How to manage a patient with elevated cholesterol and triglycerides?

Management of Combined Hyperlipidemia: Cholesterol 265 mg/dL and Triglycerides 538 mg/dL

Immediate Priority: Prevent Acute Pancreatitis

Initiate fenofibrate 54-160 mg daily immediately as first-line therapy to reduce the risk of acute pancreatitis, as triglycerides ≥500 mg/dL require urgent pharmacologic intervention before addressing LDL cholesterol. 1, 2

• Your patient's triglyceride level of 538 mg/dL places them at significant risk for acute pancreatitis (14% incidence in patients with severe hypertriglyceridemia), and this risk escalates dramatically as levels approach 1,000 mg/dL 2
• Fenofibrate reduces triglycerides by 30-50% and is the preferred fibrate due to its better safety profile compared to gemfibrozil when later combined with statins 1, 2, 3
• Do not start with statin monotherapy at this triglyceride level—statins provide only 10-30% triglyceride reduction and are insufficient for preventing pancreatitis when triglycerides are ≥500 mg/dL 1, 2

Critical Dietary Interventions (Start Immediately)

Implement a very-low-fat diet restricting total fat to 20-25% of total daily calories and completely eliminate all added sugars and alcohol. 1, 2

• Complete alcohol abstinence is mandatory—alcohol synergistically increases triglycerides and can precipitate hypertriglyceridemic pancreatitis at these levels 1, 2
• Eliminate all added sugars completely, as sugar intake directly increases hepatic triglyceride production 1, 2
• Target a 5-10% body weight reduction, which produces a 20% decrease in triglycerides and is the single most effective lifestyle intervention 1, 2
• Engage in at least 150 minutes per week of moderate-intensity aerobic activity, which reduces triglycerides by approximately 11% 1, 2

Assess and Treat Secondary Causes

Aggressively evaluate for uncontrolled diabetes mellitus, hypothyroidism, renal disease, and medications that raise triglycerides. 1, 2

• Poor glycemic control is often the primary driver of severe hypertriglyceridemia—optimizing glucose control can dramatically reduce triglycerides independent of lipid medications 1, 2
• Check TSH to rule out hypothyroidism, assess renal function (creatinine, eGFR), and review medications including thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, and antipsychotics 1, 2
• If diabetes is present with poor control, treating hyperglycemia should be prioritized first, then hypertriglyceridemia should be re-evaluated 1

Add Statin Therapy Once Triglycerides Fall Below 500 mg/dL

Once triglycerides are reduced below 500 mg/dL with fenofibrate and lifestyle modifications, initiate moderate-to-high intensity statin therapy (atorvastatin 20-40 mg or rosuvastatin 10-20 mg daily) to address LDL cholesterol and cardiovascular risk. 1, 2, 4

• With total cholesterol of 265 mg/dL and triglycerides of 538 mg/dL, the estimated LDL-C is approximately 118-130 mg/dL (using Friedewald equation: Total-C minus HDL-C minus TG/5, assuming HDL-C ~35-40 mg/dL) 1
• The LDL-C goal is <100 mg/dL for high-risk patients, or <70 mg/dL if the patient has established cardiovascular disease 1
• When combining fenofibrate with statins, use lower statin doses initially (atorvastatin 10-20 mg maximum) to minimize myopathy risk, particularly in patients >65 years or with renal disease 1, 2

Consider Adding Prescription Omega-3 Fatty Acids

If triglycerides remain >200 mg/dL after 3 months of fenofibrate, lifestyle optimization, and statin therapy, add prescription omega-3 fatty acids (icosapent ethyl 2-4 g daily). 1, 2

• Icosapent ethyl is specifically indicated for patients with triglycerides ≥150 mg/dL on maximally tolerated statin with 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, 2
• Monitor for increased risk of atrial fibrillation with prescription omega-3 fatty acids 1, 2

Monitoring Strategy

Reassess fasting lipid panel in 4-8 weeks after initiating fenofibrate to confirm triglycerides are falling below 500 mg/dL. 1, 2

• Calculate non-HDL cholesterol (total cholesterol minus HDL cholesterol) with a target goal of <130 mg/dL for moderate hypertriglyceridemia 1, 2
• Monitor liver function tests (AST/ALT) and creatine kinase at baseline and 3 months after initiating fenofibrate, especially if combining with statins 1, 2
• Once triglycerides are <200 mg/dL and LDL-C is at goal, follow-up lipid panels every 6-12 months 1, 2

Critical Pitfalls to Avoid

• Do not delay fenofibrate initiation while attempting lifestyle modifications alone—pharmacologic therapy is mandatory when triglycerides are ≥500 mg/dL 1, 2
• Do not use gemfibrozil instead of fenofibrate—gemfibrozil has significantly higher myopathy risk when combined with statins and should be avoided 1, 2
• Do not ignore secondary causes—uncontrolled diabetes, hypothyroidism, or certain medications may be the primary driver and must be addressed 1, 2
• Do not combine high-dose statin with fibrate initially—this significantly increases myopathy risk; start with lower statin doses when combining 1, 2