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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Bozzi, LM; Mitchell, BD; Lewis, JP; Ryan, KA; Herzog, WR; O'Connell, JR; Horenstein, RB; Shuldiner, AR; Yerges-Armstrong, LM

Published Date

  • 2016

Published In

Volume / Issue

  • 14 / 1

Start / End Page

  • 116 - 124

PubMed ID

  • 26374108

Pubmed Central ID

  • 26374108

Electronic International Standard Serial Number (EISSN)

  • 1875-6212

Language

  • eng

Conference Location

  • United Arab Emirates