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.