When should Rosuvastatin (rosuvastatin) be considered as adjunct therapy for patients with elevated cardiovascular risk?

Rosuvastatin as Adjunct Therapy for Elevated Cardiovascular Risk

Rosuvastatin should be considered as adjunct therapy when combined with ezetimibe in patients who fail to achieve LDL-C goals on maximally tolerated statin monotherapy, particularly in those with established atherosclerotic cardiovascular disease (ASCVD) or very high cardiovascular risk. 1

Primary Indications for Rosuvastatin Adjunct Therapy

High-Risk Patients Not at LDL-C Goal

Add ezetimibe 10 mg to rosuvastatin when LDL-C remains ≥70 mg/dL (≥1.8 mmol/L) despite maximally tolerated statin therapy in patients with ASCVD or very high cardiovascular risk. 1 This combination approach is superior to up-titrating rosuvastatin alone, providing greater LDL-C reductions with comparable or better tolerability. 1

• The combination of rosuvastatin with ezetimibe produces synergistic LDL-C reductions of 60-75%, compared to 50-55% with rosuvastatin monotherapy. 2
• In the ACTE trial, adding ezetimibe 10 mg to stable rosuvastatin 5 or 10 mg produced greater improvements in lipid profiles and better achievement of LDL-C goals compared with up-titrating rosuvastatin doses. 1
• The I-ROSETTE trial demonstrated that all fixed-dose combinations of ezetimibe/rosuvastatin achieved >50% reduction in mean LDL-C from baseline, with safety and tolerability comparable to rosuvastatin monotherapy. 1

Very High-Risk Patients Requiring Intensive Therapy

In patients with extremely high-risk conditions (recent myocardial infarction, multivessel coronary disease, or polyvascular disease), consider combination therapy with high-potency rosuvastatin, ezetimibe, and PCSK9-targeted therapy as first-line treatment. 1

• Target LDL-C <55 mg/dL (<1.4 mmol/L) in patients with clinical ASCVD. 1
• For patients with recurrent ASCVD events within 2 years on maximally tolerated statin therapy, consider an even lower LDL-C goal of <40 mg/dL (<1.0 mmol/L). 1

Familial Hypercholesterolemia

Rosuvastatin (20-40 mg) combined with ezetimibe should be used as initial therapy in adults with heterozygous familial hypercholesterolemia (HeFH) to achieve LDL-C goals. 1

• Maximally tolerated high-potency statins (rosuvastatin, atorvastatin, or pitavastatin) with or without ezetimibe and/or bempedoic acid should initially be used to achieve LDL-C goals. 1
• If LDL-C goals are not achieved with this combination, add PCSK9-targeted therapy. 1
• In pediatric patients aged 8 years and older with HeFH, rosuvastatin 5-20 mg daily is recommended (dose range depends on age). 3

Specific Clinical Scenarios

Acute Coronary Syndrome

In patients with non-ST elevation acute coronary syndrome, rosuvastatin 10 mg combined with ezetimibe 10 mg is superior to high-intensity rosuvastatin monotherapy (20 mg), providing greater LDL-C lowering with lower incidence of drug-related adverse events. 1, 4

Statin Intolerance

When patients cannot tolerate high-intensity statin therapy, adding ezetimibe to moderate-intensity rosuvastatin may be reasonable if LDL-C remains ≥70 mg/dL. 1

• This combination may potentially produce ASCVD risk reduction similar to high-intensity statin monotherapy, as demonstrated in post-ACS patients. 1
• At least three different statins should be tried before confirming clinically relevant statin-related muscle symptoms. 1

Patients with 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 once daily. 3

• Medication dosing requires adjustment based on renal function when combining rosuvastatin with other lipid-lowering agents. 5

Asian Patients

Initiate rosuvastatin at 5 mg once daily in Asian patients due to increased plasma concentrations, and carefully consider risks and benefits when treating doses up to 20 mg once daily. 3

Important Contraindications and Caveats

Heart Failure

Statins, including rosuvastatin, are not beneficial as adjunct therapy when prescribed solely for the diagnosis of heart failure in the absence of other indications for atherosclerotic vascular disease prevention. 1

• The CORONA and GISSI-HF trials showed no benefit of rosuvastatin 10 mg daily on primary outcomes in patients with heart failure. 1
• Routine use of statins for treatment of heart failure is not indicated outside current practice guidelines for primary and secondary prevention of atherosclerotic vascular disease. 1

Drug Interactions Requiring Dose Modifications

Specific dose limitations apply when rosuvastatin is used with certain concomitant medications: 3

• Do not exceed 5 mg once daily with cyclosporine
• Do not exceed 10 mg once daily with teriflunomide, enasidenib, or capmatinib
• Do not exceed 20 mg once daily with fostamatinib
• Administer rosuvastatin at least 2 hours before aluminum and magnesium hydroxide antacids

Monitoring Requirements

Monitor hepatic aminotransferases, creatine kinase, glucose, and creatinine before starting therapy and during treatment as clinically indicated. 1

• Hepatic aminotransferases should be monitored in patients with increased risk of hepatotoxicity (history of liver disease, excess alcohol, or adverse drug interactions). 1
• Measure creatine kinase if musculoskeletal symptoms are reported. 1
• Monitor glucose or HbA1c if risk factors for diabetes are present. 1

Treatment Algorithm

The stepwise approach for rosuvastatin adjunct therapy should follow this sequence: 1, 5, 4

1. Start with high-intensity rosuvastatin monotherapy (20-40 mg) for patients with ASCVD or very high cardiovascular risk
2. Add ezetimibe 10 mg if LDL-C target not achieved after 4-6 weeks
3. Add PCSK9 inhibitor if LDL-C remains elevated despite maximally tolerated statin plus ezetimibe
4. For extremely high-risk patients, consider upfront combination therapy with rosuvastatin, ezetimibe, and PCSK9 inhibitor

Assess LDL-C as early as 4 weeks after initiating or adjusting rosuvastatin therapy and adjust dosage accordingly. 3