Rosuvastatin vs Pravastatin

## Overview

Rosuvastatin and pravastatin share a hydrophilic character but differ fundamentally in potency. Pravastatin's lack of CYP metabolism makes it uniquely safe in polypharmacy patients, while rosuvastatin is used when high-intensity LDL-C reduction is required.

## Mechanism of Action

Both inhibit HMG-CoA reductase competitively. Pravastatin relies on OATP transporters for hepatocyte uptake, contributing to its hepatoselectivity. Rosuvastatin also uses OATP1B1/1B3 for hepatic uptake, making SLCO1B1 polymorphisms relevant to both.

## Pharmacokinetics

Pravastatin: bioavailability ~17%, half-life ~2 h, no CYP metabolism. Rosuvastatin: bioavailability ~20%, half-life 19 h, minimal CYP2C9 metabolism. Both are hydrophilic relative to atorvastatin and simvastatin, potentially explaining their lower CNS and muscle exposure.

## Pharmacodynamics

Rosuvastatin produces 46–55% LDL-C reduction (high-intensity). Pravastatin achieves only 26–34% (moderate-intensity). For aggressive LDL targets (<55 mg/dL in very high-risk patients), rosuvastatin is necessary.

## Clinical Evidence

Pravastatin's CARE and LIPID trials established the secondary prevention benefit of moderate-intensity statin therapy. Rosuvastatin's JUPITER demonstrated primary prevention benefit even in normal-LDL patients with elevated hsCRP. METEOR showed rosuvastatin reduced carotid IMT progression versus placebo.

## Safety

Both are well tolerated. Neither is significantly metabolized by CYP3A4, so neither requires dose adjustment for most CYP3A4 inhibitors. OATP1B1 inhibitors (e.g., cyclosporine, gemfibrozil) can increase exposure of both, warranting caution.

## Key Takeaways

- Rosuvastatin: high-intensity, 19-h half-life, minimal CYP interactions
- Pravastatin: moderate-intensity, very clean drug interaction profile, preferred in transplant
- Both hydrophilic; OATP1B1 polymorphisms relevant to both