When should statin (HMG-CoA reductase inhibitor) therapy be initiated?

When to Start Statin Therapy

Statin therapy should be initiated based on cardiovascular risk assessment, with specific recommendations for different age groups and risk factors, including moderate-intensity statins for adults 40-75 years with diabetes or 10-year ASCVD risk ≥7.5%, and high-intensity statins for those with established ASCVD or at higher risk.

Primary Prevention (No Existing ASCVD)

Adults 40-75 Years Old

• For adults 40-75 years with diabetes: Initiate moderate-intensity statin therapy regardless of calculated 10-year ASCVD risk 1
• For adults 40-75 years with 10-year ASCVD risk ≥7.5% to <20%: Initiate moderate-intensity statin therapy to reduce LDL-C by 30% or more 1
• For adults 40-75 years with 10-year ASCVD risk ≥20%: Initiate high-intensity statin therapy to reduce LDL-C by 50% or more 1
• For adults with diabetes and multiple ASCVD risk factors: Consider high-intensity statin therapy to reduce LDL-C by 50% or more 1
• For adults with borderline risk (5% to <7.5% 10-year risk): Selectively offer statin therapy if risk-enhancing factors are present 1

Adults 20-39 Years Old

• For adults 20-39 years with diabetes and additional ASCVD risk factors: Consider initiating statin therapy in addition to lifestyle therapy 1
• For adults 20-75 years with LDL-C ≥190 mg/dL: Initiate maximally tolerated statin therapy (preferably high-intensity) 1

Adults >75 Years Old

• For adults >75 years already on statin therapy: Continue statin treatment if tolerated 1
• For adults >75 years not on statin therapy: Consider initiating statin therapy after discussion of potential benefits and risks 1
• Evidence is insufficient to determine the balance of benefits and harms in adults ≥76 years with no history of CVD 2

Secondary Prevention (Established ASCVD)

• For patients of all ages with ASCVD: Initiate or continue high-intensity statin therapy 1
• For patients with ASCVD unable to tolerate high-intensity statin: Use moderate-intensity statin as the second option 1
• For patients with ASCVD considered very high risk: If LDL-C remains ≥70 mg/dL on maximally tolerated statin dose, consider adding ezetimibe or PCSK9 inhibitor 1

Special Populations

Chronic Kidney Disease

• For patients with CKD ≥50 years: Initiate statin therapy 1
• For patients with CKD and known CAD, diabetes, prior ischemic stroke, or 10-year CVD risk >10%: Initiate statin therapy 1

Contraindications

• Pregnancy: Statin therapy is contraindicated 1, 3, 4
• Breastfeeding: Not recommended due to potential for serious adverse reactions in breastfed infants 3, 4

Monitoring After Initiation

• Obtain lipid profile at initiation of statin therapy, 4-12 weeks after initiation or dose change, and annually thereafter 1
• Monitor for adverse effects, particularly muscle symptoms, which occur in <0.1% of patients with serious muscle injury 5
• For patients who discontinue due to subjective complaints (approximately 10% in clinical practice), consider rechallenge with a different statin 5

Common Pitfalls to Avoid

• Undertreatment: Despite guidelines, many high-risk patients remain untreated or undertreated with statins 6, 7, 8
• Discontinuation: Median time to statin discontinuation is approximately 15 months, with higher persistence among those on high-intensity regimens 6
• Failure to escalate therapy: Only 29.8% of patients who discontinue one statin try at least 2 different statins 7
• Age bias: Older adults may be undertreated despite potential benefits 1
• Overreliance on risk calculators: Risk calculators may not capture all relevant factors; consider additional risk enhancers when making treatment decisions 1

By following these evidence-based recommendations for statin initiation, clinicians can significantly reduce cardiovascular morbidity and mortality in appropriate patient populations.