Introduction: Ticagrelor (Ti) has been shown in the PLATO study to significantly reduce the rate of death from vascular causes, myocardial infarction or stroke, without a significant increase in the rate of major bleeding vs Clopidogrel (Cl).
Hypothesis: As Ti has pleiotropic effects, we sought to assess whether the favourable effects of Ti vs. Cl in NSTEMI could be explained , at least in part, by different modulation of circulating MicroRNA (miRNA) and Microparticles (MP)
Methods: we enrolled 56 pts ( 33 male, 23 female), randomized to Ti or Cl , blood samples were taken at first contact with the patients, before loading of Cl or Ti, and subsequently before PCI (at least 3 hours after drug administration), and at 24 and 48h , 1 and 3 months after PCI. Plasma samples and microparticles (MP) were separated by centrifugation steps of pts blood. Plasma RNA was extracted and pooled for microarrays PCR based panel of 90 microRNA analysis. Single plasma RNA of each patient was reverse transcribed for miRNA validation. 10 miRNA were selected for validation. MiRNA expression was normalized for the global mean of each patient. MP count was analyzed by flow-cytometry. MPs were stained with primary antibody conjugated with beads to discriminate between platelet (CD31+/CD42+) and endothelial(CD31+/CD42-) MPs.
Results: MiRNA microarray analysis showed a different modulation of the majority of miRNAs from baseline (before drug loding) and T1(before coronary angiography). In particular, pts receiving Cl presented an upregulation of 95% of all the assessed miRNA, while Ti administration resulted in their down-regulation. Furthermore of the 10 microRNA selected for validation,mir-652-3p was upregulated in patients after 24h from PCI (T2), while mir-155-5p, mir-26b and let-7c were dys-regulated after 48h from PCI (T3).Our preliminary data on MPs have not shown difference between Ti and Cl.
Conclusions: our data suggest that Ticagrelor, when compared with Clopidogrel, may induce a different miRNA modulation that in turn may contribute to explain the different efficacy of Ticagrelor vs Clopidogrel in NSTEMI.