Pablo Corral, Pharmacology Professor at FASTA University, shared a post on X:
“Optimizing PCSK9 inhibitor therapy: Understanding and managing suboptimal LDL-C response in clinical practice
PCSK9 monoclonal antibodies (alirocumab, evolocumab) and the siRNA therapy inclisiran are among the most potent lipid-lowering strategies, achieving ~50–60% LDL-C reduction and significant cardiovascular risk reduction.
Yet, in real-world settings, up to 15% of patients have a suboptimal response (<30% LDL-C reduction).
Key insights from the review:
- Common causes: poor adherence, incorrect injection technique, stopping statin/ezetimibe, biological factors such as high Lp(a) or genetic variants.
- Clinical approach: confirm adherence, optimize injection technique, maintain background therapy, measure plasma PCSK9 if needed.
Switching strategies:
- From mAbs → inclisiran: mechanistically justified; may improve adherence but benefit can be slightly attenuated after prior mAb use.
• From inclisiran → mAbs: less evidence, but possible in selected cases of inadequate response.
Bottom line: Address reversible causes before labeling a patient as a “non-responder” and consider class-switching only when truly necessary.”
Title: Optimizing PCSK9 inhibitor therapy: Understanding and managing suboptimal LDL-C response in clinical practice
Authors: Filippo Giorgio Di Girolamo, Lisa Pellin, Chiara Roni, Gianni Biolo, Gianfranco Sinagra, Enrico Fabris
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