascular disease or diabetes with ≥2 additional risk factors. 5, 1

• The REDUCE-IT trial demonstrated a 25% reduction in major adverse cardiovascular events with icosapent ethyl (number needed to treat = 21) 5, 1
• Icosapent ethyl is the only triglyceride-lowering therapy FDA-approved for cardiovascular risk reduction 1
• Monitor for increased risk of atrial fibrillation with prescription omega-3 fatty acids 1

Monitoring Strategy

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications 1, 2
• Reassess lipids 4-8 weeks after initiating or adjusting pharmacotherapy 1, 2
• Monitor liver enzymes and creatine kinase if fenofibrate is added, particularly at baseline and 3 months after initiation 1
• Follow up every 6-12 months with fasting lipid panels once goals are achieved 1

Critical 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, 3
• Do NOT use gemfibrozil when combining with statins—fenofibrate has a significantly better safety profile 1
• Do NOT ignore secondary causes such as uncontrolled diabetes, hypothyroidism, or medications that elevate triglycerides, as treating these conditions may eliminate the need for lipid-lowering medications 1, 2, 3
• Do NOT use bile acid sequestrants when triglycerides are >200 mg/dL, as they are relatively contraindicated 1