Indications for Statin Therapy
Statins are indicated for patients with established atherosclerotic cardiovascular disease (ASCVD), those at high risk for ASCVD, and specific conditions with elevated LDL-C levels to reduce morbidity, mortality, and improve quality of life. 1
Primary Indications for Statin Therapy
1. Established ASCVD (Secondary Prevention)
- High-intensity statin therapy is recommended for all patients ≤75 years with established ASCVD 2, 1
- Moderate-intensity statin therapy is recommended for patients >75 years with established ASCVD 2, 1
- Major ASCVD events qualifying for statin therapy include:
- History of ischemic stroke
- Recent acute coronary syndrome (within past 12 months)
- History of myocardial infarction
- Symptomatic peripheral arterial disease 2
2. Primary Prevention in High-Risk Patients
- Adults with LDL-C ≥190 mg/dL (≥4.9 mmol/L): Maximally tolerated statin therapy without need to calculate 10-year risk 2
- Adults aged 40-75 years with diabetes mellitus: Moderate-intensity statin therapy; high-intensity statin for those with multiple risk factors or aged 50-75 years 2, 1
- Adults aged 40-75 years without diabetes with 10-year ASCVD risk ≥7.5%: Moderate-intensity statin therapy if risk discussion favors statins 2
- Adults aged 40-75 years with 10-year ASCVD risk ≥20%: High-intensity statin therapy 2, 1
3. FDA-Approved Indications
- Reduction of cardiovascular events: MI, stroke, revascularization procedures, and angina in adults with multiple risk factors 3, 4
- LDL-C reduction in:
- Adults with primary hyperlipidemia
- Adults and pediatric patients with heterozygous familial hypercholesterolemia (HeFH)
- Adults and pediatric patients with homozygous familial hypercholesterolemia (HoFH)
- Treatment of:
Risk-Enhancing Factors Supporting Statin Therapy
For patients with borderline (5-7.4%) or intermediate (7.5-19.9%) 10-year ASCVD risk, the following risk-enhancing factors favor statin initiation:
- Family history of premature ASCVD
- Persistently elevated LDL-C ≥160 mg/dL (≥4.1 mmol/L)
- Metabolic syndrome
- Chronic kidney disease
- History of preeclampsia or premature menopause (age <40 years)
- Chronic inflammatory disorders (e.g., rheumatoid arthritis, psoriasis, chronic HIV)
- High-risk ethnic groups (e.g., South Asian)
- Persistent elevations of triglycerides ≥175 mg/dL (≥1.97 mmol/L)
- Elevated apolipoprotein B ≥130 mg/dL
- High-sensitivity C-reactive protein ≥2.0 mg/L
- Ankle-brachial index <0.9
- Elevated lipoprotein(a) ≥50 mg/dL or 125 nmol/L 2
Statin Intensity and LDL-C Targets
High-Intensity Statin Therapy (LDL-C reduction ≥50%)
Moderate-Intensity Statin Therapy (LDL-C reduction 30-49%)
- Atorvastatin 10-20 mg daily
- Rosuvastatin 5-10 mg daily
- Simvastatin 20-40 mg daily
- Pravastatin 40-80 mg daily
- Lovastatin 40 mg daily
- Fluvastatin XL 80 mg daily
- Pitavastatin 1-4 mg daily 2, 1
LDL-C Targets Based on Risk Category
- Very high-risk patients: LDL-C <70 mg/dL (<1.8 mmol/L)
- High-risk patients: LDL-C <100 mg/dL (<2.6 mmol/L) 2, 1
Role of Coronary Artery Calcium (CAC) Score
For adults 40-75 years without diabetes and with LDL-C 70-189 mg/dL at intermediate risk (7.5-19.9%):
- CAC score = 0: May withhold or delay statin therapy (except in smokers, diabetics, or those with family history of premature ASCVD)
- CAC score 1-99: Favors statin therapy, especially in those ≥55 years
- CAC score ≥100 or ≥75th percentile: Statin therapy is indicated 2
Special Considerations
Age-Specific Recommendations
- Age 20-39 years: Consider statin therapy if additional ASCVD risk factors present 1
- Age >75 years: Continue statin therapy if already taking it; consider initiating moderate-intensity statin after weighing benefits and risks 2, 1
Ethnicity Considerations
- Asian patients: Initiate at lower doses due to increased risk of myopathy 1
Safety Considerations
The risk of serious adverse events with statins is low:
- Serious muscle injury (rhabdomyolysis): <0.1%
- Serious hepatotoxicity: ≈0.001%
- Statin-induced newly diagnosed diabetes: ≈0.2% per year 5
Monitoring
- Assess LDL-C 4-12 weeks after statin initiation or dose adjustment
- Repeat every 3-12 months as needed to evaluate response and adherence 2, 1
In patients for whom statin therapy is recommended by current guidelines, the benefits of reducing cardiovascular morbidity and mortality greatly outweigh the risks of adverse effects 5.