Abstract
Objective: Clopidogrel discontinuation is associated with increased incidence of ischemic events, which may signal a pharmacological rebound. We evaluated the impact of clopidogrel discontinuation on platelet function in CAD patients. Methods: Platelet aggregation was measured by VerifyNow ® P2Y 12 and by light transmission aggregometry (LTA) in response to ADP 1, 2, 3, 5, 10, and 20 μ M, in 37 CAD patients scheduled to discontinue clopidogrel treatment (aspirin treated patients clinically stable 1 year after clopidogrel initiation), and 37 CAD patients not taking clopidogrel. Platelet function was assessed the day before clopidogrel cessation and 1, 3, 7, 14, 21, 28 days after. Results: Subjects were on average 65±10 years old, and presented classic CAD risk factors similarly treated between groups. Subjects discontinuing clopidogrel were more likely to have undergone stenting. VerifyNow ® P2Y 12 did not detect any rebound platelet activity, but ADP-induced LTA showed significant increase in platelet aggregation, particularly at low ADP levels, suggestive of platelet hypersensitivity (Fig ). Rebound platelet activity was detectable at 7 days after clopidogrel cessation, and remained higher than in controls 28 days of discontinuation. No clinical events were seen at 28 days in either group. Conclusion: Platelet sensitization to ADP as a consequence of chronic clopidogrel administration may partially explain the recrudescence of ischemic events following clopidogrel discontinuation in otherwise stable CAD patients. Further research into the pathophysiological processes of platelet function recovery is required. Figure: Platelet aggregation as a function of time
Published Version
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