Published Online
on December 31, 2008

A more recent version of this article appeared on January 20, 2009

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Submitted on August 6, 2008
Accepted on October 23, 2008

Cardiovascular Death and Nonfatal Myocardial Infarction in Acute Coronary Syndrome Patients Receiving Coronary Stenting Are Predicted by Residual Platelet Reactivity to ADP Detected by a Point-of-Care Assay. A 12-Month Follow-Up

Rossella Marcucci MD^*, Anna Maria Gori BS, Rita Paniccia BS, Betti Giusti BS, Serafina Valente MD, Cristina Giglioli MD, Piergiovanni Buonamici MD, David Antoniucci MD, Rosanna Abbate MD, and Gian Franco Gensini MD

From the Department of Medical and Surgical Critical Care and the Center for the Study at the Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies (R.M., A.M.G., R.P., B.G., R.A., G.F.G.), University of Florence, Florence, Italy; Department of Heart and Vessels (R.M., A.M.G., R.P., B.G., S.V., C.G., P.B., D.A., R.A., G.F.G.), Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; and Centro S. Maria agli Ulivi (G.F.G.), Fondazione Don Carlo Gnocchi Onlus IRCCS, Impruneta, Florence, Italy.

^* To whom correspondence should be addressed. E-mail: rossella.marcucci{at}unifi.it.

Background—The clinical impact of platelet aggregation assessed by point-of-care assays is unknown. We sought to evaluate whether high residual platelet reactivity (RPR) to ADP during clopidogrel therapy, measured by a point-of-care assay, predicts adverse clinical events in acute coronary syndrome patients undergoing percutaneous coronary intervention.

Methods and Results—We used the VerifyNow P2Y12 assay (Accumetrics Inc, San Diego, Calif) to determine RPR to ADP in 683 patients with acute coronary syndrome undergoing dual-antiplatelet therapy who underwent percutaneous coronary intervention with bare-metal or drug-eluting stent implantation. All patients received a single 600-mg clopidogrel loading dose followed by 75 mg of clopidogrel daily and 100 to 325 mg of aspirin daily. The end points of the study at follow-up of 12 months were cardiovascular death, nonfatal myocardial infarction (MI), and target-vessel revascularization. At a 12-month follow-up, we found 51 ischemic events (24 cardiovascular deaths [3.5%], 27 nonfatal MIs [3.9%]) and 40 target-vessel revascularizations (5.8%). By receiver operating characteristic curve (ROC) analysis, the optimal cutoff value in predicting 12-month cardiovascular death and nonfatal MI was P2Y12 reaction unit values 240. RPR, defined in the presence of P2Y12 reaction unit values above this cutoff, was found to be a significant and independent predictor of cardiovascular death and nonfatal MI in a model that adjusted for cardiovascular risk factors, renal failure, reduced left ventricular ejection fraction, multivessel disease, total stent length, bifurcation lesions, number of lesions treated, type of stent, and use of glycoprotein IIb/IIIa inhibitors (cardiovascular death: hazard ratio 2.55, 95% CI 1.08 to 6.07, P=0.034; nonfatal MI: hazard ratio 3.36, 95% CI 1.49 to 7.58, P=0.004). No significant association was found between high RPR and the risk of target-vessel revascularization.

Conclusions—RPR to ADP with clopidogrel therapy, measured by the point-of-care assay VerifyNow P2Y12, is able to detect acute coronary syndrome patients at risk of 12-month cardiovascular death and nonfatal MI. The optimal cutoff value was identified as being 240 P2Y12 reaction units.

Key words: aspirin • clopidogrel • platelets • bedside testing • acute coronary syndrome

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