Evidence that pre-existent variability in platelet response to ADP accounts for 'clopidogrel resistance' Export

@article{citeulike:4091994, abstract = {Summary. Background: Clopidogrel is a widely used antithrombotic agent that inhibits the platelet P2Y12 adenosine diphosphate (ADP) receptor. There is increasing interest in 'clopidogrel resistance'. Objectives: To determine whether 'clopidogrel resistance' is accounted for by a pre-existent variability in platelet response to ADP. Methods: Platelet response to 20 03BCm ADP was analyzed by four independent whole blood flow cytometric assays: platelet surface activated GPIIb-IIIa, platelet surface P-selectin, monocyte-platelet aggregates and neutrophil-platelet aggregates. In 25 consecutive, non-aspirin-treated healthy subjects, we studied platelet response before and after clopidogrel administration. In addition, we studied the platelet response in 613 consecutive aspirinated patients with or without coronary artery disease (CAD, as determined by angiography) who had or had not been treated with clopidogrel. In these patients, we tested for homogeneity of variance across all durations of clopidogrel exposure and severity of CAD by estimating the 'goodness of fit' of two independent models. Results: In the healthy subjects, pre-clopidogrel response to ADP predicted post-clopidogrel response to ADP. In the patients, clopidogrel, as expected, inhibited the platelet response to ADP. However, irrespective of the duration of clopidogrel administration, the severity of CAD, and the dose of aspirin, clopidogrel did not increase the variance in the platelet response to ADP in any of the four assays of platelet response. Conclusions: These studies provide evidence that 'clopidogrel resistance' is accounted for by a pre-existent variability in platelet response to ADP and this variability is not increased by clopidogrel administration.}, address = {Center for Platelet Function Studies; Divisions of Pediatric Hematology/Oncology, Department of Pediatrics; Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA; Department of Anesthesiology, University of Michigan, Ann Arbor, MI; Division of Clinical Research, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA}, author = {Michelson, A. D. and Linden, M. D. and Furman, M. I. and Li, Y. and Barnard, M. R. and Fox, M. L. and Lau, W. C. and Mclaughlin, T. J. and Frelinger, A. L.}, citeulike-article-id = {4091994}, citeulike-linkout-0 = {http://dx.doi.org/10.1111/j.1538-7836.2006.02234.x}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17002661}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17002661}, citeulike-linkout-3 = {http://www3.interscience.wiley.com/cgi-bin/abstract/117993492/ABSTRACT}, doi = {10.1111/j.1538-7836.2006.02234.x}, journal = {Journal of Thrombosis and Haemostasis}, keywords = {adp, aggregation, agonists, assay, assays, clopidogrel, method, platelet, platelets, resistance, variability}, number = {1}, pages = {75--81}, posted-at = {2009-02-24 10:56:38}, priority = {2}, title = {Evidence that pre-existent variability in platelet response to ADP accounts for 'clopidogrel resistance'}, url = {http://dx.doi.org/10.1111/j.1538-7836.2006.02234.x}, volume = {5}, year = {2007} }

TY - JOUR ID - citeulike:4091994 L3 - citeulike-article-id:4091994 N2 - Summary. Background: Clopidogrel is a widely used antithrombotic agent that inhibits the platelet P2Y12 adenosine diphosphate (ADP) receptor. There is increasing interest in 'clopidogrel resistance'. Objectives: To determine whether 'clopidogrel resistance' is accounted for by a pre-existent variability in platelet response to ADP. Methods: Platelet response to 20 03BCm ADP was analyzed by four independent whole blood flow cytometric assays: platelet surface activated GPIIb-IIIa, platelet surface P-selectin, monocyte-platelet aggregates and neutrophil-platelet aggregates. In 25 consecutive, non-aspirin-treated healthy subjects, we studied platelet response before and after clopidogrel administration. In addition, we studied the platelet response in 613 consecutive aspirinated patients with or without coronary artery disease (CAD, as determined by angiography) who had or had not been treated with clopidogrel. In these patients, we tested for homogeneity of variance across all durations of clopidogrel exposure and severity of CAD by estimating the 'goodness of fit' of two independent models. Results: In the healthy subjects, pre-clopidogrel response to ADP predicted post-clopidogrel response to ADP. In the patients, clopidogrel, as expected, inhibited the platelet response to ADP. However, irrespective of the duration of clopidogrel administration, the severity of CAD, and the dose of aspirin, clopidogrel did not increase the variance in the platelet response to ADP in any of the four assays of platelet response. Conclusions: These studies provide evidence that 'clopidogrel resistance' is accounted for by a pre-existent variability in platelet response to ADP and this variability is not increased by clopidogrel administration. IS - 1 JF - Journal of Thrombosis and Haemostasis AD - Center for Platelet Function Studies; Divisions of Pediatric Hematology/Oncology, Department of Pediatrics; Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA; Department of Anesthesiology, University of Michigan, Ann Arbor, MI; Division of Clinical Research, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA EP - 81 TI - Evidence that pre-existent variability in platelet response to ADP accounts for 'clopidogrel resistance' VL - 5 SP - 75 KW - adp KW - aggregation KW - agonists KW - assay KW - assays KW - clopidogrel KW - method KW - platelet KW - platelets KW - resistance KW - variability AU - Michelson, AD AU - Linden, MD AU - Furman, MI AU - Li, Y AU - Barnard, MR AU - Fox, ML AU - Lau, WC AU - Mclaughlin, TJ AU - Frelinger, AL PY - 2007/// UR - http://dx.doi.org/10.1111/j.1538-7836.2006.02234.x ER -