What is the appropriate use of Crestor (rosuvastatin) in cholesterol-lowering therapy?

Appropriate Use of Rosuvastatin (Crestor) in Cholesterol-Lowering Therapy

Rosuvastatin is a high-intensity statin that should be used based on cardiovascular risk assessment, with doses of 5-40mg daily to achieve target LDL-C reductions of ≥50% in high-risk patients and 30-49% in moderate-risk patients. 1

Indications for Rosuvastatin

• FDA-approved for reducing the risk of major adverse cardiovascular events in adults without established coronary heart disease who are at increased risk based on age, high-sensitivity C-reactive protein ≥2 mg/L, and at least one additional CV risk factor 2
• Indicated as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia 2
• Approved to reduce LDL-C and slow the progression of atherosclerosis in adults 2
• Indicated for heterozygous familial hypercholesterolemia in adults and pediatric patients aged 8 years and older 2
• Used for homozygous familial hypercholesterolemia in adults and pediatric patients aged 7 years and older 2
• Indicated for primary dysbetalipoproteinemia and hypertriglyceridemia in adults 2

Dosing Recommendations by Risk Category

Primary Prevention (No Established ASCVD)

• Ages 40-75 years with risk factors:
  • Moderate-intensity statin therapy (rosuvastatin 5-10mg) for those with 10-year ASCVD risk of 7.5-10% 1
  • High-intensity statin therapy (rosuvastatin 20-40mg) for those with 10-year ASCVD risk ≥10% or with diabetes 1
• Ages 20-39 years: Consider statin therapy if additional ASCVD risk factors are present 1
• Ages >75 years: Continue statin if already on therapy; individualized decision for initiation 1

Secondary Prevention (Established ASCVD)

• High-intensity statin therapy (rosuvastatin 20-40mg) to achieve LDL-C reduction of ≥50% 1
• Target LDL-C of <70 mg/dL (<1.8 mmol/L) or even <55 mg/dL (<1.4 mmol/L) for very high-risk patients 1

Dosing Considerations

• Standard dosing range: 5-40mg once daily 2
• High-intensity dosing: Rosuvastatin 20-40mg (achieves ≥50% LDL-C reduction) 1
• Moderate-intensity dosing: Rosuvastatin 5-10mg (achieves 30-49% LDL-C reduction) 1
• Asian patients: Start with 5mg due to increased plasma concentrations; maximum recommended dose is 20mg 2
• Severe renal impairment: Start with 5mg; do not exceed 10mg 2
• Drug interactions: Dose adjustments needed with cyclosporine, teriflunomide, enasidenib, capmatinib, and fostamatinib 2

Efficacy

• Rosuvastatin 10-40mg reduces LDL-C by 52-63% in patients with hypercholesterolemia 3, 4
• Increases HDL-C by up to 14% and reduces triglycerides by up to 28% 4
• More effective than equivalent doses of atorvastatin, simvastatin, and pravastatin in reducing LDL-C 5, 6
• In the JUPITER trial, rosuvastatin 20mg daily demonstrated significant reduction in cardiovascular events in primary prevention patients with elevated hsCRP 1

Combination Therapy

• If LDL-C goals are not achieved with maximum tolerated rosuvastatin dose, add ezetimibe 1
• The combination of rosuvastatin with ezetimibe provides greater LDL-C reduction than up-titration of rosuvastatin alone 1
• Fixed-dose combinations of ezetimibe/rosuvastatin have shown >50% reduction in LDL-C levels with comparable safety to rosuvastatin monotherapy 1
• For patients with diabetes or metabolic disorders, consider combination therapy with rosuvastatin 20mg (or lower dose) and ezetimibe to reduce LDL-C without increasing risk of new-onset diabetes 1
• In very high-risk patients not reaching targets with statin plus ezetimibe, consider adding PCSK9 inhibitors 1

Safety Considerations

• Most common adverse effects include headache, nausea, myalgia, asthenia, and constipation 2
• Monitor for myopathy and rhabdomyolysis, especially in patients >65 years, with renal impairment, or on certain concomitant medications 2
• Risk factors for adverse effects include Asian ethnicity, severe renal impairment, and drug interactions 2
• Liver function tests should be performed before initiating therapy and as clinically indicated thereafter 2
• Discontinue if serious hepatic injury with clinical symptoms occurs 2

Follow-Up and Monitoring

• Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating therapy 2
• Adjust dosage based on LDL-C response and tolerability 2
• Regular monitoring of lipid levels and side effects is essential for optimal management 1

Special Populations

• Diabetes: High-intensity statin therapy recommended for patients aged 40-75 years with diabetes 1
• Severe hypercholesterolemia (LDL-C ≥190 mg/dL): High-intensity statin therapy is indicated 1
• Pediatric patients: Approved for HeFH (ages ≥8 years) and HoFH (ages ≥7 years) with specific dosing recommendations 2