Is fenofibrate (fibric acid derivative) suitable for a patient with low high-density lipoprotein (HDL) and mildly elevated triglycerides?

Fenofibrate is NOT Recommended for Your Lipid Profile

Fenofibrate should not be initiated in a patient with HDL-C of 19 mg/dL and triglycerides of 120 mg/dL, as the triglyceride level does not meet guideline thresholds for fibrate therapy and there is no evidence that adding fenofibrate to treat isolated low HDL-C reduces cardiovascular events. 1, 2

Why Fenofibrate is Inappropriate Here

Triglyceride Threshold Not Met

• Guideline-based thresholds establish that fenofibrate should only be considered when triglycerides are ≥200 mg/dL after optimizing LDL-C lowering therapy 2
• For triglycerides 200-499 mg/dL, fibrates may be considered as adjunctive therapy with a non-HDL-C target of <130 mg/dL 1, 2
• Fenofibrate is specifically recommended before LDL-lowering therapy only when triglycerides are ≥500 mg/dL to prevent pancreatitis 1, 2, 3
• Your patient's triglyceride level of 120 mg/dL is well below any threshold where fenofibrate has demonstrated benefit 2

No Evidence for Treating Isolated Low HDL-C

• The AIM-HIGH trial definitively demonstrated futility of adding niacin (another HDL-raising agent) in patients with low HDL-C when LDL-C was already at goal (40-80 mg/dL), despite achieving additional increases in HDL-C and reductions in triglycerides 1
• The ACCORD trial showed no cardiovascular benefit from adding fenofibrate to statin therapy in diabetic patients, even in post-hoc subgroup analysis of those with high triglycerides and low HDL-C (which was considered hypothesis-generating only and requires further testing) 1
• The independent effect of raising HDL-C on cardiovascular morbidity and mortality has not been established 3

What You Should Do Instead

Optimize Statin Therapy First

• Ensure the patient is on appropriate evidence-based statin intensity based on their ASCVD risk category (secondary prevention, diabetes, LDL-C ≥190 mg/dL, or primary prevention with elevated 10-year risk) 1, 2
• High-intensity statin therapy has the strongest evidence for reducing ASCVD events and should be maximized before considering any nonstatin therapy 1

Implement Aggressive Lifestyle Modifications

• Dietary changes: reduce saturated fat to <7% of total calories, cholesterol to <200 mg/day, and trans fat to <1% of calories 1, 2
• Weight loss of 5-10% can improve HDL-C levels 4
• Increase physical activity to at least 150 minutes per week of moderate-intensity exercise 4
• Eliminate or significantly limit alcohol consumption 4

Evaluate for Secondary Causes of Low HDL-C

• Screen for diabetes mellitus, hypothyroidism, chronic liver or kidney disease, and medications that lower HDL-C (beta-blockers, thiazides, anabolic steroids) 2
• Optimize glycemic control in diabetic patients 2

Critical Pitfalls to Avoid

Do not add nonstatin therapy simply to achieve arbitrary lipid targets when evidence-based statin therapy is not optimized 1. The 2013 ACC/AHA guidelines explicitly moved away from treat-to-target approaches because they can result in:

• Undertreatment with evidence-based statin therapy 1
• Overtreatment with nonstatin drugs that have not been shown to reduce ASCVD events in randomized controlled trials 1

If fenofibrate were inappropriately added with a statin, this combination increases the risk of myopathy and rhabdomyolysis, particularly in patients with chronic kidney disease 1. Fenofibrate is contraindicated when eGFR <30 mL/min/1.73m² 1.