Which statins (HMG-CoA reductase inhibitors) increase High-Density Lipoprotein (HDL) cholesterol?

Statins and HDL Cholesterol Elevation

All statins modestly increase HDL cholesterol levels, but rosuvastatin, simvastatin, and pitavastatin demonstrate superior HDL-raising effects compared to atorvastatin, with rosuvastatin and pitavastatin showing the most consistent and pronounced increases. 1, 2, 3

HDL-Raising Efficacy by Statin

Most Effective HDL-Raising Statins

• Rosuvastatin increases HDL-C by approximately 8-10% at standard doses (10-20 mg), with consistent effects across all intensity levels 4, 3, 5
• Pitavastatin increases HDL-C by 3-10% across its dose range (1-4 mg), with the unique advantage of enhancing HDL functionality including cholesterol efflux capacity and antioxidative properties 2, 6
• Simvastatin increases HDL-C by approximately 8% at therapeutic doses, with effects comparable to rosuvastatin 7, 5

Moderate HDL-Raising Statins

• Pravastatin and lovastatin produce modest HDL-C increases but are less potent than rosuvastatin or pitavastatin 1
• Fluvastatin demonstrates minimal HDL-raising effects 1

Least Effective for HDL Elevation

• Atorvastatin shows an inverse dose-response relationship for HDL-C elevation—higher doses actually produce smaller HDL-C increases, making it the least favorable choice when HDL elevation is a therapeutic goal 3, 5

Important Clinical Considerations

Dose-Response Relationships

• Rosuvastatin and simvastatin demonstrate positive dose-response relationships for HDL-C elevation (higher doses produce greater HDL increases) 5
• Atorvastatin uniquely shows an inverse relationship—HDL-C increases are smaller at higher doses (80 mg produces less HDL elevation than 10-20 mg) 5
• Pitavastatin maintains consistent HDL-raising effects across its entire dose range 2

Predictors of HDL Response

• Baseline HDL-C levels: Patients with lower baseline HDL-C (<40 mg/dL in men, <50 mg/dL in women) experience greater percentage increases in HDL-C with statin therapy 3, 5
• Baseline triglyceride levels: Higher baseline triglycerides predict greater HDL-C increases with statin therapy 5
• Diabetes status: Diabetic patients demonstrate enhanced HDL-C responses to statins compared to non-diabetic patients 5

HDL Changes Are Independent of LDL Reduction

• The magnitude of HDL-C increase shows no correlation with the degree of LDL-C reduction (correlation coefficient = 0.005), indicating these are independent mechanisms 5
• This means you cannot predict HDL response based on LDL response, and vice versa 5

Clinical Context: When HDL Elevation Matters

Statins Are Not First-Line for Isolated Low HDL

• Statins are primarily LDL-lowering agents—their HDL-raising effects are modest (typically 5-10%) and should not be the primary reason for statin selection 1
• For patients requiring significant HDL elevation, fibrates (gemfibrozil, fenofibrate) or niacin are more effective, though these lack the cardiovascular outcomes data that statins possess 1

Combined Dyslipidemia Strategy

• In patients with both elevated LDL-C and low HDL-C, rosuvastatin or pitavastatin offer the advantage of addressing both abnormalities simultaneously 2, 3
• High-dose statins (particularly rosuvastatin 20-40 mg) can reduce triglycerides by 10-30%, which indirectly supports HDL-C elevation 4, 2

Combination Therapy Considerations

• When statin monotherapy fails to adequately raise HDL-C, combination with fenofibrate is more effective than gemfibrozil (lower myopathy risk) 1
• Niacin combined with statins produces the largest HDL-C increases but requires caution in diabetic patients due to glycemic effects 1

Common Pitfalls to Avoid

• Do not use high-dose atorvastatin (80 mg) if HDL elevation is a goal—it produces less HDL increase than moderate doses 5
• Do not assume all statins have equivalent HDL effects—there is significant heterogeneity among statins 8, 5
• Do not rely solely on HDL-C elevation for cardiovascular risk reduction—LDL-C lowering remains the primary evidence-based target for cardiovascular outcomes 1
• Do not overlook lifestyle modifications—weight loss, increased physical activity, and smoking cessation can increase HDL-C and should be implemented alongside pharmacotherapy 1