Aim. This study was designed to evaluate the relationship between microRNAs (miRNAs), miR-126-3p and miR-223-3p, as new biomarkers of platelet activation, and predicting recurrent thrombotic events after acute myocardial infarction (AMI). Methods and Results. The analysis included 598 patients randomized in the PRAGUE-18 study (ticagrelor vs. prasugrel in AMI). The measurements of miRNAs were performed by using a novel miRNA immunoassay method. The association of miRNAs with the occurrence of the ischemic endpoint (EP) (cardiovascular death, nonfatal MI, or stroke) and bleeding were analyzed. The miR-223-3p level was significantly related to an increased risk of occurrence of the ischemic EP within 30 days (odds ratio (OR) = 15.74, 95% confidence interval (CI): 2.07-119.93, p = 0.008) and one year (OR = 3.18, 95% CI: 1.40-7.19, p = 0.006), respectively. The miR-126-3p to miR-223-3p ratio was related to a decreased risk of occurrence of EP within 30 days (OR = 0.14, 95% CI: 0.03-0.61, p = 0.009) and one year (OR = 0.37, 95% CI: 0.17-0.82, p = 0.014), respectively. MiRNAs were identified as independent predictors of EP even after adjustment for confounding clinical predictors. Adding miR-223-3p and miR-126-3p to miR-223-3p ratios as predictors into the model calculating the ischemic risk significantly increased the predictive accuracy for combined ischemic EP within one year more than using only clinical ischemic risk parameters. No associations between miRNAs and bleeding complications were identified. Conclusion. The miR-223-3p and the miR-126-3p are promising independent predictors of thrombotic events and can be used for ischemic risk stratification after AMI.

1st Department of Internal Medicine Cardioangiology International Clinical Research Center Faculty of Medicine Masaryk University and St Anne's University Hospital 656 91 Brno Czech Republic

BioVendor Laboratory Medicine 621 00 Brno Czech Republic

Cardiocentre 3rd Faculty of Medicine Charles University and University Hospital Kralovske Vinohrady 100 34 Prague Czech Republic

Cardiocentre Department of Cardiology Regional Hospital 370 01 Ceske Budejovice Czech Republic

Department of Anestesiology and Resuscitation University Hospital Kralovske Vinohrady 100 34 Prague Czech Republic

Department of Cardiology University Hospital and Faculty of Medicine in Pilsen Charles University 304 60 Pilsen Czech Republic

Department of Human Pharmacology and Toxicology Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences 621 00 Brno Czech Republic

Department of Internal Medicine and Cardiology University Hospital and Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Institute of Biostatistics and Analyses at the Faculty of Medicine and the Faculty of Science Masaryk University 602 00 Brno Czech Republic

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