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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J. L. Anderson, C. D. Adams, E. M. Antman, C. R. Bridges, R. M. Califf, D. E. Casey Jr, W. E. Chavey II, F. M. Fesmire, J. S. Hochman, T. N. Levin, et al. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine J. Am. Coll. Cardiol., August 14, 2007; 50(7): e1 - e157. [Full Text] [PDF]
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J. L. Anderson, C. D. Adams, E. M. Antman, C. R. Bridges, R. M. Califf, D. E. Casey Jr, W. E. Chavey II, F. M. Fesmire, J. S. Hochman, T. N. Levin, et al. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine J. Am. Coll. Cardiol., August 14, 2007; 50(7): 652 - 726. [Full Text] [PDF]
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N. von Beckerath, A. Kastrati, A. Wieczorek, G. Pogatsa-Murray, D. Sibbing, I. Graf, and A. Schomig A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days Eur. Heart J., August 1, 2007; 28(15): 1814 - 1819. [Abstract] [Full Text] [PDF]
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C. Bode and M. Zehender The use of antiplatelet agents following percutaneous coronary intervention: focus on late stent thrombosis Eur. Heart J. Suppl., August 1, 2007; 9(suppl_D): D10 - D19. [Abstract] [Full Text] [PDF]
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D. R. Holmes Jr, D. J. Kereiakes, W. K. Laskey, A. Colombo, S. G. Ellis, T. D. Henry, J. J. Popma, P. W.J.C. Serruys, T. Kimura, D. O. Williams, et al. Thrombosis and Drug-Eluting Stents: An Objective Appraisal J. Am. Coll. Cardiol., July 10, 2007; 50(2): 109 - 118. [Abstract] [Full Text] [PDF]
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Authors/Task Force Members, J.-P. Bassand, C. W. Hamm, D. Ardissino, E. Boersma, A. Budaj, F. Fernandez-Aviles, K. A.A. Fox, D. Hasdai, E. M. Ohman, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology Eur. Heart J., July 1, 2007; 28(13): 1598 - 1660. [Full Text] [PDF]
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D. J. Moliterno and C. L. Campbell Unraveling Questions Surrounding Clopidogrel Resistance and Stent Thrombosis: One Less Snag J. Am. Coll. Cardiol., June 19, 2007; 49(24): 2318 - 2319. [Full Text] [PDF]
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P. Buonamici, R. Marcucci, A. Migliorini, G. F. Gensini, A. Santini, R. Paniccia, G. Moschi, A. M. Gori, R. Abbate, and D. Antoniucci Impact of Platelet Reactivity After Clopidogrel Administration on Drug-Eluting Stent Thrombosis J. Am. Coll. Cardiol., June 19, 2007; 49(24): 2312 - 2317. [Abstract] [Full Text] [PDF]
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 T. A. Meadows and D. L. Bhatt Clinical Aspects of Platelet Inhibitors and Thrombus Formation Circ. Res., May 11, 2007; 100(9): 1261 - 1275. [Abstract] [Full Text] [PDF]
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A. O. Maree and D. J. Fitzgerald Variable Platelet Response to Aspirin and Clopidogrel in Atherothrombotic Disease Circulation, April 24, 2007; 115(16): 2196 - 2207. [Full Text] [PDF]
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