What is the target Low-Density Lipoprotein (LDL) level for primary and secondary prevention of cardiovascular events?

Target LDL Cholesterol Levels for Primary and Secondary Prevention of Cardiovascular Events

For secondary prevention in very high-risk patients with established cardiovascular disease, the target LDL cholesterol should be <70 mg/dL (1.8 mmol/L) or a ≥50% reduction from baseline. For primary prevention in high-risk patients without established cardiovascular disease, the target LDL cholesterol should be <100 mg/dL (2.6 mmol/L). 1

Secondary Prevention (Established Cardiovascular Disease)

• Target LDL-C <70 mg/dL (1.8 mmol/L) or a ≥50% reduction from baseline for patients with established cardiovascular disease 1
• This aggressive target is supported by evidence showing that lowering LDL-C to ≤1.8 mmol/L (70 mg/dL) is associated with the lowest risk of recurrent cardiovascular events 1
• Every 1.0 mmol/L reduction in LDL-C is associated with a corresponding 20-25% reduction in cardiovascular mortality and non-fatal myocardial infarction 1
• Studies show that attainment of LDL-C levels <70 mg/dL by very high-risk patients were independent predictors of reduced cardiovascular events (HR=0.34,95% CI 0.17-0.70) 2

Primary Prevention (No Established Cardiovascular Disease)

• For high-risk individuals without established cardiovascular disease but with risk factors:
  • Target LDL-C <100 mg/dL (2.6 mmol/L) 1
  • For individuals with diabetes mellitus over age 40 with additional risk factors, the primary goal is LDL-C <100 mg/dL 1
  • If LDL-lowering drugs are used, a reduction of at least 30-40% in LDL-C levels should be obtained 1

Special Populations and Considerations

Diabetes Mellitus

• For patients with diabetes and established vascular disease (very high risk): Target LDL-C <70 mg/dL 1
• For patients with diabetes without vascular disease: Target LDL-C <100 mg/dL 1
• If baseline LDL-C is already <100 mg/dL, statin therapy should still be initiated based on risk factor assessment and clinical judgment 1

Chronic Kidney Disease

• Chronic kidney disease (stages 2-5, GFR <90 mL/min/1.73 m²) is considered a coronary heart disease risk-equivalent 1
• LDL-C target should be adapted to the degree of renal failure, generally aiming for <100 mg/dL 1

Familial Hypercholesterolemia

• All patients with familial hypercholesterolemia must be recognized as high-risk patients 1
• Aggressive lipid-lowering therapy is recommended regardless of baseline levels 1

Treatment Approaches to Reach Targets

• Statins are the first-line therapy for LDL-C reduction 1
• For very high-risk patients, maximum tolerated statin therapy is often required to reach the aggressive target of <70 mg/dL 3
• If maximum tolerated statin therapy does not achieve target LDL-C levels:
  • Consider adding ezetimibe (now has stronger recommendation - IIa) 3
  • PCSK9 inhibitors may be considered for patients with familial hypercholesterolemia and patients at very high cardiovascular risk who have markedly elevated LDL-C levels despite maximum tolerated statin and ezetimibe therapy 3

Monitoring and Follow-up

• In adults with established cardiovascular disease, lipid levels should be measured at least annually and more often if needed to achieve goals 1
• In adults under age 40 with low-risk lipid values (LDL-C <100 mg/dL, HDL-C >50 mg/dL, and triglycerides <150 mg/dL), lipid assessments may be repeated every 2 years 1

Common Pitfalls and Caveats

• Despite guideline recommendations, <30% of patients with ASCVD achieve recommended reductions in LDL-C, resulting in preventable cardiovascular events 4
• Low HDL-C remains prevalent across all LDL-C levels but is most prevalent in patients with LDL-C ≤70 mg/dL (79%) 5
• There may be a threshold effect - one study suggests that risk of cardiovascular events decreased monotonically until the LDL-C level was lowered to 70 mg/dL, but when further reduced, the risk was independent of LDL-C 6
• Barriers to achieving LDL-C goals include clinical inertia (failure to initiate/intensify therapy), poor medication adherence, and insurance denials for add-on therapies 4

The evidence strongly supports aggressive LDL-C lowering for secondary prevention to <70 mg/dL or a ≥50% reduction from baseline, and to <100 mg/dL for primary prevention in high-risk individuals. These targets are associated with significant reductions in cardiovascular morbidity and mortality.