Multiple electrode aggregometry and vasodilator stimulated phosphoprotein-phosphorylation assay in clinical routine for prediction of postprocedural major adverse cardiovascular events

Thromb Haemost. 2011 Aug;106(2):230-9. doi: 10.1160/TH11-02-0077. Epub 2011 May 26.

Abstract

Reduced antiplatelet effect of clopidogrel assessed with multiple electrode aggregometry (MEA) and vasodilator stimulated phosphoprotein-phosphorylation (VASP-P) assay has been proven to predict major adverse cardiovascular events (MACE) after coronary stenting. So far no consecutive registry has evaluated the usefulness of different adenosine diphosphate-based platelet function tests to predict outcome in unselected patients. Hence, our objective was to determine the feasibility of MEA and VASP-P for clinical routine and whether low-response to clopidogrel as determined by MEA and/or the VASP-P assays predicts MACE in a "real-life" population undergoing coronary stenting. Three-hundred consecutive patients were included in this prospective registry. Blood was sampled 6-24 hours after stenting to measure MEA and VASP-P. The use of glycoprotein-IIb/IIIa-blockers limited MEA to 196 measurements. Concerning the VASP-P assay, 300 measurements were achieved. Receiver Operating Characteristics (ROC)-curves of sensitivity and specificity estimates for MACE were plotted for VASP-P assay. The area under the ROC-curve was 0.683 (p=0.014) for the platelet reactivity index (PRI) calculated from median fluorescence intensities (FI) with an optimal cut-off at 60.2% PRI. Patients above 60.2% had a significantly increased risk for MACE at six months follow-up (p=0.007). Estimating the cut-offs for the PRI from mean FI (52%) or from geometric mean FI (56.6%) led to clinically relevant differences. VASP-P assay is feasible for clinical routine to measure clopidogrel effects and to predict post-procedural MACE in unselected patients. With regard to differing cut-offs, exact standardisation of the VASP-P assay is mandatory. The use of GP-IIb/IIIa-blockers prevents MEA testing and limits its usability in unselected patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / drug therapy
  • Acute Coronary Syndrome / therapy
  • Adult
  • Aged
  • Angioplasty, Balloon, Coronary / adverse effects
  • Cell Adhesion Molecules / blood*
  • Clopidogrel
  • Drug Resistance
  • Female
  • Humans
  • Male
  • Microfilament Proteins / blood*
  • Middle Aged
  • Phosphoproteins / blood*
  • Phosphorylation
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Function Tests / methods*
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • Risk Factors
  • Stents / adverse effects
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*

Substances

  • Cell Adhesion Molecules
  • Microfilament Proteins
  • Phosphoproteins
  • Platelet Aggregation Inhibitors
  • vasodilator-stimulated phosphoprotein
  • Clopidogrel
  • Ticlopidine