Variability in platelet responsiveness to clopidogrel among 544 individuals
| Autor: | Steven R. Steinhubl, Eric J. Topol, Alex I. Malinin, Peter B. Berger, Deepak L. Bhatt, Victor L. Serebruany |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Ticlopidine Time Factors Platelet Aggregation Drug Resistance Platelet Membrane Glycoproteins Antigens CD Risk Factors Internal medicine medicine Distribution (pharmacology) Humans Platelet cardiovascular diseases Platelet activation Dosing Stroke Aged Retrospective Studies business.industry Middle Aged Clopidogrel medicine.disease Surgery Clinical trial Cardiovascular Diseases Heart failure Cardiology Female Cardiology and Cardiovascular Medicine business Platelet Aggregation Inhibitors circulatory and respiratory physiology medicine.drug |
| Zdroj: | Journal of the American College of Cardiology. 45(2) |
| ISSN: | 0735-1097 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|