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The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin

[ Vol. 14 , Issue. 1 ]

Author(s):

Laura M. Bozzi, Braxton D. Mitchell, Joshua P. Lewis, Kathy A. Ryan, William R. Herzog, Jeffrey R. O’Connell, Richard B. Horenstein, Alan R. Shuldiner and Laura M. Yerges-Armstrong   Pages 116 - 124 ( 9 )

Abstract:


Clopidogrel and aspirin are commonly prescribed anti-platelet medications indicated for patients who have experienced, or are at risk for, ischemic cardiovascular events. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study was designed to characterize determinants of clopidogrel and dual anti-platelet therapy (DAPT) response in a healthy cohort of Old Order Amish from Lancaster, PA. Following a loading dose, clopidogrel was taken once a day for 7 days. One hour after the last dose of clopidogrel, 325 mg of aspirin was given. Ex vivo platelet aggregometry was performed at baseline, post-clopidogrel, and post-DAPT. Platelet aggregation measurements were significantly lower after both interventions for all agonists tested (p <0.05), although there was large inter-individual variation in the magnitude of anti-platelet response. Female sex and older age were associated with higher platelet aggregation at all three time-points. Change in aggregation was correlated among the various agonists at each time point. Heritability (h2) of change in platelet aggregation was significant for most traits at all time-points (range h2=0.14-0.57). Utilization of a standardized, short-term intervention provided a powerful approach to investigate sources of variation in platelet aggregation response due to drug therapy. Further, this short-term intervention approach may provide a useful paradigm for pharmacogenomics studies.

Keywords:

Anti-platelet therapies, aspirin, clopidogrel, pharmacogenomics, platelet aggregation, short-term intervention.

Affiliation:

University of Maryland Baltimore, 685 W. Baltimore St., MSTF 357, Baltimore, MD 21201, USA.

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