Atorvastatin and Rosuvastatin Are Preferred Over Pravastatin for LDL Cholesterol Reduction
Both atorvastatin and rosuvastatin are superior to pravastatin for lowering LDL cholesterol, with rosuvastatin demonstrating the greatest potency, followed by atorvastatin, then pravastatin. 1, 2
Comparative LDL-Lowering Efficacy
Dose-Equivalent Reductions
The evidence clearly demonstrates a hierarchy of statin potency:
Rosuvastatin 5-10 mg achieves approximately 39-45% LDL reduction, comparable to atorvastatin 10-20 mg (39-43% reduction) but substantially greater than pravastatin 40-80 mg (34% reduction) 1
Atorvastatin 10 mg reduces LDL by 39%, while pravastatin 40 mg achieves only 34% reduction 1
Rosuvastatin reduces LDL cholesterol 8.2% more than atorvastatin across equivalent dose ranges, 26% more than pravastatin, and 12-18% more than simvastatin 2
High-Intensity Therapy Comparison
For patients requiring aggressive LDL lowering:
Atorvastatin 40-80 mg achieves >50% LDL reduction (classified as high-intensity statin therapy) 1
Rosuvastatin 20-40 mg achieves >50% LDL reduction (classified as high-intensity statin therapy) 1
Pravastatin 40-80 mg achieves only 30-50% LDL reduction (classified as moderate-intensity therapy, never reaching high-intensity threshold) 1
Clinical Outcomes Evidence
PROVE IT Trial: Atorvastatin vs Pravastatin
The landmark PROVE IT trial directly compared these agents in high-risk patients:
Atorvastatin 80 mg reduced composite cardiovascular endpoints by 16% compared to pravastatin 40 mg (22.4% vs 26.3% event rate, p<0.005) over 2 years 1
Atorvastatin achieved median LDL of 62 mg/dL versus pravastatin's 95 mg/dL (33 mg/dL difference representing 35% greater reduction) 1
Both agents were well-tolerated with no cases of rhabdomyolysis in either group 1
STELLAR Trial: Rosuvastatin Superiority
The STELLAR trial demonstrated rosuvastatin's superior efficacy:
82-89% of patients on rosuvastatin 10-40 mg achieved ATP III LDL goals versus 69-85% on atorvastatin 10-80 mg 2
Rosuvastatin 10 mg was more effective than atorvastatin 10 mg, pravastatin 10-40 mg, and simvastatin 10-40 mg (all p<0.002) 3
Rosuvastatin demonstrated superior HDL elevation (+7.7% to +9.6%) compared to all comparators (+2.1% to +6.8%) 2
Guideline-Based Recommendations
For High-Risk Patients (Established ASCVD, Diabetes)
Use high-intensity statin therapy: atorvastatin 40-80 mg or rosuvastatin 20-40 mg 1
Pravastatin cannot achieve high-intensity classification and should not be used when high-intensity therapy is indicated 1
Target LDL <100 mg/dL, with optional goal <70 mg/dL for very high-risk patients 1
For Moderate-Risk Patients (10-Year ASCVD Risk 7.5-20%)
Use moderate- to high-intensity statin therapy: atorvastatin 10-80 mg or rosuvastatin 5-40 mg preferred over pravastatin 1, 4
- Rosuvastatin 5-10 mg or atorvastatin 10-20 mg achieves greater LDL reduction than pravastatin 40-80 mg 1
For Primary Prevention in Lower-Risk Patients
Moderate-intensity therapy is appropriate, but atorvastatin 10-20 mg or rosuvastatin 5-10 mg are more effective than pravastatin 40 mg 1, 4
Additional Lipid Benefits Beyond LDL
Rosuvastatin provides superior non-HDL cholesterol and triglyceride reduction compared to pravastatin 2
Rosuvastatin reduced small dense LDL cholesterol by 53% versus atorvastatin's 46% at maximal doses 5
Both atorvastatin and rosuvastatin significantly outperform pravastatin for total cholesterol/HDL ratio reduction 5
Safety Considerations
All three statins demonstrate similar safety profiles with rare serious adverse events 1, 2
Atorvastatin 80 mg showed 3.3% rate of >3-fold ALT elevation versus 1.1% with pravastatin 40 mg 1
No threshold has been identified below which LDL lowering causes harm, and very low LDL levels (<70 mg/dL) are safe and beneficial 1, 6
Monitor liver enzymes and assess for muscle symptoms with all statins 4
Common Pitfalls to Avoid
Do not use pravastatin when high-intensity statin therapy is indicated, as it cannot achieve the required >50% LDL reduction even at maximum doses 1
Do not assume equivalent dosing across statins: pravastatin 40 mg is roughly equivalent to only atorvastatin 10 mg in LDL-lowering effect 1
Do not hesitate to use atorvastatin 80 mg or rosuvastatin 40 mg in very high-risk patients who require intensive LDL lowering to achieve goals <70 mg/dL 1, 6
Pharmacokinetic Differences
Rosuvastatin has the longest half-life (19 hours) and is hydrophilic with minimal cytochrome P450 metabolism, reducing drug interaction potential 7
Atorvastatin is lipophilic with moderate half-life and undergoes cytochrome P450 metabolism, requiring consideration of drug interactions 7
Pravastatin is hydrophilic but has the shortest half-life (1-3 hours) and lowest bioavailability, contributing to its lower potency 7