What are the recommended Low-Density Lipoprotein (LDL) levels and treatment strategies according to Atherosclerotic Cardiovascular Disease (ASCVD) risk stratification?

LDL Targets Based on ASCVD Risk Stratification

For optimal cardiovascular outcomes, LDL cholesterol targets should be determined by ASCVD risk stratification, with very high-risk patients requiring the most aggressive LDL-C reduction to <55 mg/dL and at least 50% reduction from baseline. 1

Risk Categories and LDL-C Targets

Very High Risk

• LDL-C target <55 mg/dL (<1.4 mmol/L) and at least 50% reduction from baseline 1
• Includes patients with:
  • Established ASCVD (clinical or documented on imaging) 1
  • Diabetes with target organ damage or major risk factors 1
  • Severe chronic kidney disease 1
  • SCORE ≥10% 10-year risk of fatal cardiovascular disease 1
  • Familial hypercholesterolemia with ASCVD or major risk factor 1

Extremely High Risk (subset of Very High Risk)

• LDL-C target <40 mg/dL (<1.0 mmol/L) 1, 2
• Includes patients with:
  • Recurrent ASCVD events within 2 years while on maximally tolerated statin therapy 1
  • MI plus previous vascular event in last 2 years 1
  • ACS plus multivessel disease, peripheral arterial disease, or polyvascular disease 1
  • ACS plus familial hypercholesterolemia 1

High Risk

• LDL-C target <70 mg/dL (<1.8 mmol/L) and at least 50% reduction from baseline 1
• Includes patients with:
  • Markedly elevated single risk factors 1
  • SCORE ≥5% to <10% 10-year risk 1
  • Familial hypercholesterolemia without other major risk factors 1

Moderate Risk

• LDL-C target <100 mg/dL (<2.6 mmol/L) 1, 3
• Includes patients with:
  • SCORE ≥1% to <5% 10-year risk 1
  • Younger patients with diabetes without additional risk factors 1

Low Risk

• LDL-C target <116 mg/dL (<3.0 mmol/L) 1
• Includes patients with SCORE <1% 10-year risk 1

Treatment Approach by Risk Category

Very High Risk and Extremely High Risk Patients

1. First-line therapy:

   • High-intensity statin (atorvastatin, rosuvastatin, or pitavastatin) at maximally tolerated dose 1
   • For extremely high-risk patients, consider upfront combination of high-intensity statin + ezetimibe + PCSK9 inhibitor 1

2. If LDL-C target not achieved:

   • Add ezetimibe (class I recommendation) 1
   • If still not at target, add PCSK9 inhibitor (evolocumab, alirocumab, or inclisiran) 1

3. For statin-intolerant patients:

   • Ezetimibe as alternative therapy 1
   • Bempedoic acid 1
   • PCSK9 inhibitors 1

High Risk Patients

1. First-line therapy:

   • High-intensity or moderate-intensity statin at maximally tolerated dose 1, 4

2. If LDL-C target not achieved:

   • Add ezetimibe 1, 4
   • Consider PCSK9 inhibitor if still not at target 1

Moderate and Low Risk Patients

1. First-line therapy:

   • Moderate-intensity statin 1
   • Lifestyle modifications 4

2. If LDL-C target not achieved:

   • Consider increasing statin intensity or adding ezetimibe 1

Special Considerations

Diabetes

• Diabetes alone places patients in a high-risk category 3
• Target LDL-C <100 mg/dL for diabetic patients without cardiac disease 3
• Target LDL-C <55 mg/dL for diabetic patients with established cardiac disease 1, 3

Risk Enhancers to Consider

• Elevated lipoprotein(a) 1
• Elevated high-sensitivity C-reactive protein 1
• Family history of premature ASCVD 1
• Chronic kidney disease 1
• Metabolic syndrome 1
• Inflammatory diseases 1
• South Asian ancestry 1
• Female-specific factors (preeclampsia, premature menopause) 1

Coronary Artery Calcium (CAC) Score

• Use as risk modifier in low or moderate-risk patients 1
• If CAC score >100, reclassify as high risk with LDL-C target <70 mg/dL 1
• If CAC score = 0, statin therapy may be deferred for 5 years in borderline risk patients 1

Common Pitfalls to Avoid

• Failing to recognize that diabetes alone places patients in a high-risk category requiring aggressive lipid management 3
• Not adjusting treatment goals based on updated risk stratification 5
• Underutilization of combination therapy in very high-risk patients 5
• Not considering non-HDL cholesterol or apolipoprotein B as secondary targets in patients with hypertriglyceridemia 1
• Failure to recognize extremely high-risk patients who require more aggressive LDL-C targets 1, 2

Monitoring and Follow-up

• Measure lipid levels 4-6 weeks after initiating or changing therapy 1
• For stable patients, non-fasting lipid profiles can be used for monitoring 1
• When making decisions on changing treatment, use fasting LDL-C, especially in patients with hypertriglyceridemia 1
• Consider direct LDL-C measurement rather than calculated values in patients with elevated triglycerides 3