Incidence and clinical impact of dual nonresponsiveness to aspirin and clopidogrel in patients with drug-eluting stents.
OBJECTIVE
This study sought to determine the incidence of aspirin nonresponsiveness in addition to clopidogrel nonresponsiveness and whether this association identifies patients at an increased risk of drug-eluting stent (DES) thrombosis.


BACKGROUND
Nonresponsiveness to clopidogrel is a predictor of DES thrombosis. No prospective data exist about the possible association of dual nonresponsiveness to clopidogrel and aspirin with DES thrombosis.


METHODS
Platelet function was assessed after a loading dose of 600 mg clopidogrel in 746 patients who had successful DES implantation followed by 6-month dual-antiplatelet therapy. Platelet reactivity was assessed by light transmittance aggregometry using adenosine 5'-diphosphate, arachidonic acid, and collagen. The primary end point was definite/probable DES thrombosis at 6 months. The secondary end point was the composite of cardiac mortality and DES thrombosis.


RESULTS
The incidence of dual nonresponsiveness to aspirin and clopidogrel was 6%. Definite/probable DES thrombosis was significantly higher in dual aspirin and clopidogrel nonresponders (11.1%) than in clopidogrel and aspirin responders (2.1%, p < 0.001), isolated clopidogrel nonresponders (2.2%, p < 0.05), or aspirin nonresponders (2.3%, p < 0.05). The incidence of the secondary end point was 4.4% in isolated clopidogrel nonresponders, 2.3% in isolated aspirin nonresponders, and 13.3% in dual aspirin and clopidogrel nonresponders. Dual clopidogrel and aspirin nonresponsiveness was an independent predictor of DES thrombosis (hazard ratio: 3.18, 95% confidence interval: 1.14 to 8.83, p = 0.027) and the composite of cardiac mortality and DES thrombosis (hazard ratio: 2.94, 95% confidence interval: 1.16 to 7.41, p = 0.022).


CONCLUSIONS
Dual nonresponsiveness to aspirin and clopidogrel is a relatively infrequent condition that identifies patients at a very high risk of DES thrombosis or death.
Gori
Anna Maria
AM
Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy.
Marcucci
Rossella
R
Migliorini
Angela
A
Valenti
Renato
R
Moschi
Guia
G
Paniccia
Rita
R
Buonamici
Piergiovanni
P
Gensini
Gian Franco
GF
Vergara
Ruben
R
Abbate
Rosanna
R
Antoniucci
David
D
D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000494:pharmacology*; D000077144:Clopidogrel; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000628:therapy; D018432:Drug Resistance, Multiple; D054855:Drug-Eluting Stents; D005260:Female; D006083:Graft Occlusion, Vascular / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011859:Radiography; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin