What medication should be added to a patient with dyslipidemia, normal cholesterol levels, and mildly elevated triglycerides, who is already taking a high-dose statin, to decrease cardiovascular risk?

Add Fibrates to High-Dose Statin Therapy

For a patient with dyslipidemia on high-dose statin therapy who has normal cholesterol, mildly elevated triglycerides, and no provided LDL value, add fenofibrate (option C) to reduce cardiovascular risk. This recommendation assumes the patient has moderate hypertriglyceridemia (likely 200-499 mg/dL based on "mildly elevated" description) with well-controlled LDL-C on the current statin regimen.

Rationale for Fenofibrate Selection

The primary therapeutic goal is addressing residual cardiovascular risk from elevated triglycerides while maintaining LDL-C control. 1 When LDL-C is already well-controlled on statin therapy but triglycerides remain elevated in the moderate range (200-499 mg/dL), fenofibrate provides 30-50% triglyceride reduction and helps achieve the secondary target of non-HDL-C <130 mg/dL. 2, 1

The 2021 ACC Expert Consensus specifically addresses this clinical scenario, recommending fibrates for patients with persistent hypertriglyceridemia despite statin therapy. 3 The 2012 European guidelines support fenofibrate as the preferred fibrate when combining with statins due to its superior safety profile compared to gemfibrozil. 3

Why NOT Omega-3 Fatty Acids (Option A)

Omega-3 fatty acids (specifically icosapent ethyl) are indicated only for specific high-risk populations: patients with triglycerides ≥150 mg/dL who have either established cardiovascular disease or diabetes with ≥2 additional cardiovascular risk factors, and who are already on maximally tolerated statin therapy with controlled LDL-C. 3, 2

Without knowing this patient's cardiovascular disease status or diabetes status, omega-3 cannot be recommended as first-line. The 2024 Diabetes Care guidelines note that omega-3 carboxylic acid formulations (EPA+DHA) did not reduce cardiovascular events in the STRENGTH trial, and only icosapent ethyl (pure EPA) showed benefit in the specific REDUCE-IT population. 3

Why NOT Evolocumab (Option B)

Evolocumab is a PCSK9 inhibitor indicated for LDL-C lowering, not triglyceride management. 4 The 2018 ACC/AHA guidelines recommend PCSK9 inhibitors for patients who require additional LDL-C lowering beyond maximally tolerated statin therapy—typically when LDL-C remains ≥70 mg/dL despite high-intensity statins in very high-risk patients. 3

This patient has "normal cholesterol" and the clinical question centers on triglyceride management, making evolocumab inappropriate. 4 PCSK9 inhibitors provide only modest triglyceride reduction (15-20%) compared to fenofibrate's 30-50% reduction. 3, 2

Treatment Algorithm and Monitoring

Initiate fenofibrate 54-160 mg daily (dose adjusted for renal function) while continuing the current high-dose statin. 1, 5 Consider reducing statin intensity from high-dose to moderate-dose if the patient is on atorvastatin 80 mg or rosuvastatin 40 mg to minimize myopathy risk, provided LDL-C remains controlled. 1

Target goals:

• Triglycerides <200 mg/dL (ideally <150 mg/dL) 2
• Non-HDL-C <130 mg/dL 2, 1
• Maintain LDL-C at current controlled level 1

Monitoring requirements:

• Obtain baseline creatine kinase (CK) and liver function tests before initiating fenofibrate 1
• Recheck fasting lipid panel in 4-8 weeks 1
• Monitor liver enzymes and CK at 3 months, then every 6-12 months once stable 1
• Educate patient about muscle symptoms and instruct to report myalgia immediately 3

Critical Safety Considerations

The combination of high-dose statin plus fibrate increases myopathy risk. 3, 1 Fenofibrate has a significantly better safety profile than gemfibrozil when combined with statins because it does not inhibit statin glucuronidation. 3, 2 The risk of clinical myositis remains low but requires vigilant monitoring, particularly in patients >65 years or with renal disease. 3, 1

Dose fenofibrate based on renal function: Use 54 mg daily maximum if eGFR 30-59 mL/min/1.73 m², and fenofibrate is contraindicated if eGFR <30 mL/min/1.73 m². 2

Lifestyle Modifications (Concurrent with Pharmacotherapy)

Aggressively implement lifestyle changes alongside fenofibrate:

• Target 5-10% weight loss (produces 20% triglyceride reduction) 2, 5
• Restrict added sugars to <6% of total daily calories 2
• Limit total dietary fat to 30-35% of calories 2
• Restrict saturated fats to <7% of calories 2
• Eliminate or drastically reduce alcohol consumption 2
• Engage in ≥150 minutes/week of moderate-intensity aerobic activity 2

If Triglycerides Remain Elevated After 3 Months

If triglycerides remain >200 mg/dL after 3 months of fenofibrate plus optimized lifestyle modifications, then consider adding prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) if the patient meets criteria (established cardiovascular disease or diabetes with ≥2 additional risk factors). 1, 5 This sequential approach prioritizes the most effective triglyceride-lowering agent first while reserving omega-3 for refractory cases in appropriate populations.