What moderate-intensity statin (HMG-CoA reductase inhibitor) is most effective?

From the Guidelines

Rosuvastatin at a dose of 5-10 mg daily is the most effective moderate-intensity statin, as it typically reduces LDL cholesterol by 30-50% and has a high affinity for the HMG-CoA reductase enzyme with favorable pharmacokinetic properties. According to the most recent guidelines from the 2024 standards of care in diabetes 1, rosuvastatin is listed as a moderate-intensity statin option, along with atorvastatin, simvastatin, pravastatin, fluvastatin, and pitavastatin. However, rosuvastatin's potency per milligram and pharmacokinetic properties make it a preferred choice for moderate-intensity statin therapy.

Key Characteristics of Rosuvastatin

• High affinity for the HMG-CoA reductase enzyme
• Favorable pharmacokinetic properties, including longer half-life and reduced susceptibility to metabolism by the cytochrome P450 system
• Effective LDL reduction at lower doses, typically 5-10 mg daily
• Fewer drug interactions compared to other statins

Administration and Monitoring

• Rosuvastatin can be taken at any time of day, with or without food
• Patients should be monitored for potential side effects, such as muscle pain or liver enzyme elevations, typically at 4-12 weeks after initiation and then annually
• Other moderate-intensity statin options, such as atorvastatin 10-20 mg daily, simvastatin 20-40 mg daily, and pravastatin 40-80 mg daily, may be considered based on individual patient needs and characteristics.

Clinical Considerations

• The absolute reductions in ASCVD outcomes are greatest in people with high baseline ASCVD risk, but the overall benefits of statin therapy are convincing across most subgroups, including those with moderate or low risk for ASCVD 1
• The relative benefit of lipid-lowering therapy has been uniform across most subgroups tested, including subgroups that varied with respect to age and other risk factors 1

From the Research

Moderate-Intensity Statin Effectiveness

The effectiveness of moderate-intensity statins can be compared based on their ability to reduce low-density lipoprotein (LDL) cholesterol and non-high density lipoprotein cholesterol (non-HDL-C) levels.

• Atorvastatin, rosuvastatin, and simvastatin are among the most commonly used statins, with varying intensities and effects on lipid profiles 2, 3, 4, 5, 6.
• A network meta-analysis found that rosuvastatin at moderate and high intensity doses, and simvastatin and atorvastatin at high intensity doses, were most effective at reducing non-HDL-C levels in patients with diabetes 4.
• Another study found that atorvastatin, rosuvastatin, and simvastatin were broadly equivalent in terms of their LDL cholesterol-lowering effects, with higher doses resulting in higher reductions in pretreatment LDL and total cholesterol concentrations 5.
• The STELLAR trial compared the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses, and found that rosuvastatin reduced LDL cholesterol by a mean of 8.2% more than atorvastatin, 26% more than pravastatin, and 12% to 18% more than simvastatin 6.

Comparison of Statins

The following statins have been compared in terms of their effectiveness:

• Atorvastatin: effective in reducing LDL cholesterol and non-HDL-C levels, but may have little or no ability to increase high-density lipoprotein (HDL) cholesterol 2, 3, 4, 5.
• Rosuvastatin: found to be more effective than atorvastatin, simvastatin, and pravastatin in reducing LDL cholesterol and non-HDL-C levels 4, 6.
• Simvastatin: broadly equivalent to atorvastatin and rosuvastatin in terms of LDL cholesterol-lowering effects, but may be less effective in reducing non-HDL-C levels 4, 5.
• Pravastatin: less effective than atorvastatin, rosuvastatin, and simvastatin in reducing LDL cholesterol and non-HDL-C levels 2, 4, 6.