Multi-parameter assessment of platelet inhibition and its stability during aspirin and clopidogrel therapy

Thromb Res. 2014 Jul;134(1):96-104. doi: 10.1016/j.thromres.2014.04.023. Epub 2014 Apr 29.


Introduction: Poor response to antiplatelet drugs is associated with adverse outcomes. We assessed platelet inhibition and its stability and tested correlation and agreement between platelet function assays.

Methods: Peripheral blood from 58 patients on both aspirin and clopidogrel who underwent percutaneous coronary intervention (PCI) was collected at hospital discharge (visit-1) and at 30-90 days (visit-2). Platelet function was measured using light transmission aggregometry (LTA-AA and LTA-ADP), VerifyNow® (Aspirin; ARU and P2Y12; PRU), ex vivo TxB2, urinary 11dhTxB2, and VASP (PRI) assays. Data were analyzed as continuous, quartiles and binary. Patients were defined as aspirin poor responder (PR) with ARU ≥ 550, LTA-AA maximum ≥ 20%, TxB2 ≥ 1 ng/mL or 11dhTxB2 ≥ 1,500 pg/mg of creatinine and as clopidogrel PR with PRU ≥ 240, PRU ≥ 208, LTA-ADP maximum ≥ 40%, PRI ≥ 50%, or PRI ≥66%.

Results: Aspirin PR was 3-33% and clopidogrel PR was 10-35% in visit-1. LTA-AA, 11dhTxB2, and all clopidogrel-response measures showed correlation and agreement between visit-1 and visit-2. The highest agreement between two visits was revealed by PRU ≥ 240 and PRI ≥ 66% (PRU-κ=0.7, 95% CI=0.47, 0.93; PRI-κ=0.69, 95% CI=0.42, 0.95, p-values<0.001). Comparison of platelet function assays in a single visit (visit-1) revealed a poor correlation between LTA-AA and 11dhTxB2 assays and no agreement among aspirin-response assays. The highest correlation and agreement were obtained between VerifyNow® P2Y12 and VASP assays (rho=0.7, p-value<0.001 and PRU ≥ 208-PRI-κ=0.41-0.42, 95% CI=0.13, 0.69, p-values<0.001).

Conclusions: Platelet inhibition is stable during aspirin and clopidogrel treatment. Clopidogrel-response assays correlate and agree with each other better than aspirin-response assays.

Keywords: Aspirin; cardiovascular diseases; clopidogrel; drug resistance; percutaneous coronary intervention; platelet function assay.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aspirin / therapeutic use*
  • Clopidogrel
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use


  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Aspirin