title: Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction.
abstract: BACKGROUND
  Although clopidogrel reduces the risk of cardiovascular episodes after coronary events and stenting, a substantial number of incidents continue to occur.
  
  
  RESULTS
  The antiplatelet effect of clopidogrel was studied prospectively in 60 consecutive patients who underwent primary angioplasty (percutaneous coronary intervention [PCI]) with stenting for acute ST-segment-elevation myocardial infarction (STEMI) to determine whether variability in response to clopidogrel affects clinical outcomes. Patients were stratified into 4 quartiles according to the percentage reduction of ADP-induced platelet aggregation. Although patients in the first quartile were resistant to the effects of clopidogrel (ADP-induced platelet aggregation at day 6, 103+/-8% of baseline), ADP-induced aggregation was reduced to 69+/-3%, 58+/-7%, and 33+/-12% of baseline, respectively, in patients in quartiles 2 through 4 (P<0.01 for all). In addition, epinephrine-induced platelet aggregation and platelet aggregation under flow conditions, assessed by the cone-and-plate(let) analyzer method, were reduced significantly less in the first quartile than in quartiles 2 through 4. Whereas 40% of patients in the first quartile sustained a recurrent cardiovascular event during a 6-month follow-up, only 1 patient (6.7%) in the second quartile and none in the third and fourth quartiles suffered a cardiovascular event (P=0.007).
  
  
  CONCLUSIONS
  Up to 25% of STEMI patients undergoing primary PCI with stenting are resistant to clopidogrel and therefore may be at increased risk for recurrent cardiovascular events.
authors.affiliation: Heart Institute, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Shlomi
authors.initials: S
authors.lastname: Matetzky
authors.forename: Boris
authors.initials: B
authors.lastname: Shenkman
authors.forename: Victor
authors.initials: V
authors.lastname: Guetta
authors.forename: Michael
authors.initials: M
authors.lastname: Shechter
authors.forename: Roy
authors.initials: R
authors.lastname: Beinart
authors.forename: Roy
authors.initials: R
authors.lastname: Bienart
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldenberg
authors.forename: Ilya
authors.initials: I
authors.lastname: Novikov
authors.forename: Hanna
authors.initials: H
authors.lastname: Pres
authors.forename: Naphtali
authors.initials: N
authors.lastname: Savion
authors.forename: David
authors.initials: D
authors.lastname: Varon
authors.forename: Hanoch
authors.initials: H
authors.lastname: Hod
mesh_terms: D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D001711:Biotransformation; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D003324:Coronary Artery Disease / Q000150:complications* / Q000628:therapy; D023903:Coronary Restenosis / Q000453:epidemiology* / Q000517:prevention & control; D003328:Coronary Thrombosis / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000008:administration & dosage / Q000627:therapeutic use; D000077542:Eptifibatide; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control / Q000628:therapy; D010455:Peptides / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011355:Prodrugs / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies; D058919:Purinergic P2 Receptor Antagonists; D012008:Recurrence; D012306:Risk; D012907:Smoking / Q000453:epidemiology; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs; D058919:Purinergic P2 Receptor Antagonists; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000077542:Eptifibatide; D013988:Ticlopidine; D001241:Aspirin; D004837:Epinephrine