Platelet MicroRNA 365-3p Expression Correlates with High On-treatment Platelet Reactivity in Coronary Artery Disease Patients

PurposeThe expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated.MethodsHealthy subjects (N=20) received no-stent or antiplatelet therapy (as control), and patients (N=155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined.ResultsOf the different treatment regimens, ticagrelor was the most efficacious. At 24h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3% and 90.0%, respectively) and specificity (71.4% and 93.3%) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24h (P0.006) and with miR-365-3p levels 7days following drug administration (P=0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit <85) followed by hyporesponsive (P2Y12 reaction unit 208) and then normoreactive. The normoreactive value was very close to that of controls.ConclusionsOur data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response.Clinical Trial RegistrationNCT02101437