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J Am Coll Cardiol, 2006; 48:1339-1345, doi:10.1016/j.jacc.2006.06.049 (Published online 11 September 2006).
© 2006 by the American College of Cardiology Foundation
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FOCUS ISSUE: CARDIAC INTERVENTION

Benefit of a 600-mg Loading Dose of Clopidogrel on Platelet Reactivity and Clinical Outcomes in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome Undergoing Coronary Stenting

Thomas Cuisset, MD*, Corinne Frere, MD{dagger}, Jacques Quilici, MD*, Pierre-Emmanuel Morange, MD, PhD{dagger}, Lyassine Nait-Saidi, MD*, Joseph Carvajal, MD{dagger}, Agnès Lehmann{dagger}, Marc Lambert, MD*, Jean-Louis Bonnet, MD* and Marie-Christine Alessi, MD, PhD{dagger},*

* Department of Cardiology, CHU Timone, Marseille, France
{dagger} INSERM, Faculté de Médecine CHU Timone, Marseille, France

Manuscript received March 14, 2006; revised manuscript received May 30, 2006, accepted June 12, 2006.

* Reprint requests and correspondence: Dr. Marie-Christine Alessi, INSERM, UMR 626 Marseille, F-13385 France. (Email: Marie-Christine.Alessi{at}medecine.univ-mrs.fr).

OBJECTIVES: We analyzed the benefit of a 600-mg clopidogrel loading dose on platelet reactivity and clinical outcomes after stenting for non–ST-segment elevation acute coronary syndrome (NSTE ACS).

BACKGROUND: High post-treatment platelet reactivity (HPPR = adenosine diphosphate 10 µmol · l–1 [ADP]–induced platelet aggregation >70%) is a marker for low responders to dual antiplatelet therapy with increased risk of recurrent cardiovascular (CV) events after stenting for NSTE ACS.

METHODS: A total of 292 consecutive NSTE ACS patients undergoing coronary stenting were included and randomly received a 300-mg (n = 146) or 600-mg (n = 146) loading dose of clopidogrel at least 12 h before percutaneous coronary intervention. A single post-treatment blood sample was obtained before percutaneous coronary intervention to analyze maximal intensity of ADP-induced platelet aggregation and platelet surface expression of P-selectin. One-month follow-up CV events were recorded.

RESULTS: The ADP-induced platelet aggregation and expression of P-selectin were significantly lower in patients receiving 600 mg than in those receiving 300 mg (mean ± SD: 50 ± 19% vs. 61 ± 16%, p < 0.0001 and 0.38 ± 0.24 arbitrary units vs. 0.60 ± 0.40 arbitrary units; p < 0.0001 respectively). Persistence of HPPR was less common in patients receiving 600 mg than in those receiving 300 mg (15 vs. 25%, p = 0.03). During the 1-month follow-up, 18 CV events (12%) occurred in the 300-mg group versus 7 (5%) in the 600-mg group (p = 0.02); this difference was not affected by adjustment for conventional CV risk factors (p = 0.035).

CONCLUSIONS: In NSTE ACS patients undergoing coronary stenting, a 600-mg loading dose of clopidogrel shows its benefit on platelet reactivity and clinical prognosis.

Abbreviations and Acronyms
  ADP = adenosine diphosphate
  CREDO = Clopidogrel for Reduction of Events During Observation
  CV = cardiovascular
  HPPR = high post-treatment platelet reactivity
  NSTE ACS = non–ST-segment elevation acute coronary syndrome
  PCI = percutaneous coronary intervention
  PCI-CURE = Percutaneous Coronary Intervention-Clopidogrel in Unstable Angina to Prevent Recurrent Events
  PRP = platelet-rich plasma
  ST = stent thrombosis




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