When should statins (HMG-CoA reductase inhibitors) be prescribed to patients?

When to Give Statins

Statins should be prescribed based on cardiovascular risk stratification and specific high-risk conditions, with the strongest evidence supporting their use in patients with established atherosclerotic cardiovascular disease (ASCVD), diabetes, LDL-C ≥190 mg/dL, and those at high calculated 10-year ASCVD risk (≥7.5%).

Secondary Prevention: Established ASCVD (Strongest Indication)

All patients with established ASCVD should receive high-intensity statin therapy immediately, regardless of baseline LDL-C levels. 1

• Acute coronary syndrome: Initiate or continue high-dose statins early after admission in all ACS patients without contraindication or history of intolerance, regardless of initial LDL-C values 1
• Peripheral arterial disease and carotid artery disease: These are very high-risk conditions requiring statin therapy 1
• History of non-cardioembolic ischemic stroke or TIA: Intensive statin therapy is recommended for secondary stroke prevention 1
• Target: Reduce LDL-C by ≥50% or achieve LDL-C <70 mg/dL (<1.8 mmol/L) 1

Primary Prevention: Risk-Based Approach

Very High-Risk Primary Prevention (LDL-C ≥190 mg/dL)

Patients aged 20-75 years with LDL-C ≥190 mg/dL (≥4.9 mmol/L) should receive maximally tolerated statin therapy. 1

• This includes suspected familial hypercholesterolemia: suspect FH in patients with CHD before age 55 (men) or 60 (women), relatives with premature CVD, tendon xanthomas, or severely elevated LDL-C 1
• FH patients require intense-dose statin, often combined with ezetimibe 1

Diabetes Mellitus

All patients with type 2 diabetes aged 40-75 years should receive at least moderate-intensity statin therapy, regardless of baseline LDL-C. 1

• Type 2 diabetes with CVD or CKD, or age >40 with additional risk factors: Target LDL-C <70 mg/dL (<1.8 mmol/L); use high-intensity statin 1
• Type 2 diabetes with multiple ASCVD risk factors: High-intensity statin is reasonable to reduce LDL-C by ≥50% 1
• Type 2 diabetes without additional risk factors: Target LDL-C <100 mg/dL (<2.6 mmol/L) with moderate-intensity statin 1
• Type 1 diabetes with microalbuminuria or renal disease: LDL-C lowering (≥50%) with statins recommended irrespective of baseline LDL-C 1
• Younger patients (20-39 years) with diabetes and additional ASCVD risk factors: Statin initiation may be reasonable 1

Calculated 10-Year ASCVD Risk ≥7.5%

Adults aged 40-75 years with calculated 10-year ASCVD risk ≥7.5% should be offered statin therapy. 1

• Risk ≥20% (high risk): Initiate high-intensity statin; target LDL-C reduction ≥50% 1
• Risk 10-19.9% (intermediate risk): Initiate moderate-intensity statin; target LDL-C reduction ≥30% or LDL-C <100 mg/dL 1
• Risk 7.5-9.9% (intermediate risk): Moderate-intensity statin recommended after risk discussion 1
• Risk 5-7.4% (borderline risk): Consider statin if risk-enhancing factors present (family history of premature CHD, persistently elevated LDL-C ≥160 mg/dL, metabolic syndrome, chronic kidney disease, chronic inflammatory conditions, premature menopause, high-risk ethnicity) 1

Role of Coronary Artery Calcium (CAC) Scoring

For intermediate-risk (7.5-19.9%) or selected borderline-risk (5-7.4%) patients with uncertain treatment decisions, CAC scoring can guide therapy. 1

• CAC = 0: Reasonable to withhold statin and reassess in 5-10 years (unless diabetes, family history of premature CHD, or cigarette smoking present) 1
• CAC 1-99: Reasonable to initiate statin for patients ≥55 years 1
• CAC ≥100 or ≥75th percentile: Initiate statin therapy 1
• CAC ≥300: Up-classify to high risk 1

Chronic Kidney Disease

Patients with stage 3-5 CKD (not on dialysis) should receive statins or statin/ezetimibe combination. 1

• Stage 3-5 CKD patients are considered high or very high cardiovascular risk 1
• Critical exception: Do not initiate statins in dialysis-dependent CKD patients without established ASCVD 1
• Patients already on statins who start dialysis may continue therapy, especially if ASCVD is present 1

Statin Intensity Selection

High-Intensity Statins (≥50% LDL-C reduction)

• Atorvastatin 40-80 mg daily 1, 2
• Rosuvastatin 20-40 mg daily 1, 2

Moderate-Intensity Statins (30-49% LDL-C reduction)

• Atorvastatin 10-20 mg daily 1
• Rosuvastatin 5-10 mg daily 1, 2
• Simvastatin 20-40 mg daily 1
• Pravastatin 40-80 mg daily 1

Conditions Where Statins Are NOT Recommended

Do not initiate statins in the following situations: 1

• Heart failure without other indications (not harmful, but not beneficial) 1
• Aortic valvular stenosis without CAD and no other indications 1
• Dialysis-dependent CKD without established ASCVD 1
• Autoimmune diseases (universal use not recommended) 1

Special Populations

Asian Patients

• Initiate rosuvastatin at 5 mg once daily; consider risks and benefits if not adequately controlled at doses up to 20 mg daily 2

Severe Renal Impairment (not on hemodialysis)

• Initiate rosuvastatin at 5 mg once daily; do not exceed 10 mg once daily 2

Pregnancy and Women of Childbearing Age

• Avoid lipid-lowering drugs when pregnancy is planned, during pregnancy, and breastfeeding 1
• Stop statin therapy 1-2 months before contemplating pregnancy 1

Age ≥75 Years

• Secondary prevention: Same recommendations as younger patients 1
• Primary prevention: Consider moderate- or high-intensity statin if diabetes, LDL-C 70-189 mg/dL, or high calculated risk; CAC testing can be considered for ages 76-80 if risk uncertainty 1

Monitoring

Assess lipid response 4-12 weeks after initiating or changing statin dose, then annually. 1, 2

• Check liver enzymes and creatine kinase for safety monitoring 3
• Once on stable therapy, lipid panels may be obtained less frequently unless monitoring adherence or efficacy 1

Common Pitfalls to Avoid

• Do not delay statin initiation in ACS patients waiting for lipid levels—start immediately 1
• Do not use gemfibrozil with statins due to significantly higher myopathy risk; fenofibrate is preferred if combination therapy needed 3
• Do not withhold statins in elderly patients with established ASCVD based solely on age 1
• Do not forget to assess for statin intolerance: If side effects occur, try alternative statins or lower doses rather than discontinuing entirely 1