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CLINICAL RESEARCH: ANTIPLATELET THERAPY

Incidence and Clinical Impact of Dual Nonresponsiveness to Aspirin and Clopidogrel in Patients With Drug-Eluting Stents

Anna Maria Gori, MD^_*, Rossella Marcucci, MD^_*, Angela Migliorini, MD, Renato Valenti, MD, Guia Moschi, MD, Rita Paniccia, MD^_*, Piergiovanni Buonamici, MD, Gian Franco Gensini, MD^_*,,, Ruben Vergara, MD, Rosanna Abbate, MD^_* and David Antoniucci, MD^,_*

^_* Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy
Department of Cardiology, Careggi Hospital, Florence, Italy
Center Santa Maria agli Ulivi, Don Carlo Gnocchi Foundation, Istituto di Ricovero e Cura a Carattere Scientifico, Impruneta, Florence, Italy.

Manuscript received February 4, 2008; revised manuscript received May 5, 2008, accepted May 6, 2008.

^_* Reprint requests and correspondence: Dr. David Antoniucci, Division of Cardiology, Careggi Hospital, Viale Pieraccini, I-50134, Florence, Italy. (Email: david.antoniucci{at}virgilio.it).

Objectives: 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.

Key Words: drug-eluting stent • stent thrombosis • nonresponsiveness • clopidogrel

Abbreviations and Acronyms   ADP = adenosine 5'-diphosphate   CI = confidence interval   DES = drug-eluting stent(s)   GP = glycoprotein   HR = hazard ratio

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