Abstract 14004: Pharmacodynamic Profiles of Ticagrelor in Patients With ST-Elevation Myocardial Infarction: A Prospective Randomized Comparison of Escalating Loading Dose Regimens
Background: Pharmacodynamic (PD) studies have shown that in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI), ticagrelor is associated with suboptimal platelet inhibition and elevated rates of high on-treatment platelet reactivity (HPR) in the early hours after loading dose (LD) administration. Impaired absorption affecting drug pharmacokinetics (PK) has been hypothesized as a contributing factor suggesting increasing LD regimens to improve PK/PD profiles. To date there are no randomized studies which have investigated the PK/PD effects of escalating ticagrelor LD regimens in patients undergoing PPCI.
Methods: In this prospective, randomized study, STEMI patients undergoing PPCI (n=52) were randomized 1:1:1 to receive 180mg, 270mg or 360mg LD of ticagrelor. PK and PD analysis were performed before and at 6 time points after LD. PD assessments included P2Y12 reaction units (PRU) measured by VerifyNow P2Y12 and platelet reactivity index (PRI) measured by VASP. PK assessments included plasma concentrations of ticagrelor and its metabolite AR-C124910XX.
Results: At baseline there were no differences in platelet reactivity between groups. At 2 hrs (primary endpoint), there were no differences in PRU between groups (p=0.54). There were no differences in PRU between groups during the overall study time course (p=0.17; Figure). Accordingly, HPR (PRU>208) at 2 hrs was observed in 30% of patients and was not reduced by escalating ticagrelor LD regimens. Consistent PD findings were observed with VASP-PRI. PK data tracked PD results, with a non-dose related delay in peak plasma concentrations of both ticagrelor and AR-C124910XX, particularly in HPR patients.
Conclusions: In STEMI patients undergoing PPCI, increasing the LD regimen of ticagrelor did not translate into more prompt or potent P2Y12 inhibition, which is attributed to impaired absorption in the early hours after drug administration.
Author Disclosures: F. Franchi: None. F. Rollini: None. J. Cho: None. M. Bhatti: None. C. DeGroat: None. E. Ferrante: None. E.C. Dunn: None. A. Nanavati: None. E. Carraway: None. S. Suryadevara: None. M.M. Zenni: None. L.A. Guzman: None. T.A. Bass: None. D.J. Angiolillo: Research Grant; Significant; Bristol Myers Squibb, Sanofi-Aventis, Glaxo Smith Kline, Otsuka, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Evolva, and Gilead.. Honoraria; Significant; Bristol Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck, Evolva, Abbott Vascular, Bayer, and PLx Pharma. Consultant/Advisory Board; Significant; Johnson & Johnson, St. Jude, Sunovion, and CeloNova.
- © 2014 by American Heart Association, Inc.