The Pharmaceutical Journal
Vol 280 No 7489 p171
16 February 2008

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Clopidogrel rebound reported

Evidence to support a rebound effect following withdrawal of clopidogrel treatment in patients with acute coronary syndrome (ACS) was reported last week in JAMA (2008;299:532). However, the researchers say that the findings do not necessarily offset the benefits of clopidogrel, rather that further research is needed to confirm the results and to better understand the pathophysiology of the phenomenon.

Rates of all-cause mortality and acute myocardial infarction were determined in a retrospective cohort study (sponsored by the US Department of Veterans Affairs) of 3,137 patients with ACS who were treated either medically or with percutaneous coronary intervention and subsequently prescribed clopidogrel for up to one year.

The researchers observed a clustering of events in the first 90 days after stopping clopidogrel among both medically treated and PCI-treated patients, although the number of events was low.
Among medically treated patients the mean duration of clopidogrel treatment was 302 days and for PCI-treated patients it was 203 days. Medically treated patients were almost twice as likely to die or have a myocardial infarction in the first 90 days after stopping clopidogrel than in the subsequent 90 days (incidence rate ratio 1.98, 95 per cent confidence interval 1.46–2.69). Similarly, PCI-treated patients had an 82 per cent increased risk of death or myocardial infarction in the first 90 days (1.82, 1.17–2.83).

“These findings support the hypothesis of a rebound hyperthrombotic period after stopping treatment with clopidogrel and highlight the need for additional studies to confirm these findings, to better understand the pathophysiology of this phenomenon and to identify strategies to attenuate this effect,” the researchers conclude.