title: The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin.
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.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Bozzi
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Lewis
authors.forename: Kathy A
authors.initials: KA
authors.lastname: Ryan
authors.forename: William R
authors.initials: WR
authors.lastname: Herzog
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: O'Connell
authors.forename: Richard B
authors.initials: RB
authors.lastname: Horenstein
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.affiliation: University of Maryland Baltimore, 685 W. Baltimore St., MSTF 357, Baltimore, MD 21201, USA. lyerges@medicine.umaryland.edu.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Yerges-Armstrong
mesh_terms: D000328:Adult; D000367:Age Factors; D061365:Amish / Q000235:genetics; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012737:Sex Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin