title: Association of plasma miR-223 and platelet reactivity in patients with coronary artery disease on dual antiplatelet therapy: A preliminary report.
abstract: Decreased plasma levels of microRNA-223 (miR-223), predominantly of platelet origin, were proposed as a surrogate marker of efficacy of antiplatelet therapy. However, higher on-treatment platelet reactivity was associated with lower plasma miR-223 in patients with coronary artery disease (CAD) on dual antiplatelet therapy (DAPT) including clopidogrel and aspirin. Our aim was to compare plasma miR-223 and platelet reactivity in CAD patients on DAPT with newer P2Y12 antagonists vs. clopidogrel. We studied 21 men with CAD admitted to our centre owing to a non-ST-elevation acute coronary syndrome, and with an uncomplicated hospital course. From the day of admission, the patients were receiving either clopidogrel (n = 11) or prasugrel/ticagrelor (n = 10) in addition to aspirin. Before discharge, miR-223 expression in plasma was estimated by quantitative polymerase chain reaction using the comparative Ct method relative to miR-16 as an endogenous control. Multiple electrode aggregometry was used to assess platelet aggregation in response to adenosine diphosphate (ADP). ADP-induced platelet reactivity was decreased in the patients treated with prasugrel or ticagrelor compared with those on clopidogrel (mean ± SD: 139 ± 71 vs. 313 ± 162 arbitrary units [AU]*min, p = 0.006), due to a more potent antiplatelet activity of the novel P2Y12 antagonists. Consequently, six out of seven patients in the lower tertile of the ADP-induced platelet aggregation were treated with the newer P2Y12 blockers, whereas six out of seven patients in the upper tertile were on clopidogrel. Plasma miR-223 was elevated with decreasing platelet reactivity (Spearman's rho = -0.52; p = 0.015 for trend), being significantly higher in the lower tertile of the ADP-induced platelet aggregation (median [range]: 1.06 [0.25-2.31]) vs. the upper tertile (0.20 [0.13-2.30]) (p = 0.04). In conclusion, our preliminary results argue against the notion of low plasma miR-223 as a marker of platelet responsiveness to DAPT. On the contrary, more potent platelet inhibition associated mainly with newer P2Y12 antagonists appears to coincide with higher miR-223 relative to the subjects with attenuated responsiveness to DAPT.
authors.affiliation: 2nd Department of Cardiology, Jagiellonian University Medical College , Cracow , Poland .
authors.forename: Bernadeta
authors.initials: B
authors.lastname: Chyrchel
authors.forename: Justyna
authors.initials: J
authors.lastname: Totoń-Żurańska
authors.forename: Olga
authors.initials: O
authors.lastname: Kruszelnicka
authors.forename: Michał
authors.initials: M
authors.lastname: Chyrchel
authors.forename: Waldemar
authors.initials: W
authors.lastname: Mielecki
authors.forename: Maria
authors.initials: M
authors.lastname: Kołton-Wróż
authors.forename: Paweł
authors.initials: P
authors.lastname: Wołkow
authors.forename: Andrzej
authors.initials: A
authors.lastname: Surdacki
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001241:Aspirin; D015415:Biomarkers; D000077144:Clopidogrel; D035683:MicroRNAs; D010975:Platelet Aggregation Inhibitors; D013988:Ticlopidine; C525067:MIR223, human
keywords: Clopidogrel; MiR-223; coronary artery disease; platelet reactivity; prasugrel; ticagrelor