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

Cardiovasc Drugs Ther. 2019 Apr;33(2):129-137. doi: 10.1007/s10557-019-06855-3.

Abstract

Purpose: The 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.

Methods: Healthy 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.

Results: Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h 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 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days 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.

Conclusions: Our data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response.

Clinical trial registration: NCT02101437.

Keywords: Antiplatelet therapy; P2Y12; Platelet reactivity unit; SYNTAX score; miRNA.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aspirin / adverse effects
  • Aspirin / therapeutic use*
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Cilostazol / therapeutic use
  • Clopidogrel / therapeutic use
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / therapy*
  • Drug Resistance* / genetics
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / instrumentation
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Single-Blind Method
  • Stents
  • Taiwan
  • Ticagrelor / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • MIRN365 microRNA, human
  • MicroRNAs
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • Ticagrelor
  • Cilostazol
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT02101437