What is the recommended moderate statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor) treatment for patients at increased risk of cardiovascular events?

Moderate Statin Therapy for Cardiovascular Risk Reduction

For patients at increased risk of cardiovascular events, moderate-intensity statin therapy is recommended to reduce LDL cholesterol by 30-50% from baseline, with specific statin selection based on individual risk factors and comorbidities. 1, 2

Risk Assessment and Statin Indications

• Moderate-intensity statin therapy is indicated for adults at intermediate risk (≥7.5% to <20% 10-year ASCVD risk) with the goal of reducing LDL-C by 30% or more 1
• For all adults aged 40-75 years with diabetes, regardless of estimated 10-year ASCVD risk, moderate-intensity statin therapy is indicated as baseline therapy 1
• In borderline risk patients (5% to <7.5% 10-year ASCVD risk), the presence of risk-enhancing factors may justify initiation of moderate-intensity statin therapy 1
• Risk assessment should incorporate traditional risk factors and risk enhancers specific to diabetes when applicable 1

Moderate-Intensity Statin Options

• Moderate-intensity statins lower LDL cholesterol by approximately 30% to <50% 1, 3
• Specific moderate-intensity statin options include:
  • Atorvastatin 10-20 mg daily 3
  • Rosuvastatin 5-10 mg daily 3
  • Simvastatin 20-40 mg daily 3, 4
  • Pravastatin 40-80 mg daily 5
  • Pitavastatin 1-4 mg daily 2

Treatment Goals and Monitoring

• In intermediate-risk patients, LDL-C levels should be reduced by 30% or more from baseline 1
• For optimal ASCVD risk reduction in high-risk patients (≥20% 10-year ASCVD risk), LDL-C should be reduced by 50% or more 1, 6
• Percent LDL-C reduction provides incremental prognostic value over both statin dose and attained LDL-C levels 6
• Obtain baseline lipid profile before initiating therapy 2, 3
• For patients not on statins, repeat lipid profile every 5 years if under age 40 2

Special Populations

Patients with Diabetes

• For adults 40-75 years with diabetes, moderate-intensity statin therapy is indicated regardless of estimated 10-year ASCVD risk 1
• For patients with diabetes who have multiple ASCVD risk factors, consider high-intensity statin therapy with the aim to reduce LDL-C levels by 50% or more 1
• Metformin should be initiated as first-line therapy along with lifestyle therapies at the time of diabetes diagnosis to improve glycemic control and reduce ASCVD risk 1

Secondary Prevention

• For patients with established ASCVD, high-intensity statin therapy is recommended rather than moderate-intensity therapy 1, 2
• For individuals >75 years of age with clinical ASCVD, moderate-intensity statin therapy should be considered if high-intensity therapy is not tolerated 1

Primary Severe Hypercholesterolemia

• In patients 20-75 years with LDL-C ≥190 mg/dL, maximally tolerated statin therapy is recommended rather than moderate-intensity therapy 1, 7

Managing Statin Intolerance

• For patients who cannot tolerate the intended intensity of statin therapy, use the maximum tolerated dose rather than discontinuing therapy completely 2, 3
• When statin intolerance is encountered, rechallenge with low-dose potent statin and then up-titrate until the cholesterol target has been achieved 8
• If moderate-intensity statin therapy is not tolerated in high-risk patients, consider combining a lower-intensity statin with ezetimibe 7

Common Pitfalls to Avoid

• Low-dose statin therapy is generally not recommended for patients with diabetes as it provides insufficient cardiovascular risk reduction 2
• Failure to escalate to high-intensity statins in appropriate high-risk patients can lead to suboptimal cardiovascular protection 2, 7
• Discontinuing statins due to mild side effects rather than trying dose adjustments or alternative statins may unnecessarily increase cardiovascular risk 2, 8
• At least 75 patients must be treated with statins for one to experience a side effect, while the number needed to treat to prevent one ASCVD event is much lower (between 3 and 61 depending on risk) 8

Comparative Efficacy of Statins

• Rosuvastatin 10-40 mg achieves higher percentages of patients reaching LDL-C <70 mg/dl or ≥50% LDL-C reduction (43.8-79.0%) compared to equal or double milligram doses of atorvastatin (16.1-65.2%) or simvastatin (0-39.7%) 9
• For patients requiring more intensive lipid lowering, high-intensity statins (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) provide greater protection against death or major cardiovascular events than moderate-intensity regimens 5, 7