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 Sibbing, D. Articles by Schömig, A. Search for Related Content PubMed PubMed Citation Articles by Sibbing, D. Articles by Schömig, A. Related Collections Related Article

CLINICAL RESEARCH: ANTIPLATELET THERAPY

A Double-Blind, Randomized Study on Prevention and Existence of a Rebound Phenomenon of Platelets After Cessation of Clopidogrel Treatment

Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

Manuscript received July 4, 2009; revised manuscript received September 4, 2009, accepted September 14, 2009.

^_* Reprint requests and correspondence: Dr. Dirk Sibbing, Deutsches Herzzentrum München, Lazarettstrasse 36, 80636 München, Germany (Email: dirk{at}sibbing.net).

Objectives: The goal of this study was to assess whether a platelet rebound exists and whether it can be attenuated by clopidogrel tapering.

Background: Clinical studies have reported a clustering of thrombotic events after stopping clopidogrel treatment. The hypothesis of a rebound phenomenon of platelets has been declared causative, but its existence has never been confirmed. Tapering of clopidogrel over a certain period of time before stopping the drug completely might provide a way to attenuate this supposed phenomenon.

Methods: Patients (n = 69) receiving clopidogrel treatment due to prior drug-eluting stent placement and planning to stop clopidogrel were recruited in a double-blind, randomized trial. Patients were randomized to either receive a pre-specified tapering regimen (tapering group; n = 35) for 4 weeks with complete discontinuation of clopidogrel thereafter or continue a daily clopidogrel intake for 4 more weeks with abrupt discontinuation afterwards (off group; n = 34). Platelet aggregation (PA) was assessed with light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) simultaneously at study inclusion and at weeks 2 to 8 after randomization. The primary end point was the highest value of adenosine diphosphate–induced PA measured with LTA in the weeks after complete cessation of clopidogrel in both groups.

Results: The highest values of adenosine diphosphate–induced PA after complete cessation of clopidogrel were similar between both groups (p = 0.21 with LTA, and p = 0.55 with MEA).

Conclusions: Tapering of clopidogrel does not result in lower PA values after clopidogrel withdrawal. The course of PA values after clopidogrel cessation provides no evidence for the existence of a rebound phenomenon of platelets.

Key Words: clopidogrel • platelet aggregation • platelet rebound

Abbreviations and Acronyms   ADP = adenosine diphosphate   AU = aggregation units   CAD = coronary artery disease   DES = drug-eluting stent(s)   LTA = light transmission aggregometry   MEA = multiple electrode platelet aggregometry   PCI = percutaneous coronary intervention   PPP = platelet-poor plasma   PRP = platelet-rich plasma   ST = stent thrombosis   TRAP = thrombin-receptor activating peptide

Related Article

Inside This Issue
J. Am. Coll. Cardiol. 2010 55: A32. [Full Text] [PDF]

This article has been cited by other articles:

				N. Sambu, H. Dent, N. Englyst, T. D. Warner, P. Leadbeater, P. Roderick, H. Gray, I. Simpson, S. Corbett, A. Calver, et al. Effect of clopidogrel withdrawal on platelet reactivity and vascular inflammatory biomarkers 1 year after drug-eluting stent implantation: results of the prospective, single-centre CESSATION study Heart, October 15, 2011; 97(20): 1661 - 1667. [Abstract] [Full Text] [PDF]

				S. R. Dixon and C. L. Grines The Year in Interventional Cardiology J. Am. Coll. Cardiol., May 31, 2011; 57(22): 2207 - 2220. [Full Text] [PDF]

				D. J. Angiolillo, J. J. Badimon, J. F. Saucedo, A. L. Frelinger, A. D. Michelson, J. A. Jakubowski, B. Zhu, C. K. Ojeh, B. A. Baker, and M. B. Effron A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial Eur. Heart J., April 1, 2011; 32(7): 838 - 846. [Abstract] [Full Text] [PDF]

				K. G. Aragam and D. L. Bhatt Review: Antiplatelet Therapy in Acute Coronary Syndromes Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2011; 16(1): 24 - 42. [Abstract] [PDF]

				R. Hall and C. D. Mazer Review Article: Antiplatelet Drugs: A Review of Their Pharmacology and Management in the Perioperative Period Anesth. Analg., February 1, 2011; 112(2): 292 - 318. [Abstract] [Full Text] [PDF]

				A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, G. K. Feld, B. H. Greenberg, J. Hall, M. Hlatky, W. Y. W. Lew, J. A. C. Lima, A. S. Maisel, et al. Highlights of the Year in JACC 2010 J. Am. Coll. Cardiol., January 25, 2011; 57(4): 480 - 514. [Full Text] [PDF]

				A. L. Frelinger III, M. R. Barnard, M. L. Fox, and A. D. Michelson The Platelet Activity After Clopidogrel Termination (PACT) Study Circ Cardiovasc Interv, October 1, 2010; 3(5): 442 - 449. [Abstract] [Full Text] [PDF]