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The "Plavix Rebound" Phenomenon


Updated June 04, 2014

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  • An article in today's (February 6) Journal of the American Medical Association suggests that, in patients who have been treated with either stents or medical therapy for acute coronary artery syndromes (ACS, that is, either heart attack or unstable angina), suddenly stopping Plavix (clopidogrel) may be associated with a "rebound" effect. This rebound effect is manifested by the sudden occlusion of the coronary artery, leading to heart attack or death.

    Plavix reduces the function of blood platelets, and thus reduces the chance that a blood clot will form in the diseased coronary artery after treatment. Therapy with Plavix is currently recommended for one year after treatment for ACS, and is often continued for longer than one year if a drug-eluting stent has been used as part of that treatment.

    In monitoring 3137 patients who received Plavix after being treated for ACS, the authors of this new study say that the patients' chance of having a heart attack or dying was nearly twice as high during the 90 days after Plavix was stopped, than it was after this 90-day interval. They speculate that perhaps tapering Plavix instead of stopping it abruptly, or perhaps increasing the dose of aspirin during the first 90 days after stopping Plavix, may help to reduce this rebound effect - but of course, more studies will need to be done to see whether either of these strategies are effective.

    DrRich Comments:

    This study is the first to document an apparent increase in risk immediately after Plavix therapy is stopped. However, any regular visitor to our forum will be familiar with the phenomenon, since we've heard plenty of stories there that fit with the notion of a "Plavix rebound." Also, one suspects that many (if not most) cardiologists have their own experiences in this regard, considering their otherwise inexplicable vehemence in refusing to allow their patients to stop Plavix long enough to have needed surgical procedures.

    So, we owe thanks to the authors of this new article for bringing this problem, at last, out into the light of day.

    Patients with ACS need aggressive therapy in any case, in order to optimize their odds of long-term survival. And with any aggressive therapy there will be inherent risks. It is therefore useful to have those risks fully defined. The only good way to get around the risks of treatment, unfortunately, is to do everything possible to avoid needing treatment in the first place, by aggressively managing cardiac risk factors.

    Where this new information really ought to make a difference is in patients whose doctors are recommending stent placement (as opposed to medical therapy) for stable coronary artery disease. Doctors are obligated to fully inform those patients of the risks of stent placement, and now, for the first time, one of the risks that they're obligated to describe is the possibility of a Plavix rebound.


    Ho PM, Peterson ED, Wang L, et al. Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome. JAMA 2008; 299:532-539.

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