Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction.
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.
Matetzky
Shlomi
S
Heart Institute, Sheba Medical Center, Tel Hashomer, Israel.
Shenkman
Boris
B
Guetta
Victor
V
Shechter
Michael
M
Beinart
Roy
R
Bienart
Roy
R
Goldenberg
Ilan
I
Novikov
Ilya
I
Pres
Hanna
H
Savion
Naphtali
N
Varon
David
D
Hod
Hanoch
H
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
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