What are the guidelines for adding rosuvastatin to the treatment regimen of an adult patient with high cholesterol or at risk for cardiovascular disease?

Guidelines for Adding Rosuvastatin

Rosuvastatin should be initiated at 20-40 mg daily for high-intensity therapy in adults ≤75 years with established ASCVD or LDL-C ≥190 mg/dL, or at 5-10 mg daily for moderate-intensity therapy in primary prevention based on cardiovascular risk assessment. 1

Clinical Indications for Initiating Rosuvastatin

High-Intensity Therapy (20-40 mg daily)

Adults ≤75 years with established ASCVD should receive high-intensity rosuvastatin (20-40 mg daily), including those with acute coronary syndromes, MI, stable/unstable angina, coronary revascularization, stroke, TIA, or peripheral arterial disease. 1 This recommendation carries a Class I indication with Level I evidence. 2

Patients with LDL-C ≥190 mg/dL (≥4.9 mmol/L) aged 20-75 years require maximally tolerated statin therapy, which typically means high-intensity rosuvastatin 20-40 mg daily to achieve ≥50% LDL-C reduction. 2, 1

Very high-risk patients with multiple major ASCVD risk factors, diabetes, severe uncontrolled risk factors, or metabolic syndrome benefit from intensive LDL lowering to <70 mg/dL, which often requires high-intensity rosuvastatin. 1

Moderate-Intensity Therapy (5-10 mg daily)

For primary prevention in adults aged 40-75 years without established ASCVD, start rosuvastatin 5-10 mg daily based on cardiovascular risk assessment using tools that incorporate age, hsCRP ≥2 mg/L, and additional CV risk factors. 1, 3

Patients requiring 30-49% LDL-C reduction should receive rosuvastatin 5-10 mg daily, which is classified as moderate-intensity therapy. 1, 4

Dose Selection Algorithm

Starting Dose Determination

1. For established ASCVD (≤75 years): Start rosuvastatin 20 mg daily 1, 4
2. For LDL-C ≥190 mg/dL: Start rosuvastatin 20-40 mg daily 2, 1
3. For primary prevention (40-75 years): Start rosuvastatin 5-10 mg daily 1
4. For patients >75 years with ASCVD: Consider moderate-intensity therapy (10 mg daily) as there is no clear evidence of additional ASCVD event reduction from high-intensity therapy in this age group 1

Dose Titration Strategy

Assess LDL-C as early as 4 weeks after initiating rosuvastatin and adjust dosage if necessary. 3 If LDL-C remains ≥70 mg/dL on maximally tolerated statin therapy, add ezetimibe. 2, 5

For patients not achieving LDL-C goal <55 mg/dL (<1.4 mmol/L) after 4-6 weeks, immediately add ezetimibe to the statin regimen rather than relying on statin monotherapy alone. 4

Special Population Considerations

Asian Patients

Asian patients must start at 5 mg once daily due to significantly higher rosuvastatin plasma concentrations compared to white patients. 1, 3 Consider risks and benefits when treating Asian patients not adequately controlled at doses up to 20 mg once daily. 3

Severe Renal Impairment

In patients with severe renal impairment (CrCl <30 mL/min/1.73 m²) not on hemodialysis, start rosuvastatin at 5 mg once daily and do not exceed 10 mg daily. 1, 3 No dose adjustment is needed for mild to moderate renal impairment. 1

Pediatric Patients

For pediatric patients aged 8-10 years with heterozygous familial hypercholesterolemia (HeFH), use rosuvastatin 5-10 mg daily. 3 For patients aged 10 years and older with HeFH, use 5-20 mg daily. 3 For patients aged 7 years and older with homozygous familial hypercholesterolemia (HoFH), use 20 mg daily. 3

Drug Interaction Dose Modifications

Critical dose restrictions must be observed to prevent severe muscle toxicity:

• With cyclosporine, tacrolimus, everolimus, or sirolimus: Do not exceed 5 mg daily due to 7-fold increase in rosuvastatin exposure and severe risk of rhabdomyolysis 1, 3
• With teriflunomide, enasidenib, or capmatinib: Do not exceed 10 mg daily 3
• With fostamatinib: Do not exceed 20 mg daily 3
• With resmetirom for MASH/NASH: Limit to 20 mg daily 1

Administration Guidelines

Administer rosuvastatin as a single dose at any time of day, with or without food. 3 Swallow tablets whole. 3

When taking rosuvastatin with an aluminum and magnesium hydroxide combination antacid, administer rosuvastatin at least 2 hours before the antacid. 3

Common Pitfalls to Avoid

Do not automatically start all patients at 10 mg without considering ethnicity and renal function—Asian patients and those with severe renal impairment require the lower 5 mg starting dose to avoid excessive drug exposure and increased risk of myopathy. 1

Do not use simvastatin 80 mg due to increased myopathy risk if considering switching from another statin. 5

Do not delay treatment in patients with multiple ASCVD risk factors and significantly elevated LDL cholesterol—high-intensity therapy should be started from the outset. 5

Do not rely on statin monotherapy alone in very high-risk patients—combination therapy with ezetimibe should be initiated early if LDL-C goals are not met within 4-6 weeks. 4

Safety Profile

High-dose rosuvastatin has an acceptable safety profile with myopathy incidence <0.1% at recommended doses of 5-40 mg daily. 1 There is a slight increased risk of new-onset diabetes, particularly in patients with metabolic syndrome features. 1

Monitor for statin-associated muscle symptoms and check liver function tests if clinically indicated. 5 Both rosuvastatin and other statins have not shown adverse effects on cognition. 2