What is the best course of action for a patient with hypercholesterolemia and hypertriglyceridemia who is currently on 40 mg of rosuvastatin?

Management of Persistent Hyperlipidemia on Maximum-Dose Rosuvastatin

Add ezetimibe 10 mg daily to your patient's current rosuvastatin 40 mg regimen immediately, as this combination will provide an additional 15-25% LDL-C reduction and is the recommended next step for patients with severely elevated cholesterol on maximum statin therapy. 1

Current Clinical Status

Your patient presents with:

• Total cholesterol: 241 mg/dL (severely elevated)
• Triglycerides: 318 mg/dL (significantly elevated, indicating mixed dyslipidemia)
• Already on rosuvastatin 40 mg (maximum high-intensity statin dose) 2

This represents inadequate lipid control despite maximum-intensity statin therapy, requiring immediate treatment intensification rather than continued monotherapy. 1

Recommended Treatment Algorithm

Step 1: Add Ezetimibe Immediately

• Start ezetimibe 10 mg daily in addition to continuing rosuvastatin 40 mg 1
• The ACC/AHA guidelines explicitly recommend adding ezetimibe when baseline LDL-C levels remain very high on maximum statin therapy, rather than sequential monotherapy trials 1
• This combination provides synergistic LDL-C reduction of 15-25% beyond statin alone 1
• Do not wait 4-6 weeks to intensify therapy - the International Lipid Expert Panel recommends immediate addition of ezetimibe in this clinical scenario 1

Step 2: Address Hypertriglyceridemia

Your patient's triglycerides of 318 mg/dL require specific attention:

• Rosuvastatin 40 mg already provides moderate triglyceride reduction (approximately 28-43% reduction in hypertriglyceridemic patients) 3
• Lifestyle modifications are essential: reduce saturated fat to <7% of calories, limit cholesterol to <200 mg/day, increase physical activity, achieve weight loss if overweight, and reduce alcohol consumption 4, 1
• At triglyceride levels between 200-400 mg/dL, the primary focus remains LDL-C reduction with statins and ezetimibe 4
• Above 400 mg/dL, fibrate therapy should be strongly considered to minimize pancreatitis risk 4

Step 3: Establish Target Goals

Based on cardiovascular risk stratification:

• If clinical ASCVD is present: Target LDL-C <55 mg/dL with ≥50% reduction from baseline 1
• If no ASCVD but major risk factors present: Target LDL-C <70 mg/dL 1
• For primary prevention with elevated risk: Target LDL-C <100 mg/dL 1

Step 4: Monitor and Further Intensify if Needed

• Recheck lipid panel in 4-6 weeks after adding ezetimibe 1
• Monitor for muscle symptoms and hepatic transaminases as recommended for statin therapy 1
• If LDL-C remains >70 mg/dL after 4-6 weeks on rosuvastatin 40 mg plus ezetimibe, add a PCSK9 inhibitor:
  • Evolocumab 140 mg subcutaneously every 2 weeks, OR
  • Alirocumab 75-150 mg subcutaneously every 2 weeks 1

Critical Considerations

Screen for Familial Hypercholesterolemia

Your patient may have heterozygous familial hypercholesterolemia (HeFH), which affects approximately 1 in 250 people and requires specialized management. 1 The Nature Reviews Cardiology recommends screening for HeFH in patients with LDL-C >190 mg/dL on maximum-dose statin therapy. 1

Why Not Switch Statins?

• Rosuvastatin 40 mg is already the most potent statin available (reduces LDL-C by 63%) 4, 3
• Switching to atorvastatin 80 mg would provide equivalent or slightly less LDL-C reduction 2
• The problem is inadequate response to monotherapy, not statin choice 1

Addressing Low HDL-C

While not specified in your question, patients with this lipid profile often have low HDL-C:

• Emphasize weight management and physical activity 1
• Advise smoking cessation if applicable 1
• Rosuvastatin produces significant HDL-C increases (up to 14% at higher doses) 5, 6

Common Pitfalls to Avoid

• Don't continue statin monotherapy indefinitely when lipid goals are not met - combination therapy should be initiated early 5
• Don't delay adding ezetimibe - waiting months on inadequate therapy increases cardiovascular risk 1
• Don't ignore the triglyceride elevation - while LDL-C is the primary target, triglycerides >300 mg/dL warrant specific attention 4
• Don't add gemfibrozil to rosuvastatin due to increased myopathy risk; fenofibrate is safer if fibrate therapy becomes necessary 4
• Don't assume the patient is non-adherent without assessment - some patients are true non-responders requiring combination therapy 1

Safety Monitoring

• Assess for muscle symptoms at each visit (myopathy risk with combination therapy remains low but requires monitoring) 4
• Check hepatic transaminases 4-6 weeks after adding ezetimibe 1
• The combination of rosuvastatin and ezetimibe has an established safety profile comparable to statin monotherapy 1