Rosuvastatin vs Simvastatin

## Overview

Rosuvastatin and simvastatin differ markedly in potency, metabolism, and safety profile. Rosuvastatin is a fully synthetic, high-potency statin; simvastatin is a semisynthetic prodrug with important dose-related myopathy risks.

## Mechanism of Action

Both competitively inhibit HMG-CoA reductase. Simvastatin requires in vivo hydrolysis to its active beta-hydroxy acid form; rosuvastatin is administered as the active sodium salt.

## Pharmacokinetics

Rosuvastatin has 20% bioavailability, a 19-hour half-life, and undergoes minimal CYP2C9 metabolism. Simvastatin has ~5% bioavailability, a 2–3-hour half-life, and is completely dependent on CYP3A4.

## Pharmacodynamics and Clinical Evidence

Rosuvastatin 10–40 mg reduces LDL-C by 46–55%. Simvastatin is capped at 40 mg for new patients, achieving 26–47% reduction. Rosuvastatin is uniquely supported by METEOR (regression of carotid IMT) and ASTEROID (coronary plaque regression). HORIZON-AMI showed rosuvastatin's benefit in acute MI.

## Safety

The FDA's 2011 label update restricting simvastatin 80 mg was a watershed moment. Rosuvastatin at high doses also carries myopathy risk, particularly in Asian patients, CKD, and those on gemfibrozil. However, rosuvastatin does not carry the specific drug-drug interaction restrictions that make simvastatin 80 mg dangerous.

## Key Takeaways

- Rosuvastatin is significantly more potent per milligram
- Simvastatin 80 mg is largely obsolete; use only in patients already stable on it
- Rosuvastatin is preferred for high-intensity therapy without CYP3A4 interaction concerns