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 ,
Jacques Quilici, MD*,
Pierre-Emmanuel Morange, MD, PhD,
Lyassine Nait-Saidi, MD*,
Joseph Carvajal, MD,
Agnès Lehmann,
Marc Lambert, MD*,
Jean-Louis Bonnet, MD* and
Marie-Christine Alessi, MD, PhD,*
* Department of Cardiology, CHU Timone, Marseille, France
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.
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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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D. J. Angiolillo, A. Fernandez-Ortiz, E. Bernardo, F. Alfonso, C. Macaya, T. A. Bass, and M. A. Costa
Variability in Individual Responsiveness to Clopidogrel: Clinical Implications, Management, and Future Perspectives
J. Am. Coll. Cardiol.,
April 10, 2007;
49(14):
1505 - 1516.
[Abstract]
[Full Text]
[PDF]
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D. J. Angiolillo, S. B. Shoemaker, B. Desai, H. Yuan, R. K. Charlton, E. Bernardo, M. M. Zenni, L. A. Guzman, T. A. Bass, and M. A. Costa
Randomized Comparison of a High Clopidogrel Maintenance Dose in Patients With Diabetes Mellitus and Coronary Artery Disease: Results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) Study
Circulation,
February 13, 2007;
115(6):
708 - 716.
[Abstract]
[Full Text]
[PDF]
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M. O'Donoghue and S. D. Wiviott
Clopidogrel Response Variability and Future Therapies: Clopidogrel: Does One Size Fit All?
Circulation,
November 28, 2006;
114(22):
e600 - e606.
[Full Text]
[PDF]
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