Dataset Information

Platelet microRNAs as Potential Novel Biomarkers for Antiplatelet Therapy with P2Y₁₂ Inhibitors and Their Association with Platelet Function.

ABSTRACT:

Introduction

Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy (DAPT). However, the response to treatment can vary considerably. Certain platelet microRNAs (miRs) are suspected to predict DAPT response and influence platelet function. This study aimed to analyze selected miRs' expressions and compare them among patients treated with different P2Y₁₂ inhibitors while assessing their association with platelet activity and turnover parameters.

Materials and methods

We recruited 79 ACS patients post-PCI treated with clopidogrel, ticagrelor, or prasugrel, along with 18 healthy volunteers. Expression levels of miR-126-3p, miR223-3p, miR-21-5p, miR-197-3p, and miR-24-3p, as well as immature platelet fraction (IPF) and ADP-induced platelet reactivity, were measured and compared between groups.

Results

Analyses revealed significantly lower expressions of miR-126-3p, miR-223-3p, miR-21-5p, and miR-197-3p in patients treated with ticagrelor, compared to clopidogrel (fold changes from -1.43 to -1.27, p-values from 0.028 to 0.048). Positive correlations were observed between platelet function and the expressions of miR-223-3p (r = 0.400, p = 0.019) and miR-21-5p (r = 0.423, p = 0.013) in patients treated with potent drugs. Additionally, miR-24-3p (r = 0.411, p = 0.012) and miR-197-3p (r = 0.333, p = 0.044) showed correlations with IPF.

Conclusions

The identified platelet miRs hold potential as biomarkers for antiplatelet therapy. (ClinicalTrials.gov number, NCT06177587).

SUBMITTER: Gumiezna K

PROVIDER: S-EPMC10780110 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Platelet microRNAs as Potential Novel Biomarkers for Antiplatelet Therapy with P2Y<sub>12</sub> Inhibitors and Their Association with Platelet Function.

Gumiężna Karolina K Bednarek Adrian A Sygitowicz Grażyna G Maciejak-Jastrzębska Agata A Baruś Piotr P Hunia Jaromir J Klimczak-Tomaniak Dominika D Kochman Janusz J Grabowski Marcin M Tomaniak Mariusz M

Journal of clinical medicine 20231222 1

<h4>Introduction</h4>Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy (DAPT). However, the response to treatment can vary considerably. Certain platelet microRNAs (miRs) are suspected to predict DAPT response and influence platelet function. This study aimed to analyze selected miRs' expressions and compare them among patients treated with different P2Y<sub>12</sub> inhibitors while assessing their association with ...[more]

PMID: 38202070

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Project description:BackgroundCilostazol combined with P2Y12 receptor inhibitor has been used as a substitute regimen for aspirin-intolerant patients undergoing percutaneous coronary stent implantation on a small scale. Its exact impact on platelet functions and clinical benefits of aspirin-intolerant patients is unknown.HypothesisCilostazol combined with P2Y12 receptor inhibitors could be used as a substitute antiplatelet regimen for aspirin-intolerant patients undergoing percutaneous coronary stent implantation.MethodsIn this multicenter prospective cohort trial, patients undergoing elective percutaneous coronary stent implantation were assigned to the cilostazol group (cilostazol plus P2Y12 receptor inhibitors), based on aspirin intolerance criteria, or the aspirin group (aspirin plus P2Y12 receptor inhibitors). Platelet PAC-1, CD62p, and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) were detected by flow cytometry. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) including all-cause death, acute myocardial infarction, emerging arrhythmia, nonfatal stroke, and heart failure. The secondary endpoints were the Bleeding Academic Research Consortium (BARC) bleeding events.ResultsOne hundred and fifty-four aspirin-intolerant percutaneous coronary stent implantation patients and 154 matched aspirin-tolerant patients from a total of 2059 percutaneous coronary stent implantation patients were enrolled. The relative activation level of PAC-1, CD62p, and platelet reaction index reflected by the VASP-P test were similar in the two groups (p > .05). After 12 months of follow-up, the incidence of all-cause death was 1.9% in the cilostazol group and 1.3% in the aspirin group (risk ratio [RR], 1.500; 95% confidence interval [CI], 0.254-8.852; p = 1.000); the incidence of acute myocardial infarction was 0.6% in the cilostazol group and 1.3% in the aspirin group (RR, 0.500; 95% CI, 0.046-5.457; p = 1.000). No significant difference was seen in other MACCE events, or in any types of BARC bleeding events.ConclusionsCilostazol combined with P2Y12 inhibitors was not inferior to aspirin-based standard therapy and could be used as a reasonable substitute antiplatelet regimen for aspirin-intolerant patients undergoing percutaneous coronary stent implantation, but again with limitations, which required a larger sample and longer follow-up to confirm its efficacy.

Project description:Background: Platelet-derived microvesicles (PMVs), shed from platelet surface membranes, constitute the majority of circulating microvesicles and have been implicated in procoagulant, pro-inflammatory and pro-atherosclerotic effects. Our aim was to compare plasma PMVs numbers in relation to platelet reactivity during dual antiplatelet therapy (DAPT) with various P2Y12 adenosine diphosphate (ADP) receptor antagonists. Methods: In pre-discharge men treated with DAPT for an acute coronary syndrome, plasma PMVs were quantified by flow cytometry on the basis of CD62P (P-selectin) and CD42 (glycoprotein Ib) positivity, putative indices of PMVs release from activated and all platelets, respectively. ADP-induced platelet aggregation was measured by multiple-electrode aggregometry. Results: Clinical characteristics were similar in patients on clopidogrel (n=16), prasugrel (n=10) and ticagrelor (n=12). Platelet reactivity was comparably reduced on ticagrelor or prasugrel versus clopidogrel (p<0.01). Compared to clopidogrel-treated patients, CD42+/CD62P+ PMVs counts were 3-4-fold lower in subjects receiving ticagrelor (p=0.001) or prasugrel (p<0.05), while CD42+ PMVs were significantly reduced on ticagrelor (by about 6-fold, p<0.001), but not prasugrel (p=0.3). CD42+/CD62P+ PMVs numbers correlated positively to the ADP-induced aggregation on clopidogrel (p<0.01) or prasugrel (p<0.05), which was absent in ticagrelor users (p=0.8). CD42+ PMVs counts were unrelated to platelet reactivity (p>0.5). Conclusions: Higher antiplatelet potency of prasugrel and ticagrelor versus clopidogrel is associated with decreased plasma CD42+/CD62P+ PMVs numbers. However, in contrast to thienopyridines, the association of reduced CD42+/CD62P+ PMVs counts with ticagrelor use appears independent of its anti-aggregatory effect. Despite similar platelet-inhibitory activity of ticagrelor and prasugrel, only the treatment with ticagrelor seems associated with lower total PMVs release. Our preliminary findings may suggest a novel pleiotropic effect of ticagrelor extending beyond pure anti-aggregatory properties of the drug.

Dataset Information

Platelet microRNAs as Potential Novel Biomarkers for Antiplatelet Therapy with P2Y₁₂ Inhibitors and Their Association with Platelet Function.

Introduction

Materials and methods

Results

Conclusions

Publications

Platelet microRNAs as Potential Novel Biomarkers for Antiplatelet Therapy with P2Y<sub>12</sub> Inhibitors and Their Association with Platelet Function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Platelet microRNAs as Potential Novel Biomarkers for Antiplatelet Therapy with P2Y12 Inhibitors and Their Association with Platelet Function.

Introduction

Materials and methods

Results

Conclusions

Publications

Platelet microRNAs as Potential Novel Biomarkers for Antiplatelet Therapy with P2Y<sub>12</sub> Inhibitors and Their Association with Platelet Function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Platelet microRNAs as Potential Novel Biomarkers for Antiplatelet Therapy with P2Y₁₂ Inhibitors and Their Association with Platelet Function.