At what dose should rosuvastatin (a statin) be initiated in a patient with hypercholesterolemia or at risk for cardiovascular disease, considering their medical history and potential for impaired renal function?

Rosuvastatin Initiation and Dosing

For most patients with hypercholesterolemia or cardiovascular disease risk, initiate rosuvastatin at 10-20 mg once daily, with the specific dose determined by cardiovascular risk category and renal function. 1, 2

Dosing by Clinical Indication

Secondary Prevention (Established ASCVD)

• Initiate high-intensity therapy with rosuvastatin 20-40 mg once daily for patients with established atherosclerotic cardiovascular disease (history of MI, ACS, stroke, or symptomatic PAD) 1, 3
• This achieves ≥50% LDL-C reduction, which is the target for secondary prevention 1
• Assess LDL-C as early as 4 weeks after initiation and adjust dosage accordingly 2

Primary Prevention with Severe Hypercholesterolemia (LDL-C ≥190 mg/dL)

• Start with maximally tolerated statin therapy, typically rosuvastatin 20-40 mg daily, in patients aged 20-75 years 1
• If <50% LDL-C reduction is achieved or LDL-C remains ≥100 mg/dL on maximally tolerated statin, add ezetimibe 1

Primary Prevention with Moderate Risk

• Initiate rosuvastatin 5-10 mg once daily for patients with 10-year ASCVD risk ≥7.5% and LDL-C 70-189 mg/dL 1
• The standard starting dose of 10 mg reduces LDL-C by approximately 45% 1, 4
• Rosuvastatin 5 mg reduces LDL-C by 39-45% and may be sufficient for lower-risk patients 1, 4

Diabetes Mellitus

• Start rosuvastatin 10-20 mg daily (moderate-to-high intensity) in patients aged 40-75 years with diabetes 1

Dosing Modifications for Renal Impairment

Severe Renal Impairment (CrCl <30 mL/min, not on dialysis)

• Initiate at 5 mg once daily; do not exceed 10 mg once daily 3, 5, 6, 2
• Plasma concentrations are 2-fold higher in severe renal impairment, increasing myopathy risk 3

Hemodialysis Patients

• Initiate at 5 mg daily; maximum 10 mg daily if statin therapy is already established 5, 6
• Do not initiate new statin therapy in patients already on dialysis, but continue if already taking 5, 6
• The AURORA trial showed no cardiovascular benefit with rosuvastatin 10 mg in hemodialysis patients 3, 5

Moderate Renal Impairment (CrCl 30-60 mL/min)

• Standard dosing can be used (5-40 mg daily based on indication), but monitor closely for adverse effects 6
• Consider moderate-intensity therapy (5-10 mg) combined with ezetimibe rather than high-intensity monotherapy 1, 6

Special Populations

Asian Patients

• Initiate at 5 mg once daily regardless of indication due to 2-fold higher plasma concentrations 3, 2
• Consider risks and benefits if not adequately controlled at doses up to 20 mg daily 2

Elderly Patients (≥75 years)

• Secondary prevention: Continue high-intensity therapy (20-40 mg) if already tolerating and low risk of competing morbidities 1
• Primary prevention: Consider moderate-intensity therapy (10 mg) if 10-year ASCVD risk ≥7.5% 1
• Rosuvastatin reduced cardiovascular events by 26% in patients ≥70 years in the JUPITER trial 1

Heart Failure with Reduced Ejection Fraction

• Do not initiate rosuvastatin solely for heart failure without other indications 1
• The CORONA and GISSI-HF trials showed no benefit with rosuvastatin 10 mg in heart failure patients 1

Combination Therapy Strategy

When to Add Ezetimibe

• Add ezetimibe 10 mg if LDL-C remains ≥70 mg/dL on maximally tolerated statin in patients with ASCVD 1
• Rosuvastatin 5-10 mg plus ezetimibe 10 mg is superior to rosuvastatin 20 mg monotherapy for LDL-C reduction with fewer adverse effects 1
• This combination is particularly useful when high-intensity statin doses cannot be tolerated 1

Common Pitfalls to Avoid

• Do not use rosuvastatin 40 mg in patients with severe renal impairment (CrCl <30 mL/min)—this dramatically increases myopathy risk 3, 2
• Do not use simvastatin 80 mg as an alternative—the FDA warns against initiation or titration to this dose due to myopathy risk 1
• Do not fail to assess LDL-C response—check levels at 4-12 weeks and adjust therapy accordingly 2
• Do not overlook drug interactions—rosuvastatin is not metabolized by CYP3A4, making it safer with many concomitant medications 7

Cost-Effectiveness Consideration

• Rosuvastatin 10 mg every-other-day may be considered in low-risk patients when cost is prohibitive, achieving 39% LDL-C reduction versus 48% with daily dosing 8
• However, this approach is not guideline-recommended and should only be used when standard therapy is financially inaccessible 8