Ticagrelor increases endothelial progenitor cell level compared to clopidogrel in acute coronary syndromes: A prospective randomized study

Bonello, Laurent; Frère, Corinne; Cointe, Sylvie; Laine, Marc; Mancini, Julien; Thuny, Franck; Kerbaul, François; Lemesle, Gilles; Paganelli, Franck; Guieu, Régis; Arnaud, Laurent; Dignat-George, Françoise; Sabatier, Florence

doi:10.1016/j.ijcard.2015.03.414

Cited by 37 publications

(30 citation statements)

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“…Preliminary data suggest that ticagrelor interferes with endothelium cells by regulating endothelium calcium signalling and by increasing endothelial progenitor cell levels as compared to clopidogrel. 20,21 This might also explain the higher levels of plasma miRNA-126 under ticagrelor therapy in our analysis.…”

Section: (95%) Uppermentioning

confidence: 87%

Course of platelet miRNAs after cessation of P2Y12 antagonists

Jäger

Stojković

Haller

et al. 2019

Eur J Clin Investigation

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Background: Circulating platelet micro-RNAs (miRNAs) may be used to monitor platelet function during dual antiplatelet therapy (DAPT). Aim of the study was to measure plasma levels of specific miRNAs (miRNA-223, -150, -21 and -126) after physician-driven cessation of chronic P2Y12 inhibition and to study differences in the expression levels of these miRNAs between the different oral P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor, respectively. Design: Patients with coronary artery disease (CAD) on DAPT maintenance dose (including aspirin 100 mg OD, plus clopidogrel 75 mg OD, or prasugrel 10 mg OD, or ticagrelor 90 mg BID) were prospectively enrolled before cessation of the P2Y12inhibitor therapy. MiRNA-223, -150, -21 and -126 were determined at baseline (=last day of P2Y12-inhibitor intake) and 10, 30 and 180 days thereafter. Results: Cessation of P2Y12-inhibitor therapy did not significantly change miRNA levels. However, in ticagrelor-treated patients, miRNA levels were significantly increased at baseline (miRNA-223 and -21), day 10 (miRNA-223, -150, -21, -126) and day 30 (miRNA-223, -150, -21, -126) as compared to prasugrel, and at day 10 (miRNA-150 and -21) and day 30 (miRNA-150) as compared to clopidogrel (all P < 0.05). At day 180, only miRNA-126 levels differed significantly with respect to the P2Y12 inhibitor used (P < 0.05). After adjustment for confounders, choice of P2Y12-inhibitor was the strongest predictor of miRNA levels (P < 0.001), while cessation of P2Y12-inhibitor therapy did not significantly impact miRNA levels. Conclusion: In patients with CAD, ticagrelor intake is associated with increased levels of platelet miRNAs as compared to clopidogrel and prasugrel. Platelet miRNAs are not useful to monitor platelet function after cessation of P2Y12 inhibitors. K E Y W O R D Sdual antiplatelet therapy, micro-RNA, P2Y12 inhibitor, platelet micro-RNA, prasugrel, ticagrelor Note: Therapy group (choice of P2Y12 inhibitor) was the strongest predictor of miRNA expression levels after correction for known and identified baseline differences. Time point did not significantly impact on miRNA levels.

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Section: (95%) Uppermentioning

confidence: 87%

Course of platelet miRNAs after cessation of P2Y12 antagonists

Jäger

Stojković

Haller

et al. 2019

Eur J Clin Investigation

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“…These effects of ticagrelor were dependent on adenosine receptor activation with no effect of clopidogrel in spite of dosing to similar levels of P2Y 12 receptor blockade as ticagrelor (Nanhwan et al, ). In a prospective randomized clinical study, ticagrelor increased the number of circulating endothelial progenitor cell compared with clopidogrel in ACS patients (Bonello et al, ). Finally, in a non‐randomized study, ACS patients on ticagrelor treatment but not on clopidogrel or prasugrel treatment had improved peripheral endothelial function as evaluated with the EndoPAT system (Torngren et al, ).…”

Section: Effects On Vascular Functionmentioning

confidence: 99%

Effects of P2Y₁₂ receptor antagonists beyond platelet inhibition – comparison of ticagrelor with thienopyridines

Nylander

Schulz

2016

British J Pharmacology

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The effect and clinical benefit of P2Y 12 receptor antagonists may not be limited to platelet inhibition and the prevention of arterial thrombus formation. Potential additional effects include reduction of the pro-inflammatory role of activated platelets and effects related to P2Y 12 receptor inhibition on other cells apart from platelets. P2Y 12 receptor antagonists, thienopyridines and ticagrelor, differ in their mode of action being prodrugs instead of direct acting and irreversibly instead of reversibly binding to P2Y 12 . These key differences may provide different potential when it comes to additional effects. In addition to P2Y 12 receptor blockade, ticagrelor is unique in having the only well-documented additional target of inhibition, the equilibrative nucleoside transporter 1. The current review will address the effects of P2Y 12 receptor antagonists beyond platelets and the protection against arterial thrombosis. The discussion will include the potential for thienopyridines and ticagrelor to mediate anti-inflammatory effects, to conserve vascular function, to affect atherosclerosis, to provide cardioprotection and to induce dyspnea. Abbreviations

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“…This editorial constitutes a critical evaluation of recent publications in the setting of ACS patients. Ticagrelor was associated with a significant increase in APC in these clinical studies [9,12]. The mechanism of action seems to be inhibition of adenosine reuptake by red blood cells [8].…”

Section: Resultsmentioning

confidence: 81%

“…This effect of ticagrelor on APC may be responsible for the so-called ''pleiotropic'' properties, particularly at sites of ischaemia and tissue injury, where adenosine is formed. Ticagrelor exerts an additional mode of action -endothelial regeneration [12] -leading to improvement in endothelial function through an increase in APC [9]. Because low EPC concentration and endothelial dysfunction have been associated with a higher rate of adverse events during follow-up, our studies have led to the hypothesis that adenosine-mediated effects of ticagrelor may explain the PLATO mortality data [1].…”

Section: Resultsmentioning

confidence: 92%

“…In a third study [12], we randomly compared the effect of ticagrelor and clopidogrel on EPC concentration in 106 ACS patients undergoing percutaneous coronary intervention. We observed that the use of ticagrelor compared with clopidogrel was associated with a significant increase in the EPC concentration during the first month after an ACS ( Table 1).…”

Section: Effect Of Ticagrelor On Endothelial Progenitor Cell Migrationmentioning

confidence: 99%

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Pleiotropic effects of ticagrelor: Myth or reality?

Mokhtar

Gaubert

Laine

et al. 2016

Archives of Cardiovascular Diseases

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Ticagrelor increases endothelial progenitor cell level compared to clopidogrel in acute coronary syndromes: A prospective randomized study

Cited by 37 publications

References 40 publications

Course of platelet miRNAs after cessation of P2Y12 antagonists

Course of platelet miRNAs after cessation of P2Y12 antagonists

Effects of P2Y₁₂ receptor antagonists beyond platelet inhibition – comparison of ticagrelor with thienopyridines

Pleiotropic effects of ticagrelor: Myth or reality?

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Ticagrelor increases endothelial progenitor cell level compared to clopidogrel in acute coronary syndromes: A prospective randomized study

Cited by 37 publications

References 40 publications

Course of platelet miRNAs after cessation of P2Y12 antagonists

Course of platelet miRNAs after cessation of P2Y12 antagonists

Effects of P2Y12 receptor antagonists beyond platelet inhibition – comparison of ticagrelor with thienopyridines

Pleiotropic effects of ticagrelor: Myth or reality?

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Effects of P2Y₁₂ receptor antagonists beyond platelet inhibition – comparison of ticagrelor with thienopyridines