Circulation. 2003;107:2908-2913
Published online before print June 9, 2003, doi: 10.1161/01.CIR.0000072771.11429.83
Published online before print June 9, 2003, doi: 10.1161/01.CIR.0000072771.11429.83
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(Circulation. 2003;107:2908.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Clopidogrel for Coronary Stenting
Response Variability, Drug Resistance, and the Effect of Pretreatment Platelet Reactivity
From the Sinai Center for Thrombosis Research (P.A.G., K.P.B., B.L.H.), Baltimore, Md, and Duke Clinical Research Institute (C.M.O.), Durham, NC.
Correspondence to Paul A. Gurbel, MD, Sinai Center for Thrombosis Research, Hoffberger Bldg, Suite 56, 2401 W Belvedere Ave, Baltimore, MD 21215. E-mail pgurbel{at}lifebridgehealth.org
Background— Clopidogrel is administered to prevent stent thrombosis; however, the uniformity of platelet inhibition after treatment and the influence of pretreatment reactivity on drug response have not been described.
Methods and Results— Platelet aggregation (5 and 20 µmol/L ADP), the activation of glycoprotein IIb/IIIa (PAC-1 antibody), and the expression of P-selectin were measured in patients undergoing elective coronary stenting (n=96) at baseline and at 2 hours, 24 hours, 5 days, and 30 days after stenting. All patients received aspirin (325 mg). Clopidogrel (300 mg) was administered in the catheterization laboratory and followed by 75 mg daily. There was marked interindividual variability in drug response as measured by all markers that showed a normal distribution. Resistance, defined as baseline aggregation (%) minus posttreatment aggregation (%) ≤10% by 5 µmol/L ADP, was present in 31% and 15% of patients at 5 and 30 days, respectively. Patients with the highest pretreatment platelet reactivity remained the most reactive at 24 hours after treatment (P<0.0001).
Conclusions— Interindividual variability in the platelet inhibitory response from clopidogrel occurs in patients undergoing elective coronary stenting. Patients with high pretreatment reactivity are least protected. Alternative pharmacological strategies and the association of adverse ischemic events should be investigated in these patients.
Key Words: drugs • platelets • stents
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D. J. Angiolillo, E. Bernardo, M. Sabate, P. Jimenez-Quevedo, M. A. Costa, J. Palazuelos, R. Hernandez-Antolin, R. Moreno, J. Escaned, F. Alfonso, et al. Impact of Platelet Reactivity on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease J. Am. Coll. Cardiol., October 16, 2007; 50(16): 1541 - 1547. [Abstract] [Full Text] [PDF]
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G. Campo, M. Valgimigli, D. Gemmati, G. Percoco, L. Catozzi, A. Frangione, F. Federici, F. Ferrari, M. Tebaldi, S. Luccarelli, et al. Poor Responsiveness to Clopidogrel: Drug-Specific or Class-Effect Mechanism?: Evidence From a Clopidogrel-to-Ticlopidine Crossover Study J. Am. Coll. Cardiol., September 18, 2007; 50(12): 1132 - 1137. [Abstract] [Full Text] [PDF]
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 G. J. Weerakkody, J. A. Jakubowski, J. T. Brandt, C. D. Payne, H. Naganuma, and K. J. Winters Greater Inhibition of Platelet Aggregation and Reduced Response Variability With Prasugrel Versus Clopidogrel: An Integrated Analysis Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2007; 12(3): 205 - 212. [Abstract] [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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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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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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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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K. P. Bliden, J. DiChiara, U. S. Tantry, A. K. Bassi, S. K. Chaganti, and P. A. Gurbel Increased Risk in Patients With High Platelet Aggregation Receiving Chronic Clopidogrel Therapy Undergoing Percutaneous Coronary Intervention: Is the Current Antiplatelet Therapy Adequate? J. Am. Coll. Cardiol., February 13, 2007; 49(6): 657 - 666. [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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 G Kocabay, I Okcular, V Akkaya, and K. Guler Suicide attempt with clopidogrel Human and Experimental Toxicology, December 1, 2006; 25(12): 731 - 734. [Abstract] [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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G. Campo, M. Valgimigli, D. Gemmati, G. Percoco, S. Tognazzo, G. Cicchitelli, L. Catozzi, P. Malagutti, M. Anselmi, C. Vassanelli, et al. Value of Platelet Reactivity in Predicting Response to Treatment and Clinical Outcome in Patients Undergoing Primary Coronary Intervention: Insights Into the STRATEGY Study J. Am. Coll. Cardiol., November 9, 2006; (2006) j.jacc.2005.12.085v1. [Abstract] [Full Text] [PDF]
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W. Hochholzer, D. Trenk, H.-P. Bestehorn, B. Fischer, C. M. Valina, M. Ferenc, M. Gick, A. Caputo, H. J. Buttner, and F.-J. Neumann Impact of the Degree of Peri-Interventional Platelet Inhibition After Loading With Clopidogrel on Early Clinical Outcome of Elective Coronary Stent Placement J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1742 - 1750. [Abstract] [Full Text] [PDF]
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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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