Clopidogrel discontinuation and platelet reactivity following coronary stenting.
OBJECTIVE
Antiplatelet therapy with aspirin and clopidogrel is recommended for 1 year after drug-eluting stent (DES) implantation or myocardial infarction. However, the discontinuation of antiplatelet therapy has become an important issue as recent studies have suggested a clustering of ischemic events within 90 days of clopidogrel withdrawal. The objective of this investigation was to explore the hypothesis that there is a transient 'rebound' increase in platelet reactivity within 3 months of clopidogrel discontinuation.


RESULTS
In this prospective study, platelet function was assessed in patients taking aspirin and clopidogrel for at least 1 year following DES implantation. Platelet aggregation was measured using a modification of light transmission aggregometry in response to multiple concentrations of adenosine diphosphate (ADP), epinephrine, arachidonic acid, thrombin receptor activating peptide and collagen. Clopidogrel was stopped and platelet function was reassessed 1 week, 1 month and 3 months later. Thirty-two patients on dual antiplatelet therapy were recruited. Discontinuation of clopidogrel increased platelet aggregation to all agonists, except arachidonic acid. Platelet aggregation in response to ADP (2.5, 5, 10, and 20 μm) and epinephrine (5 and 20 μm) was significantly increased at 1 month compared with 3 months following clopidogrel withdrawal. Thus, a transient period of increased platelet reactivity to both ADP and epinephrine was observed 1 month after clopidogrel discontinuation.


CONCLUSIONS
This study demonstrates a transient increase in platelet reactivity 1 month after clopidogrel withdrawal. This phenomenon may, in part, explain the known clustering of thrombotic events observed after clopidogrel discontinuation. This observation requires confirmation in larger populations.
Mylotte
D
D
Department of Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland, Dublin, Ireland.
Peace
A J
AJ
Tedesco
A T
AT
Mangiacapra
F
F
Dicker
P
P
Kenny
D
D
Foley
D P
DP
D000244:Adenosine Diphosphate; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation*; D016718:Arachidonic Acid; D001241:Aspirin / Q000008:administration & dosage; D000077144:Clopidogrel; D003094:Collagen; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D004837:Epinephrine; D005260:Female; D006801:Humans; D007494:Ireland; D008297:Male; D008875:Middle Aged; D010455:Peptides; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013927:Thrombosis / Q000097:blood / Q000209:etiology; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; D004837:Epinephrine