What is the recommended LDL (Low-Density Lipoprotein) goal for individuals taking PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) inhibitors?

LDL Goal for PCSK9 Inhibitors

For patients taking PCSK9 inhibitors, the recommended LDL goal is <1.4 mmol/L (<55 mg/dL) with at least a 50% reduction from baseline.

Risk Stratification and LDL Goals

The LDL goal for patients on PCSK9 inhibitors depends on their cardiovascular risk category:

Very High Risk Patients

• Primary goal: LDL-C <1.4 mmol/L (<55 mg/dL) AND ≥50% reduction from baseline 1
• For patients with recurrent cardiovascular events within 2 years while on maximally tolerated statin therapy, a more aggressive goal of <1.0 mmol/L (<40 mg/dL) may be considered 1

High Risk Patients

• LDL-C <1.8 mmol/L (<70 mg/dL) AND ≥50% reduction from baseline 1

Moderate Risk Patients

• LDL-C <2.6 mmol/L (<100 mg/dL) 1

Treatment Algorithm

1. First-line therapy: High-intensity statin up to the highest tolerated dose 1
2. Second-line therapy: If LDL goal not achieved after 4-6 weeks, add ezetimibe 1
3. Third-line therapy: If LDL goal still not achieved after 4-6 weeks on maximally tolerated statin plus ezetimibe, add PCSK9 inhibitor 1

Real-World Considerations

Despite the potent LDL-lowering effect of PCSK9 inhibitors (approximately 60-65% reduction) 2, 3, real-world data shows:

• Only 55% of patients with established cardiovascular disease achieve LDL-C <70 mg/dL and only 38% achieve LDL-C <55 mg/dL 4
• Factors affecting goal attainment include:
  • Poor medication adherence (only 29% have proportion of days covered ≥80%) 4
  • Baseline LDL-C >190 mg/dL 4
  • Use of PCSK9 inhibitors as monotherapy rather than with statins 4

Common Pitfalls to Avoid

1. Not verifying adequate adherence before concluding treatment failure
2. Discontinuing statins when adding PCSK9 inhibitors (combination therapy is more effective)
3. Not monitoring for LDL goal attainment after initiating PCSK9 inhibitors
4. Using calculated LDL-C in patients with very low LDL-C levels (<70 mg/dL) or elevated triglycerides (direct measurement is more accurate) 1
5. Setting insufficient goals for very high-risk patients (using <70 mg/dL rather than <55 mg/dL)

Special Populations

For patients with familial hypercholesterolemia:

• Without clinical ASCVD: LDL-C <2.6 mmol/L (<100 mg/dL) 1
• With clinical ASCVD or additional risk factors: LDL-C <1.4 mmol/L (<55 mg/dL) 1

Remember that PCSK9 inhibitors are typically reserved for patients who cannot achieve LDL goals despite maximally tolerated statin therapy plus ezetimibe, or for those who are statin-intolerant 1.