What is the difference between simvastatin and atorvastatin?

Difference Between Simvastatin and Atorvastatin

Atorvastatin is 2 to 4 times more potent than simvastatin at equivalent doses for reducing LDL cholesterol, total cholesterol, and triglycerides, while simvastatin produces greater HDL cholesterol increases, particularly at maximum doses. 1

Potency and LDL-Lowering Efficacy

The key clinical difference lies in lipid-lowering potency, with dose equivalence between atorvastatin and simvastatin ranging from 1:2 to 1:4. 1

• Atorvastatin 10 mg produces significantly greater LDL-C reduction (37.0-37.2%) compared to simvastatin 10 mg (28.9-29.6%) and is comparable to or exceeds simvastatin 20 mg (33.8%) 2, 3
• At starting doses, atorvastatin 10 mg achieves LDL-C reductions similar to simvastatin 20-40 mg 4, 5
• The ASAP trial demonstrated that atorvastatin 80 mg decreased carotid intima-media thickness over 2 years, while simvastatin 40 mg daily resulted in increased carotid IMT in patients with familial hypercholesterolemia 5

HDL Cholesterol Effects

Simvastatin demonstrates superior HDL-raising effects compared to atorvastatin, with the greatest advantage at maximum doses. 6

• Simvastatin 80 mg produces significantly greater HDL-C increases than atorvastatin 80 mg (weighted mean difference of -4.35%; 95% CI, -5.64 to -3.08) 1
• At comparable doses (simvastatin 40-80 mg vs atorvastatin 20-80 mg), simvastatin consistently produces greater increases in HDL cholesterol and apolipoprotein A-I 6
• This HDL advantage occurs without any apparent dose-equivalence point between the two statins 1

Triglyceride Reduction

Atorvastatin produces significantly greater triglyceride reductions than simvastatin at equivalent doses. 2

• Atorvastatin 10 mg reduces triglycerides by 22.1% compared to 16.0% with simvastatin 10 mg (p < 0.0001) 2
• This triglyceride-lowering advantage is consistent across the dose range and represents a 2-4 fold greater potency for atorvastatin 1

Cardiovascular Outcomes

High-dose atorvastatin (80 mg) demonstrates superior cardiovascular event reduction compared to moderate-dose simvastatin in patients with carotid stenosis and acute coronary syndromes. 5

• In patients with carotid stenosis, atorvastatin 80 mg reduced stroke risk by 33% (HR 0.67,95% CI 0.47-0.94; p=0.02), major coronary events by 43% (HR 0.57,95% CI 0.32-1.00; p=0.05), and subsequent carotid revascularization by 56% (HR 0.44,95% CI 0.24-0.79; p=0.006) 5
• The PROVE-IT trial showed atorvastatin 80 mg reduced major cardiovascular events by 16% compared to pravastatin 40 mg in acute coronary syndrome patients 5

Safety Profile Differences

At maximum doses, simvastatin 80 mg carries higher myopathy risk, while atorvastatin 80 mg has higher rates of hepatotoxicity and gastrointestinal side effects. 5, 6

Simvastatin Safety Concerns:

• Simvastatin 80 mg is associated with significantly increased myopathy risk, with the SEARCH trial identifying 53 cases of myopathy with 80 mg versus only 3 cases with 20 mg (relative risk 8.8; 95% CI 4.2-18.4) 5
• The FDA recommends limiting simvastatin to 20 mg daily when combined with amiodarone due to drug interactions 5
• Maximum simvastatin dose should not exceed 40 mg when combined with amlodipine, and 10 mg when combined with verapamil or diltiazem 7

Atorvastatin Safety Concerns:

• Atorvastatin 80 mg produces a 6-fold increase in liver enzyme elevations (1.2% vs 0.2% with 10 mg; p < 0.001) 5
• At maximum doses, atorvastatin 80 mg has approximately 2-fold higher incidence of drug-related adverse events compared to simvastatin 80 mg (23% vs 12%, p < 0.001), predominantly gastrointestinal symptoms (10% vs 3%, p < 0.001) 6
• Clinically significant ALT elevations occur more frequently with atorvastatin 80 mg (3.8% vs 0.5% with simvastatin 80 mg, p < 0.010), especially in women (6.0% vs 0.6%) 6

Dosing Equivalence for Clinical Practice

When switching between statins, use a 1:2 to 1:4 dose ratio (atorvastatin:simvastatin) to achieve comparable LDL-lowering effects. 1

• Atorvastatin 10 mg ≈ Simvastatin 20-40 mg for LDL reduction 4, 3
• Atorvastatin 20 mg ≈ Simvastatin 40-80 mg for LDL reduction 4
• The American College of Cardiology recognizes simvastatin 40 mg, pravastatin 40 mg, and atorvastatin 10 mg as having solid documentation for cardiovascular risk reduction 5

Drug Interaction Considerations

Simvastatin has more clinically significant drug interactions due to extensive CYP3A4 metabolism, requiring dose limitations with multiple commonly prescribed cardiovascular medications. 5

• Simvastatin requires dose restrictions with amiodarone (≤20 mg), amlodipine (≤20 mg), verapamil (≤10 mg), and diltiazem (≤10 mg) 5, 7
• Atorvastatin, while also metabolized by CYP3A4, has fewer dose restrictions with these agents, though caution is still warranted 5

Clinical Decision Algorithm

Choose atorvastatin when:

• Maximum LDL-lowering is the primary goal 1, 2
• Significant triglyceride reduction is needed 2
• Patient requires aggressive cardiovascular risk reduction (use 80 mg dose) 5
• Patient is on medications that interact with simvastatin (amiodarone, calcium channel blockers) 5

Choose simvastatin when:

• HDL elevation is a priority alongside LDL reduction 1, 6
• Moderate-intensity statin therapy is appropriate (40 mg dose has strong outcomes data) 5
• Cost considerations favor generic simvastatin
• Patient is elderly or frail (avoid 80 mg dose due to myopathy risk) 5