Differences Between Atorvastatin, Simvastatin, and Rosuvastatin
Rosuvastatin is the most potent statin, followed by atorvastatin, then simvastatin—with rosuvastatin requiring doses 3-3.5 times lower than atorvastatin and 7-8 times lower than simvastatin to achieve equivalent LDL-C reductions. 1
Potency and LDL-C Lowering Efficacy
High-Intensity Statin Therapy (≥50% LDL-C Reduction)
Only rosuvastatin and atorvastatin can achieve high-intensity statin therapy effects:
- Rosuvastatin 20-40 mg achieves ≥50% LDL-C reduction 2
- Atorvastatin 40-80 mg achieves ≥50% LDL-C reduction 2
- Simvastatin cannot achieve high-intensity effects at any dose—the maximum 80 mg dose is not recommended by the FDA due to increased myopathy and rhabdomyolysis risk 2
Moderate-Intensity Statin Therapy (30-49% LDL-C Reduction)
All three statins can provide moderate-intensity effects at specific doses:
- Rosuvastatin 5-10 mg reduces LDL-C by 30-49% 2, 3
- Atorvastatin 10-20 mg reduces LDL-C by 30-49% 2, 3
- Simvastatin 20-40 mg reduces LDL-C by 30-49% 2, 3
Low-Intensity Statin Therapy (<30% LDL-C Reduction)
- Simvastatin 10 mg reduces LDL-C by <30% 2
- Neither rosuvastatin nor atorvastatin are typically used for low-intensity therapy 2
Dose Equivalency for Equal LDL-C Reduction
The VOYAGER meta-analysis established precise dose equivalencies:
- Rosuvastatin 5 mg (39% LDL-C reduction) = Atorvastatin 15 mg = Simvastatin 39 mg 1
- Rosuvastatin 10 mg (44% LDL-C reduction) = Atorvastatin 29 mg = Simvastatin 72 mg 1
- Rosuvastatin 20 mg (50% LDL-C reduction) = Atorvastatin 70 mg; simvastatin 80 mg cannot achieve this 1
- Rosuvastatin 40 mg (55% LDL-C reduction) cannot be matched by maximum doses of atorvastatin or simvastatin 1
Comparative Efficacy Studies
Head-to-head trials demonstrate rosuvastatin superiority:
- In the STELLAR trial, rosuvastatin 10-40 mg achieved LDL-C goals (<100 mg/dL) in 53-80% of patients, compared to 18-70% with atorvastatin and 8-53% with simvastatin 4
- At comparable doses, rosuvastatin was more effective than atorvastatin or simvastatin in reducing LDL-C, triglycerides, and total cholesterol in usual care settings 5
- Rosuvastatin 10 mg achieved higher LDL-C goal attainment than atorvastatin 10 or 20 mg 5
HDL-C Effects
Rosuvastatin demonstrates superior HDL-C raising effects:
- Rosuvastatin 40 mg increased large alpha-1 HDL by 24% versus 12% with atorvastatin 80 mg (p<0.001) 6
- Rosuvastatin 40 mg increased alpha-2 HDL by 13% versus 4% with atorvastatin 80 mg (p<0.001) 6
- In patients with low HDL-C, rosuvastatin increased alpha-1 by 32% versus 11% with atorvastatin 6
Safety Considerations
Critical safety difference for simvastatin:
- Simvastatin 80 mg should never be initiated or titrated to due to FDA warnings about increased myopathy and rhabdomyolysis risk 2
- This effectively limits simvastatin's maximum safe dose to 40 mg, further restricting its potency compared to rosuvastatin and atorvastatin 2
Clinical Application Algorithm
For patients requiring ≥50% LDL-C reduction (high-intensity therapy):
For patients requiring 30-49% LDL-C reduction (moderate-intensity therapy):
- Use rosuvastatin 5-10 mg OR atorvastatin 10-20 mg OR simvastatin 20-40 mg 2, 3
- Rosuvastatin requires the lowest dose to achieve equivalent effects 1
For patients requiring <30% LDL-C reduction (low-intensity therapy):
- Simvastatin 10 mg is appropriate 2
- Rosuvastatin and atorvastatin are not typically used at these lower intensities 2
Key Clinical Pitfalls
Common prescribing errors to avoid:
- Do not assume equal doses of different statins produce equal effects—rosuvastatin is 3-8 times more potent than the others 1
- Do not prescribe simvastatin 80 mg under any circumstances due to myopathy risk 2
- Do not use simvastatin when high-intensity statin therapy is indicated, as it cannot achieve ≥50% LDL-C reduction safely 2, 1
- Individual responses vary in clinical practice despite population-level estimates 2