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      Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction.


      Adenosine Diphosphate, antagonists & inhibitors, pharmacology, Aged, Aspirin, administration & dosage, therapeutic use, Biotransformation, Combined Modality Therapy, Coronary Artery Disease, complications, therapy, Coronary Restenosis, epidemiology, prevention & control, Coronary Thrombosis, etiology, Drug Resistance, Drug Therapy, Combination, Epinephrine, Female, Follow-Up Studies, Humans, Male, Middle Aged, Myocardial Infarction, drug therapy, Peptides, Platelet Aggregation, drug effects, Platelet Aggregation Inhibitors, Prodrugs, Prospective Studies, Purinergic P2 Receptor Antagonists, Recurrence, Risk, Smoking, Stents, Ticlopidine, analogs & derivatives, Treatment Outcome

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          Although clopidogrel reduces the risk of cardiovascular episodes after coronary events and stenting, a substantial number of incidents continue to occur. 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). 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.

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