What is the optimal lipid‑lowering treatment for an 86‑year‑old woman with cardiovascular disease, allergic to niacin, rosuvastatin (Crestor) and simvastatin (Zocor), and a lipid panel showing total cholesterol 243 mg/dL, LDL 161 mg/dL, HDL 39 mg/dL, and triglycerides 216 mg/dL?

Lipid Management in an 86-Year-Old Woman with Cardiovascular Disease and Multiple Statin Allergies

Initiate ezetimibe 10 mg daily immediately, then add bempedoic acid 180 mg daily after 4–6 weeks if LDL-C remains ≥70 mg/dL, and consider adding a PCSK9 inhibitor (alirocumab or inclisiran) if LDL-C stays ≥70 mg/dL despite dual therapy. This patient has established atherosclerotic cardiovascular disease, placing her in the very-high-risk category with an LDL-C goal of <55 mg/dL and ≥50% reduction from baseline. 1, 2

Risk Stratification and Treatment Goals

This 86-year-old woman with established cardiovascular disease falls into the very-high-risk category, mandating aggressive LDL-C lowering to prevent recurrent cardiovascular events. 1 Her current LDL-C of 161 mg/dL is nearly three times the recommended target of <55 mg/dL for very-high-risk patients. 1, 2 The 2024 International Lipid Expert Panel emphasizes that only ≈22% of very-high-risk secondary-prevention patients in Europe achieve LDL-C <55 mg/dL, and approximately 20% experience recurrent cardiovascular events within 24 months, underscoring the urgency of intensive lipid lowering. 1, 2

Her triglycerides of 216 mg/dL and HDL-C of 39 mg/dL represent an atherogenic dyslipidemia pattern that compounds her cardiovascular risk. 3 The non-HDL-C (calculated as 243 – 39 = 204 mg/dL) exceeds the secondary target of <85 mg/dL for very-high-risk patients. 2, 4

Confirmed Statin Intolerance

The patient's documented allergies to simvastatin (Zocor) and rosuvastatin (Crestor) constitute true statin intolerance, as she has failed at least two different statins. 2, 4 True complete statin intolerance occurs in <3% of patients, but when confirmed, non-statin lipid-lowering therapy becomes mandatory. 2, 4 The 2025 ACC/AHA guidelines issue a Class I recommendation (Level B-R) for non-statin lipid-lowering therapy in statin-intolerant patients. 2

First-Line Therapy: Ezetimibe

Start ezetimibe 10 mg once daily immediately. Ezetimibe is the preferred initial non-statin agent, providing a 15–20% LDL-C reduction with minimal side effects. 2, 4 The American College of Cardiology and European Society of Cardiology give ezetimibe a Class I recommendation as second-line therapy in statin-intolerant patients, based on the IMPROVE-IT trial demonstrating clear cardiovascular benefit and its established long-term safety profile. 2, 4 Ezetimibe blocks intestinal cholesterol absorption via the NPC1L1 protein and can be taken with or without food. 2, 4

Expected outcome: Ezetimibe should lower her LDL-C from 161 mg/dL to approximately 129–137 mg/dL (15–20% reduction), which remains well above the target of <55 mg/dL. 2, 4

Second-Line Add-On: Bempedoic Acid

Add bempedoic acid 180 mg daily after 4–6 weeks if LDL-C remains ≥70 mg/dL. The combination of ezetimibe plus bempedoic acid achieves an overall LDL-C reduction of ≈35–38%, which would bring her LDL-C from 161 mg/dL to approximately 100–105 mg/dL—still above target but substantially improved. 2, 4

Bempedoic acid is the preferred non-statin option with outcomes data. The CLEAR Outcomes trial demonstrated a 13% reduction in major adverse cardiovascular events in statin-intolerant patients (median 3.4-year follow-up, HR 0.87; 95% CI 0.79–0.96; p=0.0037). 2, 4 Bempedoic acid acts upstream of HMG-CoA reductase by inhibiting hepatic ATP-citrate lyase but is inactive in skeletal muscle, thereby avoiding muscle-related adverse effects that plague statins. 2, 4

Critical monitoring for bempedoic acid:

• Monitor serum uric acid at baseline and periodically; bempedoic acid raises uric acid by an average of 0.8 mg/dL, and gout occurred in 1.5% of patients versus 0.4% with placebo. 2
• Check liver function tests (ALT/AST) at baseline and periodically. 2, 4
• Tendon rupture was reported in 0.5% of bempedoic-acid recipients versus 0% with placebo; educate the patient to report tendon pain promptly. 2

Third-Line Therapy: PCSK9 Inhibitors

If LDL-C remains ≥70 mg/dL despite ezetimibe plus bempedoic acid, add a PCSK9 inhibitor (alirocumab or inclisiran). PCSK9 inhibitors lower LDL-C by approximately 50–60% and are well-tolerated in statin-intolerant patients with minimal muscle-related adverse effects. 2, 4 The ODYSSEY ALTERNATIVE trial demonstrated that alirocumab reduced LDL-C by 54.8% in statin-intolerant patients with fewer skeletal-muscle adverse events (32.5%) compared with ezetimibe (41.1%) or atorvastatin rechallenge (46%). 2, 4

Alirocumab is administered as 75–150 mg subcutaneously every 2 weeks. 2 Inclisiran offers the convenience of twice-yearly dosing (day 1, day 90, then every 6 months) and provides a sustained ≈45% LDL-C reduction. 2, 4 Given the patient's documented allergy to rosuvastatin (Crestor), verify that the allergy is drug-specific rather than a class effect before assuming all PCSK9 inhibitors are contraindicated. 2

The 2024 International Lipid Expert Panel gives a Class I recommendation to add a PCSK9 inhibitor in very-high-risk patients who do not achieve LDL-C targets despite maximally tolerated therapy. 1, 2

Management of Hypertriglyceridemia and Low HDL-C

Her triglycerides of 216 mg/dL fall into the moderate hypertriglyceridemia range (200–499 mg/dL), which is associated with increased cardiovascular risk but is below the 500 mg/dL threshold that mandates fibrate therapy for pancreatitis prevention. 3 Her HDL-C of 39 mg/dL is below the target of >40 mg/dL for women. 2

Lifestyle interventions are foundational:

• Weight loss: A 5–10% reduction in body weight yields an approximate 20% decrease in triglycerides—the most effective single lifestyle measure. 3
• Dietary modifications: Restrict added sugars to <6% of total daily calories (≈30 g on a 2,000-kcal diet), limit total dietary fat to 30–35% of calories, restrict saturated fat to <7% of calories and replace with monounsaturated or polyunsaturated fats, eliminate trans fats completely, and increase soluble fiber to >10 g/day. 3
• Physical activity: ≥150 minutes/week of moderate-intensity aerobic exercise (or 75 minutes/week vigorous) reduces triglycerides by ≈11%. 3
• Alcohol: Limit or avoid alcohol; even modest intake (≈1 oz daily) raises triglycerides by 5–10%. 3

Pharmacologic therapy for triglycerides is deferred initially. The priority is achieving the LDL-C goal of <55 mg/dL with ezetimibe, bempedoic acid, and potentially a PCSK9 inhibitor. 1, 2 Ezetimibe and bempedoic acid will also modestly lower triglycerides (ezetimibe by ≈8%, bempedoic acid by 15–25%). 2, 4 If triglycerides remain >200 mg/dL after 3 months of optimized lipid therapy and lifestyle modifications, consider adding icosapent ethyl 2 g twice daily if she has established cardiovascular disease (which she does). The REDUCE-IT trial demonstrated a 25% reduction in major adverse cardiovascular events with icosapent ethyl in patients with triglycerides ≥150 mg/dL on statin therapy. 2, 3

Do not add fenofibrate at this stage. Fenofibrate is reserved for triglycerides ≥500 mg/dL to prevent acute pancreatitis. 3 The ACCORD trial demonstrated no cardiovascular event reduction when fenofibrate was added to simvastatin in diabetics, limiting its role to triglyceride lowering rather than cardiovascular risk reduction. 2, 3

Monitoring Strategy

• Reassess fasting lipid panel 4–6 weeks after initiating ezetimibe to determine whether bempedoic acid should be added. 2, 4
• Recheck lipids 4–6 weeks after adding bempedoic acid to assess whether a PCSK9 inhibitor is needed. 2, 4
• Monitor for muscle symptoms with baseline and follow-up creatine kinase levels, although the risk is low with ezetimibe and bempedoic acid. 2, 4
• Check liver function tests at baseline and periodically when using bempedoic acid. 2, 4
• Monitor serum uric acid and watch for gout when using bempedoic acid. 2
• Reassess triglycerides and HDL-C after 3 months of optimized therapy to determine whether icosapent ethyl is needed. 2, 3

Treatment Goals

• Primary goal: LDL-C <55 mg/dL with ≥50% reduction from baseline (from 161 mg/dL). 1, 2
• Secondary goal: Non-HDL-C <85 mg/dL (currently 204 mg/dL). 2
• Tertiary goal: Triglycerides <200 mg/dL (ideally <150 mg/dL; currently 216 mg/dL). 3
• Quaternary goal: HDL-C >40 mg/dL for women (currently 39 mg/dL). 2

Critical Pitfalls to Avoid

• Do not delay non-statin therapy while attempting lifestyle changes alone in this very-high-risk patient with established cardiovascular disease; pharmacotherapy and lifestyle optimization should occur concurrently. 2, 4
• Do not prescribe niacin. The patient has a documented allergy to niacin (listed as "Crystal," likely referring to crystalline niacin). Moreover, the AIM-HIGH trial showed no cardiovascular benefit from adding niacin to statin therapy, with increased risk of new-onset diabetes and gastrointestinal disturbances. 2, 4, 5
• Do not overlook secondary causes of dyslipidemia (e.g., hypothyroidism, uncontrolled diabetes, medications that raise lipids). Correcting these can improve lipid levels by 20–50% independent of lipid-lowering drugs. 2, 3
• Do not assume all PCSK9 inhibitors are contraindicated based on the rosuvastatin allergy; alirocumab and inclisiran have different molecular structures and may be tolerated. 2
• Do not use over-the-counter fish oil supplements for cardiovascular benefit; only prescription icosapent ethyl has proven outcome data. 2, 3

Age-Specific Considerations

At 86 years old, this patient's life expectancy and functional status should inform treatment intensity, but her established cardiovascular disease justifies aggressive lipid lowering to prevent recurrent events. 4 The 2012 American Geriatrics Society guideline notes that statins remain indicated for secondary prevention in older adults, and the same principle applies to non-statin therapies in statin-intolerant patients. 4 Simplifying the medication regimen to once-daily dosing (ezetimibe, bempedoic acid) improves adherence in older patients. 4

Summary Algorithm

1. Initiate ezetimibe 10 mg daily immediately (expected 15–20% LDL-C reduction). 2, 4
2. Reassess lipids at 4–6 weeks. If LDL-C ≥70 mg/dL, add bempedoic acid 180 mg daily (combined expected 35–38% LDL-C reduction). 2, 4
3. Reassess lipids at 4–6 weeks after adding bempedoic acid. If LDL-C ≥70 mg/dL, add a PCSK9 inhibitor (alirocumab or inclisiran; expected additional 50–60% LDL-C reduction). 2, 4
4. Implement intensive lifestyle modifications for triglycerides and HDL-C (weight loss, dietary changes, physical activity, alcohol restriction). 3
5. Reassess triglycerides after 3 months. If triglycerides remain >200 mg/dL despite optimized lipid therapy and lifestyle changes, add icosapent ethyl 2 g twice daily. 2, 3
6. Monitor for adverse effects: uric acid and gout (bempedoic acid), liver function tests (bempedoic acid), atrial fibrillation (icosapent ethyl if added). 2, 3