Platelet function and activation markers in primary hypercholesterolemia treated with anti-PCSK9 monoclonal antibody: A 12-month follow-up.

BACKGROUND AND AIMS: In the association between hypercholesterolemia (HC) and thrombotic risk platelet hyper-reactivity plays an important role. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) to reduce plasma LDL-cholesterol merges as effective therapeutic strategy to prevent cardiovascular (CV) events. Aim of this study was to verify whether a treatment up to 12 months with the monoclonal antibodies (mAbs) anti-PCSK9 influences platelet function in primary HC.

METHODS AND RESULTS: In patients affected by primary HC (n = 24), all on background of statin and 17 on acetyl salicylic acid (ASA), platelet function parameters were evaluated at baseline up to 12 months of treatment with the mAb anti-PCSK9 alirocumab or evolocumab. From baseline, the treatment with anti-PCSK9 mAbs: i) in ASA HC patients, significantly decreased platelet aggregation detected in platelet-rich plasma by light transmission aggregometry and in whole blood Platelet Function Analyzer-100 assay; ii) in all HC patients, significantly decreased platelet membrane expression of CD62P and plasma levels of the in vivo platelet activation markers soluble CD40 Ligand, Platelet Factor-4, and soluble P-Selectin. Furthermore, CD62P expression, and sP-Selectin, PF-4, sCD40L levels significantly correlated with serum PCSK9.

CONCLUSION: Besides markedly lowering LDL-c levels, our results suggest that HC patients benefit from anti-PCSK9 mAb treatment also for reducing platelet reactivity and increasing platelet sensitivity to the inhibitory effects of aspirin. These effects on platelets could play a role in the reduction of CV event incidence in patients treated with PCSK9 inhibitors.