What are the differences in side effect profile, tolerability, and efficacy between atorvastatin (Lipitor) and rosuvastatin (Crestor)?

Comparison of Atorvastatin vs Rosuvastatin: Side Effect Profile, Tolerability, and Efficacy

Rosuvastatin demonstrates superior LDL-C lowering efficacy compared to atorvastatin at equivalent doses, while both medications have similar side effect profiles and tolerability. 1, 2

Efficacy Comparison

• Rosuvastatin provides greater LDL-C reduction than atorvastatin at comparable doses: 10mg rosuvastatin reduces LDL-C by approximately 45% versus 39% with 10mg atorvastatin 3, 4
• At maximal doses, rosuvastatin 40mg reduces LDL-C by 53% compared to 50% with atorvastatin 80mg 1
• Rosuvastatin is more effective at increasing HDL-C (6.4%) compared to atorvastatin (3.1%) at comparable doses 2
• More patients achieve recommended LDL-C goals with rosuvastatin compared to equivalent doses of atorvastatin (68.8% vs 62.5% for NCEP ATP III goals) 2
• Rosuvastatin has demonstrated superior efficacy in reducing small dense LDL cholesterol particles (-53% vs -46% with atorvastatin) 1

Dosing Equivalence

• Standard dosing for LDL-C reduction of 30-40%:
  • Atorvastatin 10mg reduces LDL-C by approximately 39% 3
  • Rosuvastatin 5-10mg reduces LDL-C by approximately 39-45% 3
• High-intensity dosing for LDL-C reduction ≥50%:
  • Atorvastatin 40-80mg 3
  • Rosuvastatin 20-40mg 3

Side Effect Profile and Tolerability

• Both statins have similar overall tolerability profiles with comparable incidence of adverse events (rosuvastatin 10mg: 27.5%; atorvastatin 20mg: 26.1%) 2
• Statin-associated muscle symptoms (SAMS) occur with both medications at similar rates 4
• Risk factors for statin-related side effects with both medications include:
  • Female gender
  • Advanced age
  • Asian descent
  • Multiple comorbidities 4
• Neither medication shows significant differences in risk of rhabdomyolysis, liver dysfunction, or renal insufficiency at standard doses 2
• Both statins may modestly increase the risk of new-onset diabetes, particularly in patients with pre-existing risk factors for diabetes 3

Pharmacokinetic Differences

• Rosuvastatin has a longer half-life (19 hours) compared to atorvastatin (14 hours), which may affect dosing frequency options 4
• Atorvastatin is primarily metabolized by CYP3A4, while rosuvastatin relies more on CYP2C9, leading to different drug interaction profiles 4
• Rosuvastatin is more hydrophilic than atorvastatin, which may contribute to differences in tissue penetration and side effect profiles 4

Clinical Application

• For high-risk patients requiring intensive LDL-C lowering (≥50%), rosuvastatin 20-40mg or atorvastatin 40-80mg are recommended 3
• For patients with statin intolerance, consider:
  1. Temporary discontinuation until symptoms resolve, then rechallenge 4
  2. Dose reduction or alternate-day dosing (particularly effective with long half-life statins like rosuvastatin) 4
  3. Switching between statins with different metabolic pathways (e.g., from atorvastatin to rosuvastatin if CYP3A4 drug interactions are a concern) 4

Special Considerations

• In patients with significant drug interactions involving CYP3A4 inhibitors, rosuvastatin may be preferred over atorvastatin 4
• For patients requiring modest LDL-C reduction (30-40%), lower doses of either statin are appropriate, with rosuvastatin being more potent on a milligram-per-milligram basis 3, 5
• When maximum statin therapy is insufficient to reach LDL-C goals, combination with ezetimibe is recommended before considering PCSK9 inhibitors 3

Both atorvastatin and rosuvastatin are effective and generally well-tolerated statins, with rosuvastatin demonstrating greater LDL-C lowering efficacy at equivalent doses while maintaining a similar safety profile.