In a 57-year-old woman taking rosuvastatin 10 mg daily with total cholesterol 218 mg/dL, triglycerides 149 mg/dL, HDL‑cholesterol 61 mg/dL and LDL‑cholesterol 131 mg/dL, what is the appropriate next step in lipid‑lowering management?

Management of Elevated LDL-C on Current Rosuvastatin Therapy

Add ezetimibe 10 mg daily to the current rosuvastatin 10 mg regimen immediately to achieve the LDL-C goal of <100 mg/dL (ideally <70 mg/dL for a 57-year-old woman who likely has cardiovascular risk factors). 1, 2

Current Lipid Status Analysis

Your patient's lipid panel reveals:

• LDL-C 131 mg/dL – above the target of <100 mg/dL for most adults and well above <70 mg/dL for high-risk patients 1, 3
• HDL-C 61 mg/dL – protective level (>50 mg/dL for women) 3
• Triglycerides 149 mg/dL – normal range (<150 mg/dL) 3
• Total cholesterol 218 mg/dL – borderline high 3

The patient is already on rosuvastatin 10 mg, which typically provides 45-50% LDL-C reduction 1, 4, 5. The fact that LDL-C remains at 131 mg/dL suggests either suboptimal baseline levels or the need for intensified therapy.

Treatment Algorithm

Step 1: Add Ezetimibe to Current Statin

The combination of rosuvastatin 10 mg plus ezetimibe 10 mg is the recommended next step rather than uptitrating rosuvastatin alone. 1, 2

Rationale:

• Ezetimibe added to rosuvastatin 10 mg provides an additional 15-25% LDL-C reduction beyond statin monotherapy 1, 2
• This combination is more effective and better tolerated than doubling the rosuvastatin dose to 20 mg 1
• The I-ROSETTE trial specifically demonstrated that ezetimibe 10 mg/rosuvastatin 10 mg achieved >50% LDL-C reduction from baseline with comparable safety to rosuvastatin monotherapy 1
• Fixed-dose combinations reduce pill burden and improve adherence 1

Expected outcome: LDL-C should decrease from 131 mg/dL to approximately 85-100 mg/dL (an additional 20-30 mg/dL reduction) 1, 2

Step 2: Reassess in 4-6 Weeks

• Obtain fasting lipid panel 4-6 weeks after adding ezetimibe 1, 3
• Target: LDL-C <100 mg/dL (or <70 mg/dL if she has diabetes, established ASCVD, or other very high-risk features) 1, 3

Step 3: If LDL-C Remains ≥70-100 mg/dL Despite Combination Therapy

Consider adding a PCSK9 inhibitor (evolocumab 140 mg subcutaneously every 2 weeks or alirocumab 75-150 mg every 2 weeks) if:

• LDL-C remains ≥70 mg/dL in very high-risk patients despite maximally tolerated statin plus ezetimibe 1, 2
• PCSK9 inhibitors provide an additional 50-60% LDL-C reduction when added to statin therapy 1, 2

Why NOT Uptitrate Rosuvastatin First?

Doubling the statin dose (rosuvastatin 10 mg → 20 mg) provides only an additional 6-7% LDL-C reduction, whereas adding ezetimibe provides 15-25% additional reduction. 1, 2

The ACTE trial directly compared these strategies and found that ezetimibe 10 mg added to stable rosuvastatin 5-10 mg produced greater LDL-C improvements and better goal achievement than uptitrating rosuvastatin alone. 1

Common pitfall: Clinicians often unnecessarily uptitrate statin doses when adding ezetimibe is more effective and avoids dose-dependent statin side effects (myalgia, elevated liver enzymes). 1

Safety Monitoring

• Baseline (before adding ezetimibe): No additional labs required if recent hepatic transaminases are normal 1, 6
• Hepatic monitoring: Check ALT/AST if clinically indicated; routine monitoring is not required during stable combination therapy 1
• Muscle symptoms: Assess at each visit; obtain creatine kinase only if symptoms develop 1
• Adverse events: The combination of rosuvastatin plus ezetimibe has a safety profile comparable to statin monotherapy 1, 2

Concurrent Lifestyle Optimization

While adding ezetimibe, reinforce:

• Saturated fat <7% of total calories (eliminate cheese, whole milk, fatty red meat) 3, 7
• Dietary cholesterol <200 mg/day 3, 7
• Plant stanols/sterols 2 g/day (additional 6-15% LDL-C reduction) 3, 7
• Soluble fiber 10-25 g/day from oats, beans, vegetables 3, 7
• Moderate-intensity aerobic exercise ≥30 minutes most days 3, 7

Risk Stratification Considerations

At age 57, this woman likely qualifies as high-risk or very high-risk if she has:

• Diabetes mellitus (target LDL-C <70 mg/dL, ideally <55 mg/dL) 1
• Established ASCVD (prior MI, stroke, PAD) (target LDL-C <55 mg/dL with ≥50% reduction) 1
• Multiple cardiovascular risk factors with 10-year ASCVD risk ≥7.5% (target LDL-C <100 mg/dL, consider <70 mg/dL) 2, 3

If she experienced a cardiovascular event within the past 2 years while on statin therapy, consider an even more aggressive target of LDL-C <40 mg/dL (1.0 mmol/L). 1

Key Clinical Pearls

• Do not delay adding ezetimibe – the IMPROVE-IT trial demonstrated that high-risk patients derive the greatest cardiovascular benefit from early combination therapy 1, 2
• Ezetimibe has no significant drug interactions with rosuvastatin and can be taken at the same time 6
• If the patient is also taking bile acid sequestrants, administer ezetimibe ≥2 hours before or ≥4 hours after the sequestrant 6
• Annual lipid monitoring once LDL-C goals are achieved and stable 3, 7