This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moshfegh, K. Articles by Meyer, B. J. Search for Related Content PubMed PubMed Citation Articles by Moshfegh, K. Articles by Meyer, B. J.

PLATELET INHIBITOR

Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy

^a Department of Cardiology and Thrombosis Research, University Hospital Bern, Bern, Switzerland
^* Department of Hematology, University Hospital Bern, Bern, Switzerland

Manuscript received October 21, 1999; revised manuscript received January 21, 2000, accepted April 11, 2000.

Reprint requests and correspondence: Dr. Beat J. Meyer, Department of Cardiology and Thrombosis Research, University Hospital, Inselspital, Freiburgstrasse 7, CH-3010 Bern, Switzerland
bmeyer{at}insel.ch

OBJECTIVES

We sought to compare the inhibitory effects of the combination of two doses of aspirin plus clopidogrel with either drug alone on platelet aggregation and activation.

BACKGROUND

Enhanced platelet inhibitory effects of clopidogrel by aspirin on platelet aggregation and activation are suggested by experimental studies but have not been shown in humans.

METHODS

The effects of clopidogrel 75 mg or aspirin 100 (300) mg on platelet aggregation and activation by flow cytometry after stimulation with various agonists were determined in 30 patients with a past history of myocardial infarction.

RESULTS

Clopidogrel alone or in combination with aspirin markedly inhibited adenosine diphosphate (ADP)-mediated platelet aggregation compared with monotherapy with aspirin (24.6 ± 3.3% or 26.6 ± 2.7% vs. 44.7 ± 2.9%; p < 0.001). Combined treatment significantly inhibited collagen-induced aggregation compared with aspirin and clopidogrel (16.4 ± 2.4%, 36.5 ± 4.2% and 59.3 ± 5.1%, respectively; p < 0.001) and resulted in considerable inhibition of aggregation induced by thrombin receptor agonist peptide (TRAP, p < 0.03). Clopidogrel with or without aspirin significantly suppressed expression of platelet activation markers CD 62p, CD 63 and PAC-1 after stimulation with ADP or thrombin (p < 0.001). In addition, the combined treatment was more effective than either agent alone after activation with low dose thrombin (p < 0.05). Both doses of aspirin equally potentiated the platelet inhibitory effects of clopidogrel.

CONCLUSIONS

In this prospective clinical ex vivo platelet study, clopidogrel was more effective than aspirin in inhibiting ADP-mediated platelet aggregation and activation. Clopidogrel in combination with aspirin showed synergistic inhibitory effects after stimulation with collagen and thrombin compared with monotherapies. Thus, this dual antiplatelet treatment strategy deserves further evaluation in clinical trials for secondary prevention of acute myocardial infarction or unstable angina.

Abbreviations and Acronyms   ADP = adenosine diphosphate   GP IIb/IIIa = glycoprotein IIb/IIIa   MI = myocardial infarction   PBS = phosphate buffered saline   PPP = platelet-poor plasma   PRP = platelet-rich plasma   TRAP = thrombin receptor agonist peptide

This article has been cited by other articles:

				G. M. De Ferrari, A. Sanzo, A. Bertoletti, G. Specchia, E. Vanoli, and P. J. Schwartz Baroreflex Sensitivity Predicts Long-Term Cardiovascular Mortality After Myocardial Infarction Even in Patients With Preserved Left Ventricular Function J. Am. Coll. Cardiol., December 11, 2007; 50(24): 2285 - 2290. [Abstract] [Full Text] [PDF]

				G. E. Cooke, Y. Liu-Stratton, A. K. Ferketich, M. L. Moeschberger, D. J. Frid, R. D. Magorien, P. F. Bray, P. F. Binkley, and P. J. Goldschmidt-Clermont Effect of Platelet Antigen Polymorphism on Platelet Inhibition by Aspirin, Clopidogrel, or Their Combination J. Am. Coll. Cardiol., February 7, 2006; 47(3): 541 - 546. [Abstract] [Full Text] [PDF]

				B. Labarthe, P. Theroux, M. Angioi, and M. Ghitescu Matching the Evaluation of the Clinical Efficacy of Clopidogrel to Platelet Function Tests Relevant to the Biological Properties of the Drug J. Am. Coll. Cardiol., August 16, 2005; 46(4): 638 - 645. [Abstract] [Full Text] [PDF]

				D. J. Angiolillo, A. Fernandez-Ortiz, E. Bernardo, C. Ramirez, M. Sabate, P. Jimenez-Quevedo, R. Hernandez, R. Moreno, J. Escaned, F. Alfonso, et al. Platelet Function Profiles in Patients With Type 2 Diabetes and Coronary Artery Disease on Combined Aspirin and Clopidogrel Treatment Diabetes, August 1, 2005; 54(8): 2430 - 2435. [Abstract] [Full Text] [PDF]

				L. Englberger, B. Faeh, P. A. Berdat, F. Eberli, B. Meier, and T. Carrel Impact of clopidogrel in coronary artery bypass grafting Eur. J. Cardiothorac. Surg., July 1, 2004; 26(1): 96 - 101. [Abstract] [Full Text] [PDF]

				S. Matetzky, B. Shenkman, V. Guetta, M. Shechter, R. Bienart, I. Goldenberg, I. Novikov, H. Pres, N. Savion, D. Varon, et al. Clopidogrel Resistance Is Associated With Increased Risk of Recurrent Atherothrombotic Events in Patients With Acute Myocardial Infarction Circulation, June 29, 2004; 109(25): 3171 - 3175. [Abstract] [Full Text] [PDF]

				Z. Xiao and P. Theroux Clopidogrel inhibits platelet-leukocyte interactions and thrombin receptor agonist peptide-induced platelet activation in patients with an acute coronary syndrome J. Am. Coll. Cardiol., June 2, 2004; 43(11): 1982 - 1988. [Abstract] [Full Text] [PDF]

				S. Pothula, V. T. Sanchala, B. Nagappala, and M. A. Inchiosa Jr. The Effect of Preoperative Antiplatelet/Anticoagulant Prophylaxis on Postoperative Blood Loss in Cardiac Surgery Anesth. Analg., January 1, 2004; 98(1): 4 - 10. [Abstract] [Full Text] [PDF]

				A. D. Blann, S. K. Nadar, and G. Y.H. Lip The adhesion molecule P-selectin and cardiovascular disease Eur. Heart J., December 2, 2003; 24(24): 2166 - 2179. [Abstract] [Full Text] [PDF]

				H. Jneid, D. L. Bhatt, R. Corti, J. J. Badimon, V. Fuster, and G. S. Francis Aspirin and Clopidogrel in Acute Coronary Syndromes: Therapeutic Insights From the CURE Study Arch Intern Med, May 26, 2003; 163(10): 1145 - 1153. [Abstract] [Full Text] [PDF]

				A. J. Grau, S. Reiners, C. Lichy, F. Buggle, A. Ruf, and B. Jilma Platelet Function Under Aspirin, Clopidogrel, and Both After Ischemic Stroke: A Case-Crossover Study * Synergistic Antiplatelet Effects of Clopidogrel and Aspirin Detected With the PFA-100 in Stroke Patients Stroke, April 1, 2003; 34(4): 849 - 854. [Abstract] [Full Text] [PDF]

				E. J. Topol A guide to therapeutic decision-making in patients with non-ST-segment elevation acute coronary syndromes J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 123S - 129S. [Abstract] [Full Text] [PDF]

				J.W. Eikelboom, J.I. Weitz, A. Budaj, F. Zhao, I. Copland, P. Maciejewski, M. Johnston, and S. Yusuf Clopidogrel does not suppress blood markers of coagulation activation in aspirin-treated patients with non-ST-elevation acute coronary syndromes Eur. Heart J., November 2, 2002; 23(22): 1771 - 1779. [Abstract] [Full Text] [PDF]

				V. M Oh Warfarin combined with low dose aspirin in myocardial infarction did not provide clinical benefit beyond that of aspirin alone Evid. Based Med., September 1, 2002; 7(5): 140 - 140. [Full Text] [PDF]

				R. H. Hongo, J. Ley, S. E. Dick, and R. R. Yee The effect of clopidogrel incombination with aspirin whengiven before coronary artery bypass grafting J. Am. Coll. Cardiol., July 17, 2002; 40(2): 231 - 237. [Abstract] [Full Text] [PDF]

				D. L. Bhatt and E. J. Topol Need to Test the Arterial Inflammation Hypothesis Circulation, July 2, 2002; 106(1): 136 - 140. [Full Text] [PDF]

				H. Mehta and B. J. Meyer r-Hirudin for percutaneous coronary interventions--time to reconsider? Eur. Heart J., January 2, 2002; 23(2): 95 - 97. [Full Text] [PDF]