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Clopidogrel Rebound?

An observational study reveals high adverse event rates within 90 days of discontinuation of clopidogrel after ACS.

Clopidogrel reduces the risk for cardiovascular events after acute coronary syndromes, but it is unknown whether clopidogrel cessation might provoke a "rebound" phenomenon (a clustered increase in events) similar to that observed upon discontinuation of aspirin or heparin. To explore this possibility, investigators retrospectively assessed the rates of adverse events in U.S. veterans who had been discharged from 127 Veterans Affairs hospitals after ACS and who received postdischarge treatment with clopidogrel.

Of 1568 patients who had received only medical treatment for ACS, subsequent death or acute MI occurred in 17.1%, and the preponderance of events (60.8%) occurred in the first 90 days after stopping clopidogrel therapy. Of 1569 patients who had undergone percutaneous coronary intervention, subsequent death or acute MI occurred in 7.9%; again, the majority of events (58.9%) occurred in the first 90 days after clopidogrel discontinuation. Multivariable analysis showed a nearly twofold increase in risk for adverse events during the first 90 days after clopidogrel cessation in both the medically treated and the PCI-treated patients (incident rate ratios, 1.98 and 1.82, respectively).

Comment: In this nationwide retrospective study of veterans, a substantial clustering of adverse events was observed in the 90 days immediately following clopidogrel cessation after acute coronary syndromes, both in patients treated medically and in those treated with percutaneous coronary intervention. Further studies are needed to confirm these findings and to explore whether their magnitude, which seems to exceed what one would expect simply from loss of the benefit conferred by clopidogrel, is a true rebound effect. In the meantime, clinicians should do their best to ensure that patients take their prescribed clopidogrel. In addition, extending the duration of clopidogrel therapy may improve clinical outcomes in patients at high risk for thrombosis and low risk for bleeding.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology February 5, 2008

Citation(s):

Ho PM et al. Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome. JAMA 2008 Feb 6; 299:532.

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