In a 74-year-old woman with hypertriglyceridemia (triglycerides 354 mg/dL), which is the safer and more effective treatment: fenofibrate or ezetimibe (Zetia)?

Treatment Recommendation for 74-Year-Old Woman with Triglycerides 354 mg/dL

Neither fenofibrate nor ezetimibe (Zetia) is the optimal first-line choice for this patient—a statin should be initiated first, as statins are the only lipid-lowering agents proven to reduce cardiovascular morbidity and mortality in this population. 1

Primary Treatment Approach

Statin therapy is the foundation of treatment for this 74-year-old woman, regardless of her triglyceride level of 354 mg/dL. 1, 2 The 2013 ACC/AHA guidelines establish that statins provide proven cardiovascular risk reduction, while non-statin therapies (including both fenofibrate and ezetimibe) have not demonstrated consistent mortality or morbidity benefits when used as monotherapy. 1

Initial Statin Recommendation

• Start with moderate-intensity statin therapy (such as atorvastatin 10-20 mg daily) given her age and the need to assess tolerability in elderly patients. 2
• Elderly patients aged 65-80 years tolerate statin therapy well with significant absolute risk reduction. 2
• Obtain baseline lipid panel, liver function tests, creatine kinase, fasting glucose, and creatinine before initiating therapy. 2
• Recheck lipid panel at 4-12 weeks to assess response and adherence. 2

If Adjunctive Therapy Is Needed After Statin Optimization

If triglycerides remain elevated (>200 mg/dL) despite maximally tolerated statin therapy, fenofibrate is the more appropriate choice over ezetimibe for this specific indication.

Why Fenofibrate Over Ezetimibe for Hypertriglyceridemia

Fenofibrate substantially reduces triglycerides (by 31-43%), while ezetimibe has minimal effect on triglycerides (only 5-10% reduction). 1, 3

• In adults with diabetes and triglycerides <450 mg/dL, fenofibrate modestly reduced LDL-C, minimally increased HDL-C, and substantially reduced triglycerides. 1
• Fenofibrate added to simvastatin moderately reduced triglycerides by 23 mg/dL (14%) in patients with baseline triglycerides. 1
• Ezetimibe's primary mechanism targets cholesterol absorption, not triglyceride metabolism, making it ineffective for hypertriglyceridemia. 4, 5

Fenofibrate Safety Considerations in Elderly Women

Critical safety monitoring is required given this patient's age and sex:

• Renal function must be evaluated before initiation, within 3 months, and every 6 months thereafter. 1
• Fenofibrate should not be used if eGFR <30 mL/min/1.73 m². 1
• If eGFR is 30-59 mL/min/1.73 m², dose should not exceed 54 mg/day. 1, 6
• Women with well-controlled diabetes had higher CVD event rates with fenofibrate-simvastatin compared to simvastatin alone—this is a critical consideration for elderly women. 1
• Fenofibrate was associated with higher rates of pancreatitis, pulmonary embolism, and increased creatinine levels (average 0.113-0.136 mg/dL increase). 1

Ezetimibe Safety Profile (If Chosen)

Ezetimibe has a more favorable safety profile in elderly patients:

• Common adverse effects include upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities. 4
• It is reasonable to obtain baseline hepatic transaminases before initiation and monitor as clinically indicated. 1
• Ezetimibe modestly increased risk for muscle symptoms requiring discontinuation (1.1% vs 0.6% with placebo). 1
• No increased risk of hemorrhagic stroke, cancer, or noncardiovascular mortality. 1, 4

Clinical Algorithm for This Patient

1. Start moderate-intensity statin (e.g., atorvastatin 10-20 mg daily) with baseline labs including renal function. 2
2. Implement intensive lifestyle modifications: Step II AHA diet, increased physical activity, weight reduction if applicable, and limit alcohol intake. 2, 6
3. Recheck lipid panel at 4-12 weeks: Assess triglyceride response to statin therapy. 2
4. If triglycerides remain >200 mg/dL despite statin optimization:
   • Verify renal function (eGFR must be >30 mL/min/1.73 m²). 1
   • Consider adding fenofibrate 54 mg daily (lower dose given age and need for renal monitoring). 6
   • Do NOT use gemfibrozil with statin due to increased rhabdomyolysis risk. 1
5. Monitor renal function closely: Check within 3 months of fenofibrate initiation, then every 6 months. 1
6. Discontinue fenofibrate if eGFR persistently drops to <30 mL/min/1.73 m². 1

Common Pitfalls to Avoid

• Do not use fenofibrate or ezetimibe as monotherapy without first attempting statin therapy—only statins have proven cardiovascular mortality benefit. 1
• Do not combine gemfibrozil with any statin due to significantly increased myopathy risk. 1
• Do not ignore renal function monitoring with fenofibrate—this is mandatory given age-related decline in renal function. 1, 6
• Do not assume ezetimibe will address hypertriglyceridemia—its effect on triglycerides is minimal (5-10% reduction). 1, 3
• Be cautious in elderly women with diabetes—fenofibrate may paradoxically increase CVD events in this specific subgroup. 1