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

When to Start Statin Therapy

Initiate statin therapy based on four major clinical categories: established ASCVD (secondary prevention), severe hypercholesterolemia (LDL-C ≥190 mg/dL), diabetes mellitus in adults 40-75 years, and primary prevention based on 10-year ASCVD risk ≥7.5% in adults 40-75 years with LDL-C 70-189 mg/dL. 1

Secondary Prevention (Established ASCVD)

• Start high-intensity statin therapy immediately for all patients with established ASCVD, regardless of age or baseline LDL-C level. 1
• If high-intensity statin is not tolerated, use moderate-intensity statin therapy. 1
• For very high-risk ASCVD patients with LDL-C ≥70 mg/dL despite maximally tolerated statin, consider adding ezetimibe or PCSK9 inhibitor. 1

Severe Hypercholesterolemia

• Initiate maximally tolerated statin therapy (preferably high-intensity) for adults with LDL-C ≥190 mg/dL. 1
• In children and adolescents ≥10 years with LDL-C persistently ≥190 mg/dL or ≥160 mg/dL with clinical familial hypercholesterolemia, initiate statin therapy after 3-6 months of inadequate lifestyle therapy response. 2

Diabetes Mellitus

• Start moderate-intensity statin therapy in all adults 40-75 years with diabetes, regardless of calculated 10-year ASCVD risk. 1
• Consider high-intensity statin therapy for adults with diabetes and multiple ASCVD risk factors, especially those aged 50-70 years. 1

Primary Prevention (No Diabetes, LDL-C 70-189 mg/dL)

High Risk (≥20% 10-year ASCVD risk)

• Initiate high-intensity statin therapy to reduce LDL-C by ≥50%. 1

Intermediate Risk (7.5% to <20% 10-year ASCVD risk)

• Initiate moderate-intensity statin therapy to reduce LDL-C by ≥30%. 1
• Before initiating therapy, engage in clinician-patient risk discussion considering risk-enhancing factors. 1

Risk-Enhancing Factors to Consider:

• Family history of premature ASCVD (men <55 years, women <65 years). 1
• Primary hypercholesterolemia (LDL-C 160-189 mg/dL). 1
• Metabolic syndrome. 1
• Chronic kidney disease. 1
• History of preeclampsia or premature menopause in women. 2
• Chronic inflammatory conditions (rheumatoid arthritis, psoriasis, HIV). 1
• South Asian ancestry. 2
• Persistently elevated triglycerides ≥175 mg/dL. 2

Using CAC Score for Risk Refinement

• When the decision about statin therapy remains uncertain in intermediate-risk or selected borderline-risk adults (5% to <7.5%), measure coronary artery calcium (CAC) score. 1
• If CAC score = 0, it is reasonable to withhold statin therapy and reassess in 5-10 years, unless diabetes, family history of premature CHD, or smoking is present. 1
• If CAC score ≥100 or ≥75th percentile, initiate statin therapy. 1
• In patients with family history of ASCVD, CAC score of zero may impart less short-term benefit from statin therapy. 2

Special Populations

Older Adults (≥75 years)

• Continue statin therapy if already tolerating it in adults ≥75 years with established ASCVD. 1
• For adults ≥75 years without established ASCVD, initiating moderate-intensity statin may be reasonable after discussion of potential benefits and risks. 2, 1
• In adults 76-80 years with LDL-C 70-189 mg/dL, it may be reasonable to measure CAC to reclassify those with CAC score of zero to avoid statin therapy. 2
• Consider stopping statin therapy when functional decline (physical or cognitive), multimorbidity, frailty, or reduced life expectancy limits potential benefits. 2

Children and Adolescents

• Measure fasting or nonfasting lipoprotein profile as early as age 2 years in children with family history of either early CVD or significant hypercholesterolemia to detect familial hypercholesterolemia. 2
• In children with moderate or severe hypercholesterolemia, carry out reverse-cascade screening of family members. 2

Common Pitfalls to Avoid

• Do not delay statin initiation in secondary prevention patients—these patients benefit regardless of baseline LDL-C level. 1
• Do not use low-dose or low-intensity statins when moderate- or high-intensity is indicated—this leaves patients undertreated. 2
• Recognize that approximately 34-58% of statin-treated patients do not achieve therapeutic LDL-C thresholds, often due to inadequate intensity or poor adherence. 3
• Do not routinely monitor liver function tests after statin initiation in asymptomatic patients—this leads to unnecessary testing and potential discontinuation of beneficial therapy. 4
• Avoid stopping statins based on non-specific symptoms without proper evaluation, as placebo-controlled trials show most attributed symptoms are not actually caused by statins. 5

Monitoring After Initiation

• Obtain lipid profile at baseline, 4-12 weeks after initiation or dose change, and every 3-12 months thereafter based on need to assess adherence or safety. 2, 1
• Measure hepatic function only if symptoms suggesting hepatotoxicity arise (unusual fatigue, weakness, loss of appetite, abdominal pain, dark urine, or jaundice). 4