What are the differences between atorvastatin (Lipitor) and rosuvastatin (Crestor) in reducing low-density lipoprotein (LDL) levels in a patient with a history of cerebrovascular accident (CVA), possible ischemic heart disease (IHD), hyperglycemia-induced seizures, and diabetes mellitus (DM)?

LDL-C Reduction: Rosuvastatin vs Atorvastatin

Rosuvastatin is more potent than atorvastatin at reducing LDL-C levels, with rosuvastatin 20 mg providing equivalent or superior LDL-C reduction compared to atorvastatin 40-80 mg. 1, 2, 3

Comparative Efficacy by Dose

High-Intensity Statin Dosing

• Rosuvastatin 20 mg reduces LDL-C by approximately 52-55%, which is classified as high-intensity statin therapy and achieves similar or greater reductions than atorvastatin 40-80 mg 1, 2, 4
• Atorvastatin 40 mg reduces LDL-C by approximately 47-50%, while atorvastatin 80 mg reduces LDL-C by approximately 50-52% 1, 5
• In direct head-to-head comparison, rosuvastatin 40 mg reduced LDL-C by 52% versus atorvastatin 80 mg which reduced LDL-C by 50% 2, 3

Milligram-for-Milligram Comparison

• Rosuvastatin 10 mg produces approximately 45-52% LDL-C reduction, significantly more than atorvastatin 10 mg which produces 37% reduction 2, 6
• Rosuvastatin 20 mg produces approximately 52-55% LDL-C reduction, significantly more than atorvastatin 20 mg which produces 43% reduction 2, 4
• Rosuvastatin 40 mg produces approximately 55-63% LDL-C reduction, significantly more than atorvastatin 40 mg which produces 48% reduction 2, 3, 6

Additional Lipid Effects Beyond LDL-C

Small Dense LDL Particles

• Rosuvastatin 40 mg reduces small dense LDL cholesterol by 53% versus atorvastatin 80 mg which reduces it by 46% (p<0.01), a clinically meaningful difference for patients with diabetes and metabolic syndrome 3
• Small dense LDL particles are particularly atherogenic, making this differential effect relevant for your patient with diabetes and cerebrovascular disease 3

Triglyceride Reduction

• Both statins produce similar triglyceride reductions: rosuvastatin reduces TG by 24-32% versus atorvastatin by 24-28% at maximal doses 2, 3, 4
• A 2025 meta-analysis found rosuvastatin reduced TG by 31.98 mg/dL versus atorvastatin by 24.76 mg/dL, though this difference is modest 4

HDL-C Increase

• Rosuvastatin increases HDL-C more effectively than atorvastatin: rosuvastatin increases HDL-C by 8-11% versus atorvastatin by 4-7% 2, 3, 4
• The 2025 meta-analysis confirmed rosuvastatin raised HDL by 3.87 mg/dL versus atorvastatin by 1.85 mg/dL 4

Clinical Application for Your Patient

Recommended Approach for CVA + Possible IHD + Diabetes

• Start with high-intensity statin therapy immediately: either rosuvastatin 20-40 mg OR atorvastatin 40-80 mg 1, 7
• Target LDL-C <55 mg/dL (1.4 mmol/L) with ≥50% reduction from baseline, as this patient has established ASCVD (CVA) plus diabetes, qualifying as very high-risk 1, 7
• If choosing rosuvastatin, start with 20 mg daily as this provides high-intensity therapy (≥50% LDL-C reduction) with excellent tolerability 1, 2
• If choosing atorvastatin, start with 40-80 mg daily as both doses are classified as high-intensity therapy 1, 5, 7

When to Prefer Rosuvastatin Over Atorvastatin

• When maximal LDL-C reduction is needed: rosuvastatin 20 mg achieves similar LDL-C reduction to atorvastatin 80 mg, potentially avoiding the higher adverse event rate of atorvastatin 80 mg 2, 3
• When small dense LDL reduction is a priority: rosuvastatin provides superior reduction of these particularly atherogenic particles in patients with diabetes 3
• When HDL-C increase is desired: rosuvastatin produces greater HDL-C elevation 3, 4
• When drug interactions are a concern: rosuvastatin undergoes minimal CYP450 metabolism (only 10% via CYP2C9), whereas atorvastatin is extensively metabolized via CYP3A4 6, 8

When to Prefer Atorvastatin Over Rosuvastatin

• When extensive cardiovascular outcomes data is prioritized: atorvastatin 80 mg has robust evidence from SPARCL trial specifically for stroke prevention, demonstrating 16% reduction in recurrent stroke 7
• When cost is a significant barrier: atorvastatin is available as generic and typically less expensive 8
• When the patient has prior hemorrhagic stroke: use caution with any high-intensity statin, but atorvastatin 80 mg has specific safety data in this population 7

Combination Therapy if Targets Not Met

• Add ezetimibe 10 mg daily if LDL-C remains ≥70 mg/dL on maximally tolerated statin, providing an additional 15-25% LDL-C reduction 1, 9
• Add PCSK9 inhibitor if LDL-C remains ≥55 mg/dL on maximally tolerated statin plus ezetimibe, providing an additional 50-60% LDL-C reduction 1, 9

Safety Considerations

• Both statins have similar safety profiles at their respective high-intensity doses, with myalgia, elevated liver enzymes, and new-onset diabetes being the primary concerns 1, 10
• Monitor for new-onset diabetes symptoms as both statins increase diabetes risk by approximately 0.2% per year, though this is outweighed by cardiovascular benefits 5, 10
• Check liver enzymes at baseline and as clinically indicated, and assess for muscle symptoms at each visit 5, 7
• Rosuvastatin has fewer drug-drug interactions due to minimal CYP450 metabolism, but significant interactions still occur with cyclosporine, gemfibrozil, and warfarin 6, 8

Critical Pitfall to Avoid

• Do not use moderate-intensity statin therapy (such as atorvastatin 10-20 mg or rosuvastatin 5-10 mg) for a patient with established ASCVD and diabetes—this patient requires high-intensity therapy to achieve guideline-recommended targets 1, 7