P3689Levels of platelet micro-RNA-223, microRNA-150 and microRNA-21 in patients with coronary artery disease during dual anti platelet therapy and after cessation of P2Y12-inhibitor therapy

Abstract

Background and aim: Platelet micro‐RNA (miRNA) determination has been suggested for monitoring and guiding platelet reactivity in patients with coronary artery disease (CAD) on dual anti‐platelet therapy (DAPT). Aim of this study was to investigate the course of miRNA‐223, miRNA‐150 and miRNA‐21 levels in patients with stable CAD on DAPT (aspirin plus clopidogrel, or prasugrel or ticagrelor) following cessation of the respective P2Y12‐inhibitor, and to compare the course of micro‐RNA levels in different P2Y12‐inhibitors. Methods: In total, 62 patients with stable CAD on DAPT with a planned and physician‐driven cessation of P2Y12 inhibition (clopidogrel: n=19, prasugrel: n=19, ticagrelor: n=24) were prospectively included. All patients were free from ischemic or bleeding events for at least 6 months. Expression levels of miRNA‐ 223, miRNA‐150 and miRNA‐21 were assessed at 4 pre‐specified time points: at baseline (BL, i.e. the last day of P2Y12‐inhibitor intake before cessation), as well as on day 10, day 30 and day 180 following cessation of the P2Y12‐inhibitor, respectively. Result: We found no significant changes in platelet miRNA‐223, miRNA‐150 and miRNA‐21 before and after cessation of the different P2Y12‐inhibitors. However, baseline miRNA‐223 and miRNA‐21 levels were significantly increased in patients taking ticagrelor as compared to prasugrel (p<0.05). Expression levels of miRNA‐ 223, miRNA‐150 and miRNA‐21 were also significantly increased on day 10 and day 30 following therapy with ticagrelor as compared to prasugrel (p<0.05), but no difference was observed on day 180. Significant increase of miRNA‐150 and miRNA‐21 levels was also observed in patients on ticagrelor on day 10 and day 30 as compared to clopidogrel (p<0.05), but no difference in miRNA levels was found between clopidogrel and prasugrel at any time during or after P2Y12‐inhibitor intake. After correction for confounders, choice of P2Y12‐inhibitor was the strongest predictor of miRNA‐223, miRNA‐150 and miRNA‐21 levels on day 10 and day 30 following cessation of DAPT, but not at baseline. Conclusion: No significant changes in platelet‐ miRNA‐223, miRNA‐150 and miRNA‐21 levels were observed after cessation of the different P2Y12‐inhibitors in stable patients following PCI. The significant difference in platelet microRNA expression levels (miRNA‐223, miRNA‐150 and miRNA‐21) between ticagrelor and prasugrel or clopidogrel might indicate a more favorable action of ticagrelor as miRNA‐223 has been shown to be protective for cardiovascular events.