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

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. (J Am Coll Cardiol 2010; 55: 558-65) (c) 2010 by the American College of Cardiology Foundation