At what level of cardiovascular risk or low-density lipoprotein cholesterol (LDL-C) should statin therapy be initiated?

When to Start Statin Therapy

Statin therapy should be initiated based on cardiovascular risk assessment, with moderate to high-intensity statins recommended for adults aged 40-75 years with a 10-year ASCVD risk ≥7.5% who have one or more cardiovascular risk factors. 1

Primary Prevention Recommendations

Based on 10-Year ASCVD Risk

The 2018 ACC/AHA guidelines provide a clear framework for statin initiation based on calculated 10-year ASCVD risk:

• High Risk (≥20% 10-year ASCVD risk)

  • Start high-intensity statin therapy 1
  • Goal: LDL-C reduction of ≥50% 1

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

  • Start moderate-intensity statin therapy 1
  • Goal: LDL-C reduction of ≥30% 1
  • Consider high-intensity statin if risk is at the higher end of this range 1

• Borderline Risk (5% to <7.5% 10-year ASCVD risk)

  • Consider moderate-intensity statin if risk-enhancing factors are present 1

Risk-Enhancing Factors

Consider these factors when making decisions about statin therapy, especially in borderline or intermediate-risk patients 1:

• Family history of premature ASCVD
• Persistently elevated LDL-C ≥160 mg/dL
• Metabolic syndrome
• Chronic kidney disease
• History of preeclampsia or premature menopause
• Chronic inflammatory disorders (e.g., rheumatoid arthritis, psoriasis, HIV)
• High-risk ethnic groups (e.g., South Asian)
• Persistent elevations of triglycerides ≥175 mg/dL
• 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

Role of Coronary Artery Calcium (CAC) Scoring

For intermediate-risk or selected borderline-risk adults where the decision about statin therapy remains uncertain, CAC scoring can guide treatment decisions 1:

• CAC score = 0: Reasonable to withhold statin therapy and reassess in 5-10 years (unless patient has diabetes, family history of premature CHD, or is a smoker) 1
• CAC score 1-99: Reasonable to initiate statin therapy, especially in patients ≥55 years of age 1
• CAC score ≥100 or ≥75th percentile: Statin therapy is indicated 1

Special Populations

LDL-C ≥190 mg/dL

• Start high-intensity statin therapy regardless of calculated risk 1
• Goal: LDL-C reduction of ≥50% 1

Diabetes Mellitus (Ages 40-75)

• Start moderate-intensity statin therapy without calculating 10-year ASCVD risk 1
• Consider high-intensity statin for those with multiple risk factors or age 50-75 years 1

Adults Age >75 Years

• Clinical decision-making should consider:
  • Potential benefits and risks
  • Patient preferences
  • Functional status and life expectancy
  • Drug interactions 1

Young Adults (20-39 Years)

• Statin therapy should only be considered when:
  • LDL-C remains >190 mg/dL after 6 months of lifestyle therapy
  • LDL-C remains >160 mg/dL with clinical presentation consistent with familial hypercholesterolemia 2
  • Multiple ASCVD risk factors are present 2

Differences Between Guidelines

There are notable differences between American and European approaches 1:

• American guidelines (ACC/AHA) focus on 10-year ASCVD risk thresholds (7.5% and higher) for initiating statin therapy
• European guidelines (ESC/EAS) emphasize specific LDL-C targets based on risk categories:
  • Very high risk: LDL-C <55 mg/dL
  • High risk: LDL-C <70 mg/dL
  • Moderate risk: LDL-C <100 mg/dL

Common Pitfalls to Avoid

1. Not conducting a clinician-patient risk discussion before starting statin therapy. This should include review of risk factors, potential benefits, side effects, and patient preferences 1

2. Overreliance on calculated risk without considering risk-enhancing factors that may reclassify patients into higher risk categories 1

3. Discontinuing statins due to mild side effects without attempting rechallenge or alternative dosing strategies. Studies show many patients reporting statin-associated symptoms can tolerate statins when rechallenged 3

4. Failing to recognize that most cardiovascular events occur in people at the low to moderate end of population risk distribution 4

5. Not considering CAC scoring in intermediate-risk patients where the decision about statin therapy remains uncertain 1

By following these evidence-based guidelines, clinicians can appropriately identify patients who would benefit most from statin therapy while minimizing unnecessary treatment in those less likely to benefit.