A 52-year-old woman taking rosuvastatin (Crestor) 10 mg daily has total cholesterol 164 mg/dL, triglycerides 200 mg/dL, HDL‑cholesterol 30.8 mg/dL, and LDL‑cholesterol 106 mg/dL; how should her lipid management be adjusted?

Management of Suboptimal Lipid Control on Rosuvastatin 10 mg

Add ezetimibe 10 mg daily to the current rosuvastatin 10 mg regimen immediately, and address the critically low HDL-cholesterol with intensive lifestyle modification. This 52-year-old woman has achieved partial LDL-C control (106 mg/dL) but demonstrates two high-risk features: severely low HDL-C (30.8 mg/dL, target >50 mg/dL for women) and elevated triglycerides (200 mg/dL, target <150 mg/dL), creating an atherogenic dyslipidemia pattern that requires combination pharmacotherapy 1, 2.

Current Lipid Status and Risk Assessment

• LDL-C of 106 mg/dL exceeds the recommended target of <100 mg/dL for women with cardiovascular risk factors, and ideally <70 mg/dL if diabetes or established atherosclerotic disease is present 3, 1.
• HDL-C of 30.8 mg/dL is critically low (goal >50 mg/dL for women), representing a major independent cardiovascular risk factor 3, 2.
• Triglycerides of 200 mg/dL are elevated (goal <150 mg/dL), contributing to residual cardiovascular risk even when LDL-C approaches target 3, 1.
• Non-HDL-C is 133 mg/dL (calculated as 164 – 30.8), which exceeds the goal of <130 mg/dL for intermediate-risk patients 3, 2.
• The total cholesterol/HDL-C ratio is 5.3 (164 ÷ 30.8), well above the optimal ratio of <4.5, indicating elevated cardiovascular risk 2.

Primary Recommendation: Add Ezetimibe

• Add ezetimibe 10 mg once daily to the current rosuvastatin 10 mg regimen rather than uptitrating the rosuvastatin dose 1, 2.
• Ezetimibe provides an additional 15–25% LDL-C reduction beyond statin monotherapy, which should lower LDL-C from 106 mg/dL to approximately 80–90 mg/dL 3, 1, 2.
• Combining rosuvastatin 10 mg + ezetimibe 10 mg is more effective and better tolerated than doubling rosuvastatin to 20 mg, which yields only a 6–7% additional LDL-C reduction 1, 2.
• The combination achieves >50% LDL-C reduction from baseline with a safety profile comparable to rosuvastatin alone 1, 2.
• Fixed-dose combinations improve adherence by reducing pill burden 1.

Addressing the Low HDL-C and Elevated Triglycerides

• Intensive therapeutic lifestyle changes are the first-line intervention for low HDL-C and moderate hypertriglyceridemia 3.
• Limit saturated fat to <7% of total calories (reduce cheese, whole milk, fatty red meat) and keep dietary cholesterol <200 mg/day 3, 1.
• Consume plant stanols/sterols 2 g/day, which provide an additional 6–15% LDL-C reduction 1.
• Aim for soluble fiber 10–25 g/day (oats, beans, vegetables) 1.
• Perform moderate-intensity aerobic exercise ≥30 minutes most days of the week 3, 2.
• Weight reduction targeting BMI 18.5–24.9 kg/m² and waist circumference <35 inches for women 2.
• Limit alcohol intake to ≤1 drink/day for women, as excessive alcohol raises triglycerides 3.

Consider Fenofibrate if Lipids Remain Suboptimal

• If triglycerides remain ≥200 mg/dL and HDL-C remains <40 mg/dL after 8–12 weeks on rosuvastatin + ezetimibe with lifestyle optimization, add fenofibrate 54–160 mg once daily 4.
• Fenofibrate lowers triglycerides by 30–50% and raises HDL-C by 10–20%, addressing the non-LDL components of atherogenic dyslipidemia 4.
• Fenofibrate can be safely combined with rosuvastatin with minimal myopathy risk (<2%), unlike gemfibrozil which markedly increases this risk 4.
• Separate fenofibrate and rosuvastatin dosing by at least 2 hours (e.g., fenofibrate in the morning, rosuvastatin in the evening) to further reduce myopathy risk 4.

Monitoring and Follow-Up

• Re-measure fasting lipid panel 4–6 weeks after adding ezetimibe 3, 1, 2.
• Target lipid goals:
  • LDL-C <100 mg/dL (or <70 mg/dL if diabetes or high cardiovascular risk) 3, 1
  • Non-HDL-C <130 mg/dL (or <100 mg/dL if high risk) 3, 2
  • Triglycerides <150 mg/dL 3, 1, 4
  • HDL-C >50 mg/dL for women 3, 2, 4
• No additional baseline labs are required before adding ezetimibe if recent hepatic transaminases (ALT/AST) are normal 3, 1.
• Monitor ALT/AST at 8–12 weeks after adding ezetimibe; routine hepatic monitoring thereafter is unnecessary during stable combination therapy unless clinically indicated 3, 1.
• Assess muscle symptoms at each visit; obtain creatine kinase (CK) only if symptoms develop 3, 1.
• If CK >10× upper limit of normal (ULN): discontinue both medications and monitor renal function 3.
• If CK 4–10× ULN with symptoms: discontinue statin and ezetimibe, monitor CK every 2 weeks 3.
• If CK <4× ULN with symptoms: continue therapy while monitoring CK 3.
• Once lipid goals are achieved and stable, perform annual lipid monitoring unless adherence issues or clinical changes dictate more frequent testing 3, 1.

Escalation Strategy if Goals Not Met

• If LDL-C remains ≥70–100 mg/dL despite maximally tolerated rosuvastatin + ezetimibe, consider adding a PCSK9 inhibitor (evolocumab 140 mg subcutaneously every 2 weeks or alirocumab 75–150 mg subcutaneously every 2 weeks) 1, 4.
• PCSK9 inhibitors provide an additional 50–60% LDL-C reduction when combined with statin + ezetimibe therapy 1.

Critical Pitfalls to Avoid

• Do not delay ezetimibe addition while attempting further rosuvastatin dose uptitration; each month of delay increases cardiovascular risk, and dose doubling yields minimal additional LDL-C reduction 1, 2.
• Do not add gemfibrozil to rosuvastatin, as it markedly increases myopathy risk; use fenofibrate instead if fibrate therapy is needed 4.
• Do not prioritize HDL-C or triglycerides as primary treatment goals; LDL-C reduction remains the primary target for cardiovascular risk mitigation 3, 4.
• Do not discontinue rosuvastatin when adding ezetimibe or fenofibrate; statins remain the only lipid-lowering class with robust mortality benefit in cardiovascular outcome trials 4.
• Do not initiate niacin, as it has not demonstrated cardiovascular benefit when added to statin therapy and is associated with increased diabetes risk and gastrointestinal side effects 4.

Patient Education and Adherence

• Before prescribing ezetimibe, engage in a shared decision-making discussion about the potential for cardiovascular risk reduction, adverse effects, drug-drug interactions, and patient preferences 3.
• Use multiple interventions to promote adherence: telephone reminders, calendar reminders, simplification to once-daily dosing, and pharmacist-led interventions 3.
• Encourage the patient to state what was heard, ask questions, express values and preferences, and state ability and willingness to adhere to lifestyle changes and medications 3.
• Discuss out-of-pocket costs during the clinician-patient discussion 3.