What is the recommended moderate intensity statin (HMG-CoA reductase inhibitor) therapy for a patient with a history of heart disease, diabetes, or stroke, and impaired renal function?

Moderate-Intensity Statin Therapy for High-Risk Patients with Impaired Renal Function

For patients with diabetes, heart disease, or stroke and impaired renal function, moderate-intensity statin therapy consists of atorvastatin 10-20 mg, rosuvastatin 5-10 mg, pravastatin 40-80 mg, or fluvastatin XL 80 mg once daily, with dose adjustments required for severe renal impairment. 1

Specific Moderate-Intensity Statin Options

The following regimens achieve 30-49% LDL cholesterol reduction 1:

• Atorvastatin 10-20 mg once daily
• Rosuvastatin 5-10 mg once daily
• Pravastatin 40-80 mg once daily
• Fluvastatin XL 80 mg once daily
• Simvastatin 20-40 mg once daily
• Lovastatin 40 mg once daily
• Pitavastatin 1-4 mg once daily

Critical Dosing Adjustments for Renal Impairment

For severe renal impairment (CrCl <30 mL/min/1.73 m²) not on hemodialysis, rosuvastatin should start at 5 mg once daily and not exceed 10 mg once daily. 2 This is a critical safety consideration as patients with renal impairment face increased risk of myopathy and rhabdomyolysis with higher statin doses. 2

No dosage adjustments are required for mild to moderate renal impairment. 2

When to Consider High-Intensity Therapy Instead

While the question asks about moderate-intensity statins, it's important to recognize that patients with established atherosclerotic cardiovascular disease (heart disease or stroke) should receive high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) to achieve ≥50% LDL cholesterol reduction and target LDL <70 mg/dL. 1

For patients aged 40-75 years with diabetes but without established cardiovascular disease, moderate-intensity therapy is appropriate. 1 However, those with multiple additional ASCVD risk factors should receive high-intensity therapy. 1

Managing Statin Intolerance

If patients cannot tolerate the intended statin intensity due to side effects, use the maximum tolerated statin dose rather than discontinuing therapy entirely. 3 Evidence demonstrates cardiovascular benefit even with extremely low, less-than-daily statin doses. 1, 3

For patients not achieving LDL goals on maximum tolerated statin, consider adding ezetimibe (preferred due to lower cost) or PCSK9 inhibitors. 1, 3

Monitoring and Titration

Assess LDL cholesterol 4-12 weeks after initiating or changing statin therapy to evaluate response and medication adherence. 3, 2 Meta-analyses demonstrate a 9% reduction in all-cause mortality and 13% reduction in vascular mortality for each 39 mg/dL reduction in LDL cholesterol, with benefits linearly related to LDL reduction without a lower threshold. 1

Important Drug Interactions in Renal Disease

Several medications commonly used in patients with renal impairment require rosuvastatin dose limitations 2:

• Cyclosporine: Do not exceed 5 mg once daily
• Teriflunomide or enasidenib: Do not exceed 10 mg once daily
• Gemfibrozil: Avoid concomitant use; if necessary, start at 5 mg and do not exceed 10 mg once daily

Common Pitfalls to Avoid

Do not use high-intensity statins without dose adjustment in severe renal impairment, as this significantly increases myopathy risk. 2 Risk factors for myopathy include age ≥65 years, uncontrolled hypothyroidism, renal impairment, and concomitant use of certain medications. 2

Asian patients require special consideration, with an initial dose of 5 mg rosuvastatin once daily due to increased plasma concentrations, and careful risk-benefit assessment when considering doses above 20 mg daily. 2