title: Doubling the clopidogrel dose in patients with reduced responsiveness to the standard dose is associated with a limited effectiveness as evaluated by impedance aggregometry.
abstract: BACKGROUND
  Different methods are available for quantifying platelet function inhibition. Measuring vasodilator-stimulated phosphoprotein (VASP) phosphorylation is currently the most specific method for assessing the clopidogrel effect. The aim of our study was to compare different tests in view of a clinically applicable bedside test. Further, we examined whether doubling the clopidogrel dose to 150mg/d in clopidogrel low-responder would lead to a reduction in platelet reactivity.
  
  
  RESULTS
  ADP-, ADP Hs-, and TRAP-induced platelet aggregation were measured by impedance aggregometry in 100 patients with CAD and 18 healthy controls. Moreover, platelet aggregation was assessed by flow cytometrical detection of VASP-phosphorylation and surface P-selectin in a subgroup of 34 patients and in healthy controls. Another 10 patients with CAD, identified as low-responder, were treated with a clopidogrel dose of 150mg/d. Thereafter, ADP-induced platelet aggregation was assessed by impedance aggregometry. Significant correlations were observed between ADP-induced platelet aggregation assessed by VASP-phosphorylation and by impedance aggregometry. Doubling the dose of clopidogrel to 150mg/d was associated with a reduction of ADP-induced platelet aggregation in only 60% of the patients.
  
  
  CONCLUSIONS
  Impedance aggregometry is a valuable bedside test to assess platelet function inhibition. Doubling the clopidogrel dose is not effective to reduce high on-treatment platelet reactivity in almost half of these patients, pointing to the need of a more powerful platelet inhibitor.
authors.affiliation: Department of Internal Medicine/Cardiology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Stellbaum
authors.forename: Yunus
authors.initials: Y
authors.lastname: Ayral
authors.forename: Andreas
authors.initials: A
authors.lastname: Morguet
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauch
mesh_terms: D000244:Adenosine Diphosphate; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D017097:Electric Impedance; D005260:Female; D005434:Flow Cytometry; D005858:Germany; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010750:Phosphoproteins / Q000097:blood; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D019095:Point-of-Care Systems; D011237:Predictive Value of Tests; D018179:Receptors, Thrombin; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D019007:P-Selectin; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D018179:Receptors, Thrombin; C546937:SELP protein, human; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin