What is the most appropriate next step in management for a patient with significantly elevated triglycerides (hypertriglyceridemia), normal low-density lipoprotein (LDL) cholesterol, and borderline low high-density lipoprotein (HDL) cholesterol?

Management of Moderate Hypertriglyceridemia (300 mg/dL)

For this patient with triglycerides of 300 mg/dL, normal LDL cholesterol, and no cardiovascular disease history, initiate statin therapy as first-line pharmacologic treatment. 1, 2

Rationale for Statin as First-Line Therapy

• Statins are the recommended first-line pharmacologic therapy for moderate hypertriglyceridemia (200-499 mg/dL) because they simultaneously reduce triglycerides by 10-30% in a dose-dependent manner while providing proven cardiovascular risk reduction. 1, 2

• A triglyceride level of 300 mg/dL falls into the moderate hypertriglyceridemia category where the primary concern is atherosclerotic cardiovascular disease risk, not acute pancreatitis risk (which becomes relevant at ≥500 mg/dL). 1, 2

• The American College of Cardiology recommends statins for adults 40-75 years with moderate hypertriglyceridemia (150-499 mg/dL) and ASCVD risk ≥7.5%, with persistently elevated triglycerides favoring statin initiation or intensification. 1

• Even with ASCVD risk 5-7.5%, statin initiation should be considered given the triglyceride elevation. 2

Why NOT the Other Options

Omega-3 fatty acids (Option B): Prescription omega-3 fatty acids (icosapent ethyl) are indicated as adjunctive therapy to maximally tolerated statin therapy, not as first-line monotherapy. 1, 2 They should only be added if triglycerides remain >200 mg/dL after 3 months of optimized statin therapy and lifestyle modifications. 1, 2

Niacin (Option C): Niacin is not recommended as first-line therapy in current guidelines for moderate hypertriglyceridemia due to lack of robust cardiovascular outcomes data and significant tolerability issues, particularly in diabetic patients. 1

Fibrates/Clofibrate (Option D): Fibrates are reserved as first-line therapy for severe to very severe hypertriglyceridemia (≥500 mg/dL) to prevent acute pancreatitis. 3 For moderate hypertriglyceridemia with normal LDL, fibrates would only be considered after statin therapy has been optimized. 3

Clinical Algorithm for This Patient

Before initiating therapy:

• Screen for secondary causes including excessive alcohol intake, uncontrolled diabetes, hypothyroidism, renal disease, liver disease, and triglyceride-raising medications. 3, 2
• Calculate 10-year atherosclerotic cardiovascular disease risk using pooled cohort equations. 1, 2

Initial pharmacologic therapy:

• Start moderate-intensity statin therapy: atorvastatin 10-20 mg or rosuvastatin 5-10 mg daily. 2

Concurrent lifestyle modifications:

• Target 5-10% weight loss, which can reduce triglycerides by 20%. 3, 1
• Restrict added sugars to <6% of total daily calories and limit total fat to 30-35% of total daily calories. 3, 2
• Recommend at least 150 minutes/week of moderate-intensity aerobic activity. 3, 1
• Limit or completely avoid alcohol consumption. 3, 2

Monitoring and follow-up:

• Recheck fasting lipid panel after 3 months of statin therapy and lifestyle modifications. 2
• If triglycerides remain >200 mg/dL after optimized therapy, consider adding prescription omega-3 fatty acids (icosapent ethyl 2-4g/day). 1, 2
• Monitor for statin-associated side effects, particularly muscle symptoms. 1

Common Pitfalls to Avoid

• Do not delay statin initiation while attempting lifestyle modifications alone in patients with significant cardiovascular risk – pharmacologic therapy and lifestyle modifications should be implemented concurrently. 1

• Do not start with fibrates for moderate hypertriglyceridemia – fibrates are first-line only when triglycerides ≥500 mg/dL to prevent pancreatitis. 3

• Do not use omega-3 fatty acids as monotherapy – they are adjunctive to statin therapy, not first-line treatment. 1, 2