Platelet function and activation markers in primary hypercholesterolemia treated with anti-PCSK9 monoclonal antibody: A 12-month follow-up.
Antibodies, Monoclonal, Humanized
/ adverse effects
Anticholesteremic Agents
/ adverse effects
Biomarkers
/ blood
Blood Platelets
/ drug effects
CD40 Ligand
/ blood
Cholesterol, LDL
/ blood
Female
Humans
Hypercholesterolemia
/ blood
Italy
Male
Middle Aged
P-Selectin
/ blood
PCSK9 Inhibitors
Platelet Aggregation
/ drug effects
Platelet Aggregation Inhibitors
/ adverse effects
Platelet Factor 4
/ blood
Proprotein Convertase 9
/ blood
Prospective Studies
Serine Proteinase Inhibitors
/ adverse effects
Time Factors
Treatment Outcome
Acetyl salicylic acid
Hypercholesterolemia
PCSK9
Platelets
Journal
Nutrition, metabolism, and cardiovascular diseases : NMCD
ISSN: 1590-3729
Titre abrégé: Nutr Metab Cardiovasc Dis
Pays: Netherlands
ID NLM: 9111474
Informations de publication
Date de publication:
10 02 2020
10 02 2020
Historique:
received:
12
06
2019
revised:
14
08
2019
accepted:
09
09
2019
pubmed:
28
10
2019
medline:
25
8
2020
entrez:
27
10
2019
Statut:
ppublish
Résumé
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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31653513
pii: S0939-4753(19)30351-5
doi: 10.1016/j.numecd.2019.09.012
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Anticholesteremic Agents
0
Biomarkers
0
Cholesterol, LDL
0
P-Selectin
0
PCSK9 Inhibitors
0
PF4 protein, human
0
Platelet Aggregation Inhibitors
0
SELP protein, human
0
Serine Proteinase Inhibitors
0
CD40 Ligand
147205-72-9
Platelet Factor 4
37270-94-3
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
evolocumab
LKC0U3A8NJ
alirocumab
PP0SHH6V16
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
282-291Informations de copyright
Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.