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The Platelet Activity After Clopidogrel Termination (PACT) study.
MedLine Citation:
PMID:  20736449     Owner:  NLM     Status:  In-Process    
BACKGROUND: "Rebound" platelet hyperreactivity after 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. We therefore performed a randomized, double-blind, placebo-controlled, crossover study: the Platelet Activity after Clopidogrel Termination (PACT) study.
METHODS AND RESULTS: Platelet reactivity in 15 healthy subjects was measured at baseline, 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. Platelet reactivity was assessed by (1) platelet surface activated GPIIb-IIIa and surface P-selectin (by whole blood flow cytometry) in response to ADP 0.5, 1, and 20 μmol/L; thrombin receptor activating peptide (TRAP) 1 and 20 μmol/L; and collagen/epinephrine 5 μg/mL/5 μmol/L, (2) light transmission aggregation with ADP 2.5, 5, and 20 μmol/L; TRAP 2 and 20 μmol/L; and collagen 6 μg/mL, (3) whole blood impedance aggregation with ADP 1.6 and 6.5 μmol/L; TRAP 4 and 32 μmol/L; and collagen 3.2 μg/mL, and (4) plasma soluble CD40 ligand (by ELISA). Immature platelet fraction was measured in the Sysmex XE-2100. At no time point after discontinuation of clopidogrel was platelet reactivity, as determined by any assay end point, or the immature platelet fraction significantly greater than after discontinuation of placebo.
CONCLUSIONS: This randomized, 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.
CLINICAL TRIAL REGISTRATION: URL: Unique identifier: NCT00619073.
Andrew L Frelinger; Marc R Barnard; Marsha L Fox; Alan D Michelson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-24
Journal Detail:
Title:  Circulation. Cardiovascular interventions     Volume:  3     ISSN:  1941-7632     ISO Abbreviation:  Circ Cardiovasc Interv     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101499602     Medline TA:  Circ Cardiovasc Interv     Country:  United States    
Other Details:
Languages:  eng     Pagination:  442-9     Citation Subset:  IM    
Center for Platelet Research Studies, Division of Hematology/Oncology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115-5737, USA.
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