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Platelet function and activation markers in primary hypercholesterolemia treated with anti-PCSK9 monoclonal antibody:
Cristina Barale1, Katia Bonomo2, Chiara Frascaroli2
1Department of Clinical and Biological Sciences of Turin University, Orbassano, Turin, Italy.
Insights
Monoclonal antibodies targeting PCSK9 reduce platelet hyper-reactivity in hypercholesterolemia patients. This anti-platelet effect may contribute to the reduced cardiovascular event risk observed with PCSK9 inhibitors.
Area of Science:
- Cardiology
- Hematology
- Pharmacology
Background:
- Hypercholesterolemia (HC) is linked to increased thrombotic risk, with platelet hyper-reactivity playing a key role.
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective in lowering LDL-cholesterol and preventing cardiovascular events.
Purpose of the Study:
- To investigate the impact of monoclonal antibodies (mAbs) targeting PCSK9 on platelet function in patients with primary hypercholesterolemia over 12 months.
Main Methods:
- Evaluated platelet function in 24 primary hypercholesterolemia patients (some on statins and aspirin) treated with anti-PCSK9 mAbs (alirocumab or evolocumab) for up to 12 months.
- Assessed platelet aggregation, CD62P expression, and plasma levels of soluble CD40 Ligand, Platelet Factor-4, and soluble P-Selectin.
Main Results:
- Treatment with anti-PCSK9 mAbs significantly reduced platelet aggregation in patients also taking aspirin.
- A significant decrease in platelet membrane CD62P expression and plasma levels of in vivo platelet activation markers was observed in all patients.
- Platelet activation marker levels correlated with serum PCSK9 levels.
Conclusions:
- Anti-PCSK9 mAb therapy not only lowers LDL-c but also reduces platelet reactivity in hypercholesterolemia patients.
- These anti-platelet effects may contribute to the observed reduction in cardiovascular event incidence associated with PCSK9 inhibitor treatment.
- The findings suggest enhanced platelet sensitivity to aspirin's inhibitory effects.
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.
