Abstract 5770: The Platelet Activity After Clopidogrel Termination (PACT) Study

Abstract

“Rebound” platelet hyperreactivity upon discontinuation of clopidogrel has been proposed to lead to increased thrombotic risk including late stent thrombosis. However the hypothesis that discontinuation of clopidogrel results in platelet hyperreactivity has never been rigorously tested. To test this, we performed a prospective, randomized, double-blind, placebo-controlled, crossover study: the Platelet Activity after Clopidogrel Termination (PACT) study. Platelet reactivity was measured before, during clopidogrel 75 mg or placebo daily for 14 days, and on days 1, 4, 8, 11, 15 and 45 after discontinuation of clopidogrel or placebo in 15 healthy subjects. All subjects received aspirin 81 mg daily. Platelet reactivity was assessed by platelet surface activated GPIIb-IIIa and surface P-selectin, measured by whole blood flow cytometry, in response to ADP 0.5, 1, and 20 μ M, thrombin receptor activating peptide (TRAP) 1 and 20 μ M, and both collagen 5 μ g/mL and epinephrine 5 μ M, and by light transmission platelet aggregation with ADP 2.5, 5, and 20 μ M, TRAP 2 and 20 μ M, and collagen 6 μ g/mL. Immature platelet fraction (IPF) was measured in the Sysmex XE-2100. At no time point after discontinuation of clopidogrel was platelet reactivity, as determined by all assay end points, or the IPF significantly greater than after discontinuation of placebo. The figure shows representative results. In conclusion, this double-blind, placebo-controlled, crossover study demonstrates that discontinuation of clopidogrel does not result in “rebound” platelet hyperreactivity -as determined by multiple time points, assays, agonists, and agonist concentrations. Fig. ADP 1 μM-stimulated platelet surface activated GPIIb-IIIa before, during, and after treatment with placebo or clopidogrel .