The pharmacogenomics of anti-platelet intervention (PAPI) study: Variation in platelet response to clopidogrel and aspirin

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, Laura M. Yerges-Armstrong

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)116-124
Number of pages9
JournalCurrent Vascular Pharmacology
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Anti-platelet therapies
  • Aspirin
  • Clopidogrel
  • Pharmacogenomics
  • Platelet aggregation
  • Short-term intervention

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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