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. 2022 Mar 22;11(7):1763. doi: 10.3390/jcm11071763

Table 2.

The summary of recent studies addressing the correlations between plasma and leukocyte miRNAs levels and platelet reactivity.

Authors Population Intervention Comparison Outcomes Methods RNA Used for Normalization
Zhang et al. [62] 62 NSTE-ACS pts with troponin negative 300 mg ASA + 300 mg clopidogrel (24 h)
or
100 mg ASA + 75 mg clopidogrel (5 days)
group divided into subgroups compared with each other ↓ plasma miR-223 in PRI low-responders
miR-223 expression correlated with PRI
PRI by VASP phosphorylation flow cytometry
plasma miRNAs analysis by qPCR
human-5 s-rRNA
Chyrchel et al. [50] 21 NSTE-ACS men with an uncomplicated hospital course (75 mg clopidogrel OD or 10 mg prasugrel OD or 90 mg ticagrelor BID)
+ 75–100 mg ASA OD
correlation between plasma miR-223 and PAG
PAG compared between clopidogrel & prasugrel/ticagrelor
↓ PR in pts on prasugrel or ticagrelor compared to clopidogrel
↑ miR-223 with increased DAPT responsiveness
PR measured by MEA
plasma miRNAs analysis by qPCR
prasugrel and ticagrelor combined in miRNAs analysis
miR-16
Kaudewitz et al. [52] 125 ACS pts
30 days after onset of ACS
ASA + clopidogrel/prasugrel/ticagrelor correlations between miRNA levels and platelet functions no correlation between miRNAs and PAG
miR-24, miR-126, miR-191, miR-223 correlated with PRU
miR-126 correlated with PRI
PRU by VerifyNow
and PRI by VASP phosphorylation and PAG by LTA
plasma miRNAs analysis by qPCR
cel-miR-39*
Xie et al. [60] 188 NSTE-ACS pts after elective PCI 100 mg ASA + 75 mg clopidogrel 47 ultra-responders (UR) and 47 non-responders (NR) according to PAG (only 24 and 36 samples analysed, respectively) no difference in hsa-miR-223- 3p between the NR and UR
no significant correlation between miR-223-3p PAG
PAG as a value of electronic impedance (Ω) between the two electrodes immersed in a diluted sample
leukocyte miR-223-3p analysis by qPCR
U6
Tang et al. [59] 115 CAD pts
+ 1199 CAD pts as a prospective cohort
100 mg ASA + 300 mg clopidogrel LD pts divided into 4 subgroups according to ARU and PRU ↑ miR-142 associated with a high risk of MACE
↑ miR-126, miR-142, miR-130a, miR-27a miR-106a in pts resistant to clopidogrel therapy
PRU and ARU by VerifyNow
plasma miRNAs analysis by qPCR
plasma samples mixed from pts of a given subgroup
cel-miR-39
Becker et al. [48] 878 NSTE-ACS pts + 96 pts NSTE-ACS in corroborative cohort 100 mg ASA + (75 mg clopidogrel/10 mg prasugrel) nested case-control study
correlation between PR and miRNA levels
miR-15b-5p, miR-93 and miR-126 associated with PR PRU by VerifyNow or PRI by VASP phosphorylation or Multiplate ADP test assayplasma miRNAs analysis by qPCR and non-targeted miR-Seq analysis 3 most stable endogenous miRNAs

↑—increased, ↓—decreased, ACS—Acute Coronary Syndrome, ARU—aspirin reaction unit, ASA—acetylsalicylic acid, BID—twice daily, CAD—Coronary Artery Disease, DAPT—dual antiplatelet therapy, HPR—high platelet reactivity, HTPR—high on-treatment platelet reactivity, IPA—inhibition of platelet aggregation, LD—loading dose, LPR—low platelet reactivity, LTA—light transmittance aggregometry, LTPR—low on-treatment platelet reactivity, MACE—major adverse cardiovascular events, MD—maintenance dose, MEA—multiple electrode aggregometry, MEA—Multiple electrode aggregometry, miR/miRNA—microRNA, n.d.—no data, NSTE-ACS—non-ST-Elevation Acute Coronary Syndrome, OD—once daily, PAG—ADP-induced platelet aggregation, PCI—percutaneous coronary interventions, PR—platelet reactivity, PRI—platelet reactivity index, PRU—platelet reactivity unit, pts—patients, qPCR—quantitative Polymerase Chain Reaction, STEMI—ST-Elevation Myocardial Infarction, TEG—thromboelastogram, VASP—vasodilator-stimulated phosphoprotein, YO—years old.