Circulation. 2004;109:3171-3175
Published online before print June 7, 2004, doi: 10.1161/01.CIR.0000130846.46168.03
Published online before print June 7, 2004, doi: 10.1161/01.CIR.0000130846.46168.03
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(Circulation. 2004;109:3171-3175.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Clopidogrel Resistance Is Associated With Increased Risk of Recurrent Atherothrombotic Events in Patients With Acute Myocardial Infarction
From the Heart Institute (S.M., V.G., M.S., R.B., I.G., I.N., H.P., H.H.), Institute of Thrombosis and Hemostasis (B.S., D.V.), and Goldschleger Eye Research Institute (N.S.), Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Correspondence to Hanoch Hod, MD, Director, ICCU, Heart Institute, Sheba Medical Center, Tel Hashomer 52621, Israel. E-mail hod{at}netvision.net.il
Received October 20, 2003; de novo received December 14, 2003; revision received February 24, 2004; accepted March 16, 2004.
Background— Although clopidogrel reduces the risk of cardiovascular episodes after coronary events and stenting, a substantial number of incidents continue to occur.
Methods and Results— The antiplatelet effect of clopidogrel was studied prospectively in 60 consecutive patients who underwent primary angioplasty (percutaneous coronary intervention [PCI]) with stenting for acute ST-segment–elevation myocardial infarction (STEMI) to determine whether variability in response to clopidogrel affects clinical outcomes. Patients were stratified into 4 quartiles according to the percentage reduction of ADP-induced platelet aggregation. Although patients in the first quartile were resistant to the effects of clopidogrel (ADP-induced platelet aggregation at day 6, 103±8% of baseline), ADP-induced aggregation was reduced to 69±3%, 58±7%, and 33±12% of baseline, respectively, in patients in quartiles 2 through 4 (P<0.01 for all). In addition, epinephrine-induced platelet aggregation and platelet aggregation under flow conditions, assessed by the cone-and-plate(let) analyzer method, were reduced significantly less in the first quartile than in quartiles 2 through 4. Whereas 40% of patients in the first quartile sustained a recurrent cardiovascular event during a 6-month follow-up, only 1 patient (6.7%) in the second quartile and none in the third and fourth quartiles suffered a cardiovascular event (P=0.007).
Conclusions— Up to 25% of STEMI patients undergoing primary PCI with stenting are resistant to clopidogrel and therefore may be at increased risk for recurrent cardiovascular events.
Key Words: platelets • myocardial infarction • clopidogrel
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T. Cuisset, C. Frere, J. Quilici, P.-E. Morange, L. Nait-Saidi, J. Carvajal, A. Lehmann, M. Lambert, J.-L. Bonnet, and M.-C. Alessi 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 J. Am. Coll. Cardiol., October 3, 2006; 48(7): 1339 - 1345. [Abstract] [Full Text] [PDF]
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T. Geisler, H. Langer, M. Wydymus, K. Gohring, C. Zurn, B. Bigalke, K. Stellos, A. E. May, and M. Gawaz Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation Eur. Heart J., October 2, 2006; 27(20): 2420 - 2425. [Abstract] [Full Text] [PDF]
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A. D. Michelson, A. L. Frelinger, and M. I. Furman Resistance to antiplatelet drugs Eur. Heart J. Suppl., October 1, 2006; 8(suppl_G): G53 - G58. [Abstract] [Full Text] [PDF]
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D. J. Kereiakes and E. M. Antman Clinical Guidelines and Practice: In Search of the Truth J. Am. Coll. Cardiol., September 19, 2006; 48(6): 1129 - 1135. [Abstract] [Full Text] [PDF]
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A. L. Beitelshees and H. L. McLeod Clopidogrel pharmacogenetics: promising steps towards patient care? Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1681 - 1683. [Full Text] [PDF]
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D. J. Angiolillo, A. Fernandez-Ortiz, E. Bernardo, C. Ramirez, U. Cavallari, E. Trabetti, M. Sabate, R. Hernandez, R. Moreno, J. Escaned, et al. Contribution of Gene Sequence Variations of the Hepatic Cytochrome P450 3A4 Enzyme to Variability in Individual Responsiveness to Clopidogrel Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1895 - 1900. [Abstract] [Full Text] [PDF]
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D. J. Angiolillo, E. Bernardo, C. Ramirez, M. A. Costa, M. Sabate, P. Jimenez-Quevedo, R. Hernandez, R. Moreno, J. Escaned, F. Alfonso, et al. Insulin Therapy Is Associated With Platelet Dysfunction in Patients With Type 2 Diabetes Mellitus on Dual Oral Antiplatelet Treatment J. Am. Coll. Cardiol., July 18, 2006; 48(2): 298 - 304. [Abstract] [Full Text] [PDF]
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V L Serebruany, M G Midei, H Meilman, A I Malinin, and D R Lowry Platelet inhibition with prasugrel (CS-747) compared with clopidogrel in patients undergoing coronary stenting: the subset from the JUMBO study. Postgrad. Med. J., June 1, 2006; 82(968): 404 - 410. [Abstract] [Full Text] [PDF]
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T. Jernberg, C. D. Payne, K. J. Winters, C. Darstein, J. T. Brandt, J. A. Jakubowski, H. Naganuma, A. Siegbahn, and L. Wallentin Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease Eur. Heart J., May 2, 2006; 27(10): 1166 - 1173. [Abstract] [Full Text] [PDF]
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S. Husted, H. Emanuelsson, S. Heptinstall, P. M. Sandset, M. Wickens, and G. Peters Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin Eur. Heart J., May 1, 2006; 27(9): 1038 - 1047. [Abstract] [Full Text] [PDF]
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