Poor agreement between light transmission aggregometry, Verify Now P2Y₁₂ and vasodilatator-stimulated phosphoprotein for clopidogrel low-response assessment: a potential explanation of negative results of recent randomized trials

Platelets. 2014;25(7):499-505. doi: 10.3109/09537104.2013.840363. Epub 2013 Oct 31.

Abstract

Clopidogrel low response as assessed by several different biological tests correlates with poor prognosis after percutaneous coronary intervention (PCI). However, recent randomized clinical trials (RCT) testing the strategy of individual antiplatelet therapy tailoring based on one sole test have all shown negative results. Poor correlation between the different tests may explain the difficulties of patient selection and identification of "true poor responders" to clopidogrel. In this prospective study, clopidogrel response was assessed in 100 consecutive patients between 18 and 24 hours after a 600 mg clopidogrel loading dose using three different tests: light transmission aggregometry with 10 μmol ADP (LTA, results expressed as platelet aggregation percentage: PAP), Verify Now P2Y12 (VN, results expressed as P2Y12 reaction unit: PRU) and vasodilatator-stimulated phosphoprotein (VASP, results expressed as platelet reactivity index: PRI). Patients under chronic clopidogrel therapy were excluded. The mean PAP, PRU and PRI values were 38.6%, 176.1 PRU and 52.4%, respectively. When clopidogrel response was analyzed as continuous variable, there was a good correlation between the different tests: LTA/VN (R(2 )= 0.642, p < 0.001), LTA/VASP (R(2 )= 0.409, p < 0.001) and VN/VASP (R(2 )= 0.616, p < 0.001). However, when clopidogrel response was analyzed as pre-specified cut-off points to define patients as "poor or good responders" (according to the literature: 50% PAP for LTA, 235 PRU for VN and 50% PRI for VASP), only 47% of the patients were defined as "good" or "poor responders" by the three tests. Altogether, 33% of the patients were defined as "poor responders" by only one test, 20% by two tests and only 16% by the three tests. The correlation between the different tests is good when clopidogrel response is analyzed as continuous variable. Each individual is however rarely (less than 50%) defined as "poor or good responder" by all the three tests when pre-specified cut-off values are used. A sole test might not be sufficient to manage antiplatelet therapy in an individual patient and these results may explain the results of recent RCT showing the lack of benefit of systematic antiplatelet therapy monitoring strategy.

Keywords: Antiplatelet therapy tailoring; Verify Now P2Y12; clopidogrel response; light transmission aggregometry; vasodilatator stimulated phosphoprotein.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Cell Adhesion Molecules / metabolism*
  • Clopidogrel
  • Drug Monitoring / methods
  • Female
  • Humans
  • Male
  • Microfilament Proteins / metabolism*
  • Middle Aged
  • Phosphoproteins / metabolism*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Receptors, Purinergic P2Y12 / metabolism*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Cell Adhesion Molecules
  • Microfilament Proteins
  • P2RY12 protein, human
  • Phosphoproteins
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • vasodilator-stimulated phosphoprotein
  • Clopidogrel
  • Ticlopidine