title: Inhibition of platelet aggregation with prasugrel and clopidogrel: an integrated analysis in 846 subjects.
abstract: This integrated analysis compared speed of onset, level of platelet inhibition, and response variability to prasugrel and clopidogrel in healthy subjects and in patients with stable coronary artery disease with data pooled from 24 clinical pharmacology studies. Data from subjects (N = 846) were categorized into the following treatment groups: prasugrel 60 mg loading dose (LD)/10 mg maintenance dose (MD), clopidogrel 300 mg LD/75 mg MD, or clopidogrel 600 mg LD/75 mg MDs. Maximum platelet aggregation (MPA) and inhibition of platelet aggregation (IPA) to 5 and 20 muM ADP were assessed by turbidimetric aggregometry. A linear mixed-effect model compared the MPA and IPA between treatments over time points evaluated in the integrated database, and covariates affecting platelet inhibition were identified. Prasugrel 60 mg LD resulted in faster onset, greater magnitude, and more consistent levels of inhibition of platelet function compared to either clopidogrel 300 mg or 600 mg LDs. Greater and more consistent levels of platelet inhibition were observed with the prasugrel 10 mg MD compared to the clopidogrel 75 mg MD. This integrated analysis confirms the findings of earlier individual studies, that prasugrel achieves faster onset of greater extent and more consistent platelet inhibition compared to the approved and higher loading doses of clopidogrel. Gender, race, body weight, and age were identified as statistically significant covariates impacting platelet inhibition.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. li_ying_grace@lilly.com
authors.forename: Ying G
authors.initials: YG
authors.lastname: Li
authors.forename: Lan
authors.initials: L
authors.lastname: Ni
authors.forename: John T
authors.initials: JT
authors.lastname: Brandt
authors.forename: David S
authors.initials: DS
authors.lastname: Small
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Payne
authors.forename: C Steven
authors.initials: CS
authors.lastname: Ernest
authors.forename: Shashank
authors.initials: S
authors.lastname: Rohatagi
authors.forename: Nagy A
authors.initials: NA
authors.lastname: Farid
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jakubowski
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Winters
mesh_terms: D000328:Adult; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy; D003625:Data Collection; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D000068799:Prasugrel Hydrochloride; D013876:Thiophenes / Q000493:pharmacokinetics / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D055815:Young Adult
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine