Clinical research
Antiplatelet therapy
Variability in platelet responsiveness to clopidogrel among 544 individuals

https://doi.org/10.1016/j.jacc.2004.09.067Get rights and content
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Objectives

We sought to describe the responses of patients to clopidogrel using ex vivo measures of platelet aggregation and activation in a large, heterogeneous population.

Background

Recently, a number of reports, using various definitions, have dichotomized patients who are treated with clopidogrel into a minority of “non-responders” and a majority of “responders.” Such classifications imply that treatment leads to an all-or-none response, with potentially important clinical implications.

Methods

We conducted secondary post-hoc analyses of a dataset consisting of volunteers (n = 94) and patients after coronary stenting (n = 405), with heart failure (n = 25), and after stroke (n = 20).

Results

The response of subjects to clopidogrel followed a normal, bell-shaped distribution, with a mean and standard deviation of 41.9 ± 20.8% when aggregation was induced by 5 μmol/l of adenosine diphosphate. When hyporesponsiveness and hyper-responsiveness to clopidogrel were considered to be two standard deviations less than and greater than the mean, respectively, the prevalence of hyporesponsiveness and hyper-responsiveness in these patients was 4.2% and 4.8%, respectively. Pretreatment platelet activity and clinical characteristics were not associated with responsiveness to clopidogrel.

Conclusions

Individuals receiving clopidogrel exhibit a wide variability in response that follows a normal distribution. The clinical implications of this variability are unknown but potentially are important. Clinical trials are needed to define whether hyporesponders to clopidogrel are at increased risk for thrombotic events and whether hyper-responders are at increased risk for bleeding. If so, the individualization of antiplatelet therapy, including clopidogrel dosing, may be possible in the future but will require the ability to easily and reproducibly measure responsiveness by a method that has been proven to be predictive of clinical events.

Abbreviations and acronyms

ADP
adenosine diphosphate
PRP
platelet-rich plasma

Cited by (0)

Drs. Serebruany, Steinhubl, Berger, and Topol have received research support from the Sanofi-BMS Partnership. Drs. Serebruany, Steinhubl, and Topol are consultants for Sanofi-BMS Partnership. Drs. Serebruany, Steinhubl, Berger, and Bhatt received honoraria for educational presentations for Sanofi-Synthelabo/Bristol-Myers Squibb Partnership. Dr. Serebruany is an owner of HeartDrugResearch LLC. The sponsors had no role in study design, data collection, data analyses, interpretation of results, or manuscript writing. The first two authors contributed equally to this study.