How should I manage a 74-year-old woman on fenofibrate 150 mg daily and pravastatin 80 mg daily with low-density lipoprotein 99 mg/dL, high-density lipoprotein 49 mg/dL, and triglycerides 258 mg/dL?

Management of a 74-Year-Old Woman on Fenofibrate 150 mg and Pravastatin 80 mg with LDL 99 mg/dL, HDL 49 mg/dL, and Triglycerides 258 mg/dL

Continue both fenofibrate 150 mg and pravastatin 80 mg, as this combination is safe and effective for mixed dyslipidemia, and consider adding icosapent ethyl 2 g twice daily if she has established cardiovascular disease or diabetes with additional risk factors to further reduce triglycerides and cardiovascular events. 1

Current Lipid Status and Treatment Goals

Your patient has moderate hypertriglyceridemia (200–499 mg/dL) with borderline LDL-C and low HDL-C, representing classic mixed dyslipidemia that warrants continued combination therapy. 2 The current regimen is appropriate because:

• LDL-C of 99 mg/dL is near but not quite at goal (<100 mg/dL for high-risk patients, <70 mg/dL for very high-risk), suggesting the pravastatin 80 mg is providing benefit but may need optimization. 3
• Triglycerides of 258 mg/dL remain elevated despite fenofibrate, indicating persistent cardiovascular risk from atherogenic remnant particles. 2
• HDL-C of 49 mg/dL is below the optimal target of >50 mg/dL for women, another residual risk factor. 3
• Non-HDL-C (calculated as total cholesterol minus HDL-C) should be <130 mg/dL; with her current lipids, this equals approximately 148 mg/dL (99 LDL + 258/5 VLDL estimate), which is above goal. 3, 2

Safety of Fenofibrate-Statin Combination in This Patient

The combination of fenofibrate with pravastatin is remarkably safe and appropriate for long-term use in a 74-year-old woman. 1 Here's why:

• Fenofibrate is the preferred fibrate when combining with any statin because it has approximately 15 times lower risk of rhabdomyolysis compared to gemfibrozil (0.58 vs 8.6 cases per million prescriptions). 1
• Pravastatin is one of the safest statins to combine with fenofibrate because it is not metabolized by CYP450 enzymes, minimizing drug interactions. 1
• The FIELD study reported zero cases of rhabdomyolysis among approximately 1,000 patients on statin-fenofibrate combination, demonstrating excellent safety. 1
• The ACCORD trial showed no statistically significant differences in myositis, rhabdomyolysis, or hepatic transaminase elevations with simvastatin-fenofibrate versus simvastatin alone. 1

However, at age 74, she requires closer monitoring because advanced age is a risk factor for statin-fibrate associated myopathy, particularly in older, thin, or frail women. 1 Monitor muscle symptoms and creatine kinase at baseline, 6–12 weeks after any dose change, and then at each follow-up visit. 1

Optimizing the Current Regimen

Option 1: Add Icosapent Ethyl (Strongest Evidence for Cardiovascular Outcomes)

If your patient has established cardiovascular disease OR diabetes with ≥2 additional cardiovascular risk factors, add icosapent ethyl 2 g twice daily (total 4 g/day) to her current regimen. 1, 2 This is the only triglyceride-lowering therapy FDA-approved for cardiovascular risk reduction and demonstrated:

• 25% reduction in major adverse cardiovascular events in the REDUCE-IT trial (number needed to treat = 21). 1, 2
• Additional 20–50% triglyceride reduction when added to statin therapy. 2
• No increased myopathy risk when combined with statins, unlike fibrates. 1

Monitor for increased risk of atrial fibrillation (3.1% vs 2.1% with placebo), particularly important in a 74-year-old. 1, 2

Option 2: Continue Current Therapy with Lifestyle Intensification

If she does not meet criteria for icosapent ethyl, continue fenofibrate 150 mg and pravastatin 80 mg while aggressively optimizing lifestyle modifications for 3 months, then reassess. 2

Lifestyle modifications that can reduce triglycerides by 20–50%: 2

• Target 5–10% body weight reduction, which produces a 20% decrease in triglycerides (the single most effective intervention). 2
• Restrict added sugars to <6% of total daily calories (approximately 30 g on a 2,000-calorie diet), as sugar directly increases hepatic triglyceride production. 2
• Limit total dietary fat to 30–35% of total calories for moderate hypertriglyceridemia. 2
• Restrict saturated fats to <7% of total energy intake, replacing with monounsaturated or polyunsaturated fats. 2
• Consume ≥2 servings per week of fatty fish (salmon, trout, sardines) rich in omega-3 fatty acids. 2
• Engage in ≥150 minutes/week of moderate-intensity aerobic activity, which reduces triglycerides by approximately 11%. 2
• Limit or completely avoid alcohol, as even 1 ounce daily increases triglycerides by 5–10%. 2

Option 3: Consider Switching Pravastatin to a More Potent Statin

Pravastatin 80 mg is the maximum dose but provides less LDL-C reduction than high-intensity statins. 1 If LDL-C remains above goal after 3 months, consider switching to:

• Atorvastatin 40 mg (provides ≥50% LDL-C reduction, classified as high-intensity). 1
• Rosuvastatin 20 mg (provides ≥50% LDL-C reduction, classified as high-intensity). 1

When combining with fenofibrate, use lower statin doses to minimize myopathy risk, particularly in patients >65 years. 1 If switching, start with atorvastatin 20 mg or rosuvastatin 10 mg and titrate based on response and tolerability. 1

Monitoring Strategy

Reassess fasting lipid panel in 4–8 weeks after any medication adjustment or lifestyle intervention. 2 Target goals:

• Primary goal: Reduce triglycerides to <200 mg/dL (ideally <150 mg/dL) to reduce cardiovascular risk. 2
• Secondary goal: Achieve non-HDL-C <130 mg/dL. 2
• Tertiary goal: Reach LDL-C <100 mg/dL (or <70 mg/dL for very high-risk patients). 2

Monitor for myopathy risk with baseline and follow-up creatine kinase levels, especially given her age and combination therapy. 1, 2

Check renal function (creatinine, eGFR) within 3 months after fenofibrate initiation and every 6 months thereafter, as fenofibrate is substantially excreted by the kidney. 4 If eGFR persistently decreases to <30 mL/min/1.73 m², fenofibrate must be discontinued immediately. 4

Monitor liver function tests (ALT, AST) at baseline and periodically during combination therapy. 4

Critical Pitfalls to Avoid

• Do not discontinue fenofibrate simply because triglycerides are not yet at goal; 258 mg/dL represents a 30–50% reduction from baseline if she started with triglycerides around 400–500 mg/dL. 1
• Do not switch to gemfibrozil instead of fenofibrate—gemfibrozil has significantly higher myopathy risk when combined with statins and should be avoided. 1
• Do not delay adding icosapent ethyl if she meets criteria (established ASCVD or diabetes with ≥2 risk factors), as this is the only add-on therapy with proven cardiovascular outcomes benefit. 1, 2
• Do not overlook secondary causes of persistent hypertriglyceridemia: uncontrolled diabetes (check HbA1c), hypothyroidism (check TSH), excessive alcohol intake, or medications that raise triglycerides (thiazides, beta-blockers, estrogen, corticosteroids). 2
• Do not use over-the-counter fish oil supplements expecting cardiovascular benefit—only prescription icosapent ethyl has proven efficacy. 2

Evidence Limitations and Nuances

The combination of statin plus fibrate has NOT been shown to improve cardiovascular outcomes compared to statin monotherapy in large trials. 1 The ACCORD trial demonstrated no reduction in fatal cardiovascular events, nonfatal MI, or nonfatal stroke with fenofibrate plus simvastatin compared to simvastatin alone in type 2 diabetes. 1 However, this does not mean the combination is inappropriate—it addresses residual dyslipidemia and may benefit specific subgroups (e.g., those with triglycerides ≥204 mg/dL and HDL-C ≥40 mg/dL). 3

In contrast, icosapent ethyl added to statin therapy has proven cardiovascular benefit, making it the preferred add-on agent if your patient meets criteria. 1, 2