Dual antiplatelet response during PCI: VerifyNow P2Y12 predicts myocardial necrosis and thromboxane B2 generation confirms wide variation in aspirin response

Thromb Res. 2015 Jun;135(6):1140-6. doi: 10.1016/j.thromres.2015.02.021. Epub 2015 Feb 26.

Abstract

Introduction: There remains concern that the antiplatelet effects of aspirin and clopidogrel vary between patients and poor responders may be at increased risk of adverse events. However, the optimal method of measuring aspirin and/or clopidogrel response remains unresolved. We compared three methods of measuring clopidogrel response recommended by a recent consensus statement for the European Society of Cardiology, and investigated a novel approach to measuring aspirin response in patients established on both aspirin and clopidogrel. In addition, we investigated whether any of these assays predict peri-procedural myocardial necrosis following percutaneous coronary intervention (PCI).

Methods: A cross-section of 323 patients attending for PCI was tested for clopidogrel response using VerifyNow P2Y12, VASP Platelet Reactivity Index (VASP-PRI) and whole blood impedance aggregometry (WBPA). Aspirin response was assessed by measuring the residual ability of platelets to generate thromboxane, calculated as the difference between thromboxane B2 levels in serum and plasma, [TxB2]S-P. Peri-procedural myocardial necrosis was determined by a change in troponin I >0.2 μmol/l.

Results: Patients demonstrated wide variation in response to both aspirin and clopidogrel. Correlation between VerifyNow P2Y12 and VASP-PRI was good (r=0.702, p<0.001). Correlation was moderate between WBPA and VerifyNow P2Y12 (r=0.639, p<0.001) and weak for WBPA and VASP-PRI (r=0.353, p<0.001). Only VerifyNow P2Y12 predicted peri-procedural myocardial necrosis.

Conclusions: The three methods of measuring response to clopidogrel identify different patients as poor responders. Poor response to clopidogrel assessed by VerifyNow P2Y12 predicts myocardial necrosis. Measurement of [TxB2]S-P demonstrates a wide variation in aspirin response in patients taking dual antiplatelet therapy.

Keywords: Aspirin; Coronary artery disease; P2Y12 antagonists; Percutaneous coronary intervention; Platelet function tests.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Aspirin / therapeutic use*
  • Blood Platelets / drug effects
  • Clopidogrel
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardium / pathology*
  • Necrosis / pathology*
  • Percutaneous Coronary Intervention / methods*
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Receptors, Purinergic P2Y12 / chemistry*
  • Regression Analysis
  • Thromboxane B2 / chemistry
  • Thromboxane B2 / metabolism*
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Receptors, Purinergic P2Y12
  • Thromboxane B2
  • Clopidogrel
  • Ticlopidine
  • Aspirin