title: The influencing factors for clopidogrel-mediated platelet inhibition are assay-dependent.
abstract: BACKGROUND
  Influencing factors for clopidogrel-mediated platelet inhibition have only been evaluated by one or two different test systems in the same population so far. Since previous studies revealed poor correlations between the various platelet function tests, the identification of influencing variables for clopidogrel response may vary from one test system to the next. We therefore investigated whether the influencing factors for clopidogrel-mediated platelet inhibition depend on the used assay.
  
  
  METHODS
  Adenosine diphosphate (ADP)-inducible platelet reactivity was assessed by light transmission aggregometry (LTA), the VerifyNow P2Y12 assay, the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, multiple electrode aggregometry (MEA), and the Impact-R in 288 patients after angioplasty and stenting for cardiovascular disease. By univariate and multivariate regression analyses, we evaluated the impact of age ≥ 75, gender, body mass index (BMI), diabetes, active smoking, hypertension, hyperlipidemia, C-reactive protein, platelet count, creatinine, use of calcium-channel blockers (CCBs), statins, proton pump inhibitors, beta blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers on clopidogrel-mediated platelet inhibition in each test system.
  
  
  RESULTS
  None of the independent influencing variables was consistent through all test systems. Only by LTA and the VerifyNow P2Y12 assay, age ≥ 75 and the use of CCBs were independently associated with higher on-treatment platelet reactivity. Only by the VASP assay and MEA, on-treatment platelet reactivity increased linearly with BMI. Further, only by MEA, residual ADP-inducible platelet reactivity increased linearly with platelet count, whereas an increase in platelet count was independently associated with a decrease in ADP-inducible platelet activation by the Impact-R.
  
  
  CONCLUSIONS
  The influencing factors for platelet reactivity during clopidogrel therapy are assay-dependent.
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. thomas.gremmel@meduniwien.ac.at
authors.forename: Thomas
authors.initials: T
authors.lastname: Gremmel
authors.forename: Sabine
authors.initials: S
authors.lastname: Steiner
authors.forename: Daniela
authors.initials: D
authors.lastname: Seidinger
authors.forename: Renate
authors.initials: R
authors.lastname: Koppensteiner
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Kopp
mesh_terms: D000244:Adenosine Diphosphate; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation; D001241:Aspirin / Q000627:therapeutic use; D001317:Austria; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin