NEW YORK (Reuters Health) – Whether clopidogrel is abruptly stopped or slowly tapered, there is no evidence of a rebound in platelet activity, German researchers report.

They point out that observations of clustered thrombotic events in patients who’ve stopped taking clopidogrel had been blamed on a platelet rebound phenomenon — but the existence of such a phenomenon had never been proven.

Also, speculation about a rebound effect had led to a theory that tapering clopidogrel, rather than abruptly stopping it, might avoid the problem.

In the Journal of the American College of Cardiology for February 9, lead author Dr. Dirk Sibbing, from Deutsches Herzzentrum Munchen, and his colleagues report on their investigations of both of these questions – does a rebound effect exist, and if so, would tapering prevent it?

Their study involved 69 patients who were receiving clopidogrel 75 mg after drug-eluting stent placement and were planning to stop the drug. They were randomized either to taper the drug dose over 4 weeks and then stop, or to continue the drug at the same dose for 4 weeks and then abruptly stop.

Platelet aggregation, induced by adenosine diphosphate (ADP), was measured with light transmission aggregometry and multiple electrode aggregometry at baseline and at weeks 2 to 8 after randomization.

First, the changes in platelet aggregation values after clopidogrel discontinuation did not indicate the presence of a rebound phenomenon.

Second, tapering clopidogrel did not result in significantly lower values compared to abrupt discontinuation.

Still, the authors believe that tapering clopidogrel could, in theory, offer advantages over stopping abruptly. While tapering did not lead to lower absolute platelet aggregation values, it did result in a more gradual rise in values, and this gradual increase might reduce the risk of thrombotic events, they suggest.

The clinical benefits of tapered versus abrupt clopidogrel cessation will be examined in the ISAR-CAUTION trial, the researchers note.

Reference:

J Am Coll Cardiol 2010;55:558-565.