Title
Projected inhibition of platelet aggregation with ticagrelor twice daily vs. clopidogrel once daily based on patient adherence data ( the TWICE project) Projected inhibition of platelet aggregation with ticagrelor twice daily vs. clopidogrel once daily based on patient adherence data ( the TWICE project)
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
London ,
Subject
Pharmacology. Therapy
Source (journal)
British journal of clinical pharmacology. - London
Volume/pages
77(2014) :5 , p. 746-755
ISSN
0306-5251
ISI
000334782800003
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
AimTwice daily dosing is often perceived as inferior to once daily dosing due to a higher likelihood of missing a dose. However, more important is the extent to which drug action is maintained when doses are delayed or missed. We compared the estimated inhibition of platelet aggregation (eIPA) for ticagrelor twice daily and clopidogrel once daily, based on their pharmacokinetic/pharmacodynamic relationships and patient dosing history data. MethodsDrug dosing histories of 5014 patients prescribed cardiovascular medications (primarily antihypertensive medicines) were extracted from an electronically compiled dosing history database. eIPA levels were simulated for 677 twice daily and 677 once daily dosing histories over a 30day period, based on published onset/offset models for ticagrelor and clopidogrel IPA characteristics. ResultsWhile many patients treated twice daily missed at least one dose in 30days, only 25.7% missed two consecutive doses. By comparison, 46.8% of patients treated once daily missed at least one dose. Simulations based on patient adherence over time showed that the average mean eIPA for ticagrelor twice daily remained significantly higher than for clopidogrel once daily (81.1% vs. 55.0%, P < 0.001). Ticagrelor twice daily patients had an eIPA below 10% for 0.20% of the 30day period compared with 2.05% for clopidogrel once daily (P = 0.0001). ConclusionsThe projected level of platelet inhibition remained higher for ticagrelor twice daily than clopidogrel once daily, mainly due to the higher eIPA level achieved with ticagrelor and the relatively low likelihood of missing two consecutive twice daily doses. This modelling and simulation study suggests a therapeutic benefit of ticagrelor over clopidogrel when taking into account the most common dosing omissions.
E-info
https://repository.uantwerpen.be/docman/iruaauth/9d1311/ccc7668.pdf
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000334782800003&DestLinkType=RelatedRecords&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000334782800003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000334782800003&DestLinkType=CitingArticles&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
Handle