This Article Full Text Full Text (PDF) All Versions of this Article: 108/18/2195    most recent 01.CIR.0000099507.32936.C0v1 Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Müller, I. Articles by Gawaz, M. Search for Related Content PubMed PubMed Citation Articles by Müller, I. Articles by Gawaz, M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Angina Blood Thinners Statins Related Collections Cardiovascular Pharmacology Secondary prevention Aggregation Platelet function inhibitors Catheter-based coronary interventions: stents Chronic ischemic heart disease Platelets

(Circulation. 2003;108:2195.)
© 2003 American Heart Association, Inc.

Brief Rapid Communications

Effects of Statins on Platelet Inhibition by a High Loading Dose of Clopidogrel

Iris Müller, MD; Felicitas Besta, PhD; Christian Schulz, MD; Zhongyan Li, MD; Steffen Massberg, MD; Meinrad Gawaz, MD

From Medizinische Klinik, Klinikum rechts der Isar und Deutsches Herzzentrum, Technische Universität München, Germany.

Correspondence to Meinrad Gawaz, MD, 1 Medizinische Klinik und Deutsches Herzzentrum, Technische Universität München, Klinikum rechts der Isar, Ismaninger Straße 22, 81675 München, Germany. E-mail meinrad.gawaz{at}med1.med.tu-muenchen.de

Received March 7, 2003; de novo received July 14, 2003; revision received September 16, 2003; accepted September 18, 2003.

Background— Recent studies suggested that some HMG-CoA reductase blockers might inhibit the antiplatelet activity of clopidogrel. Therefore, we analyzed how various statins together with a high loading dose of clopidogrel (600 mg) affect platelet aggregation.

Methods and Results— Seventy-seven patients with stable angina scheduled for elective coronary stenting were studied. Patients were randomized to receive atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin (each 20 mg), cerivastatin (0.3 mg), or placebo, plus a high loading dose of 600 mg of clopidogrel. ADP-induced platelet aggregation (5 and 20 µmol/L) was determined before and 2 and 4 hours after first clopidogrel administration. All patients were taking aspirin (100 mg/d) regularly. We found that none of the statins significantly influenced inhibition of platelet aggregation by clopidogrel.

Conclusions— Concomitant use of statins with clopidogrel does not significantly inhibit antiplatelet activity, at least when clopidogrel is administered at a high loading dose of 600 mg.

Key Words: platelets • stents • coronary disease • prevention

This article has been cited by other articles:

				C. Verstuyft, T. Simon, and R. B. Kim Personalized medicine and antiplatelet therapy: ready for prime time? Eur. Heart J., August 2, 2009; 30(16): 1943 - 1963. [Full Text] [PDF]

				C. Varenhorst, S. James, D. Erlinge, J. T. Brandt, O. O. Braun, M. Man, A. Siegbahn, J. Walker, L. Wallentin, K. J. Winters, et al. Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease Eur. Heart J., July 2, 2009; 30(14): 1744 - 1752. [Abstract] [Full Text] [PDF]

				R. Bhindi, O. Ormerod, J. Newton, A.P. Banning, and L. Testa Interaction between statins and clopidogrel: is there anything clinically relevant? QJM, December 1, 2008; 101(12): 915 - 925. [Abstract] [Full Text] [PDF]

				J. M. Siller-Matula, I. Lang, G. Christ, and B. Jilma Calcium-Channel Blockers Reduce the Antiplatelet Effect of Clopidogrel J. Am. Coll. Cardiol., November 4, 2008; 52(19): 1557 - 1563. [Abstract] [Full Text] [PDF]

				T. Geisler, C. Zurn, M. Paterok, K. Gohring-Frischholz, B. Bigalke, K. Stellos, P. Seizer, B. F. Kraemer, J. Dippon, A. E. May, et al. Statins do not adversely affect post-interventional residual platelet aggregation and outcomes in patients undergoing coronary stenting treated by dual antiplatelet therapy Eur. Heart J., July 1, 2008; 29(13): 1635 - 1643. [Abstract] [Full Text] [PDF]

				J. Saw, D. M. Brennan, S. R. Steinhubl, D. L. Bhatt, K.-H. Mak, K. Fox, E. J. Topol, and on behalf of the CHARISMA Investigators Lack of Evidence of a Clopidogrel Statin Interaction in the CHARISMA Trial J. Am. Coll. Cardiol., July 24, 2007; 50(4): 291 - 295. [Abstract] [Full Text] [PDF]

				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]

				M. Piorkowski, S. Fischer, C. Stellbaum, M. Jaster, P. Martus, A. J. Morguet, H.-P. Schultheiss, and U. Rauch Treatment With Ezetimibe Plus Low-Dose Atorvastatin Compared With Higher-Dose Atorvastatin Alone: Is Sufficient Cholesterol-Lowering Enough to Inhibit Platelets? J. Am. Coll. Cardiol., March 13, 2007; 49(10): 1035 - 1042. [Abstract] [Full Text] [PDF]

				J. Turgeon, C. Pharand, and V. Michaud Understanding clopidogrel efficacy in the presence of cytochrome P450 polymorphism Can. Med. Assoc. J., June 6, 2006; 174(12): 1729 - 1729. [Full Text] [PDF]

				K D Dawkins, T Gershlick, M de Belder, A Chauhan, G Venn, P Schofield, D Smith, J Watkins, H H Gray, and Joint Working Group on Percutaneous Coronary Inter Percutaneous coronary intervention: recommendations for good practice and training Heart, December 1, 2005; 91(suppl_6): vi1 - vi27. [Abstract] [Full Text] [PDF]

				E. R. Bates, W. C. Lau, and B. E. Bleske Loading, Pretreatment, and Interindividual Variability Issues With Clopidogrel Dosing Circulation, May 24, 2005; 111(20): 2557 - 2559. [Full Text] [PDF]

				W. Hochholzer, D. Trenk, D. Frundi, P. Blanke, B. Fischer, K. Andris, H.-P. Bestehorn, H. J. Buttner, and F.-J. Neumann Time Dependence of Platelet Inhibition After a 600-mg Loading Dose of Clopidogrel in a Large, Unselected Cohort of Candidates for Percutaneous Coronary Intervention Circulation, May 24, 2005; 111(20): 2560 - 2564. [Abstract] [Full Text] [PDF]

				E. R. Bates and W. C. Lau Controversies in Antiplatelet Therapy for Patients With Cardiovascular Disease Circulation, May 3, 2005; 111(17): e267 - e271. [Full Text] [PDF]

				T. A. Nguyen, J. G. Diodati, and C. Pharand Resistance to clopidogrel: A review of the evidence J. Am. Coll. Cardiol., April 19, 2005; 45(8): 1157 - 1164. [Abstract] [Full Text] [PDF]

				D Mukherjee, E Kline-Rogers, J Fang, K Munir, and K A Eagle Lack of clopidogrel-CYP3A4 statin interaction in patients with acute coronary syndrome Heart, January 1, 2005; 91(1): 23 - 26. [Abstract] [Full Text] [PDF]

				D. J. Angiolillo, A. Fernandez-Ortiz, E. Bernardo, C. Ramirez, M. Sabate, C. Banuelos, R. Hernandez-Antolin, J. Escaned, R. Moreno, F. Alfonso, et al. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability Eur. Heart J., November 1, 2004; 25(21): 1903 - 1910. [Abstract] [Full Text] [PDF]

				M. Cattaneo Aspirin and Clopidogrel: Efficacy, Safety, and the Issue of Drug Resistance Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 1980 - 1987. [Abstract] [Full Text] [PDF]

				S. P. Schulman Antiplatelet Therapy in Non-ST-Segment Elevation Acute Coronary Syndromes JAMA, October 20, 2004; 292(15): 1875 - 1882. [Abstract] [Full Text] [PDF]

				C. J. Vaughan and A. M. Gotto Jr Update on Statins: 2003 Circulation, August 17, 2004; 110(7): 886 - 892. [Full Text] [PDF]

				W. C. Lau, D. G.M. Carville, E. R. Bates, J. V. Mitsios, A. I. Papathanasiou, F. I. Rodis, M. Elisaf, J. A. Goudevenos, and A. D. Tselepis Clinical Significance of the Atorvastatin-Clopidogrel Drug-Drug Interaction * Response Circulation, August 10, 2004; 110(6): e66 - e67. [Full Text] [PDF]

				D. Williams, I. Ford, G. Hawksworth, J. V. Mitsios, A. I. Papathanasiou, F. I. Rodis, M. Elisaf, J. A. Goudevenos, and A. D. Tselepis Potential Statin-Clopidogrel Interaction Requires More Study * Response Circulation, August 10, 2004; 110(6): e68 - e68. [Full Text] [PDF]

				S. Bellosta, R. Paoletti, and A. Corsini Safety of Statins: Focus on Clinical Pharmacokinetics and Drug Interactions Circulation, June 15, 2004; 109(23_suppl_1): III-50 - III-57. [Abstract] [Full Text]

				J. V. Mitsios, A. I. Papathanasiou, F. I. Rodis, M. Elisaf, J. A. Goudevenos, and A. D. Tselepis Atorvastatin Does Not Affect the Antiplatelet Potency of Clopidogrel When It Is Administered Concomitantly for 5 Weeks in Patients With Acute Coronary Syndromes Circulation, March 23, 2004; 109(11): 1335 - 1338. [Abstract] [Full Text] [PDF]

				W. W. O'Neill and S. R. Dixon The year in interventional cardiology J. Am. Coll. Cardiol., March 3, 2004; 43(5): 875 - 890. [Full Text] [PDF]

				A. Lepantalo, K. S Virtanen, J. Heikkila, U. Wartiovaara, and R. Lassila Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions Eur. Heart J., March 2, 2004; 25(6): 476 - 483. [Abstract] [Full Text] [PDF]

				R. SoRelle Cardiovascular News Circulation, November 4, 2003; 108 (18): e9047 - e9048. [Full Text]