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Clopidogrel Resistance Associated with Increased Heart Attack Risk

Christopher P. Martin, Pharm.D.*
Edited by Henry I. Bussey, Pharm.D.
July, 2004

The clinical importance of clopidogrel is discussed in the June 29, 2004 issue of Circulation through an original research article 1 and an editorial 2.

The report by Maetetzky, et al links clopidogrel resistance to an increase in clinical events in 60 patients taking clopidogrel following stent placement for an acute myocardial infarction. Patients were grouped into quartiles based on in vitro platelet aggregometry testing. Among the 15 patients in the lowest quartile of responders to clopidogrel (i.e. those most resistant to clopidogrel) 6 (40%) experienced a recurrent event within six months. Only 1 of 15 patients in the second quartile (the next most clopidogrel resistant group) had a recurrent event while no recurrent events occurred in the other two quartile groups (i.e. those not resistance to clopidogrel). Of the 7 recurrent events, 5 were acute coronary events, 1 was peripheral arterial occlusion, and 1 was a fatal stroke. Although confirmation of the clinical importance of clopidogrel resistance in a larger study would be helpful, the present study suggests that clopidogrel resistance may be an important risk determinant of recurrent event risk in the post PCI period. At this time there are no data to guide us in how to manage the patients who are resistant to clopidogrel. Alternatives worth investigating include whether a larger dose of clopidogrel may over-come this resistance or whether newer antiplatelet agents may offer benefit.


1. Maetetzky S, Shenkman B, Guetta V, Shechter M, Bienart R, Goldenberg I, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004; 109:3171-3175.

2. Wiviott SD and Antman EM. Clopidogrel resistance, A new chapter in a fast-moving story. Circulation 2004; 109:3064-3067.

*Dr. Martin, who is a guest editor, is a Masters Candidate and Pharmacotherapy Resident in the College of Pharmacy at the University of Texas at Austin and the University of Texas Health Science Center at San Antonio.

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