Abstract 12493: Impact of Ticagrelor Re-Load on Pharmacodynamic Profiles in Patients on Maintenance Ticagrelor Therapy
Background: Although ticagrelor is associated with superior clinical efficacy than clopidogrel, ticagrelor-treated patients may still require subsequent revascularization procedures, either due to acute or chronic progression of atherosclerotic disease. However, the optimal dosing regimen of ticagrelor to be administered among patients already on maintenance therapy has been questioned.
Methods: This was a prospective, randomized, double-blind study assessing the pharmacodynamic (PD) effects of two dosing regimens of ticagrelor among patients already on standard aspirin (81 mg/qd) and ticagrelor (90 mg bid) maintenance therapy for at least 14 days. Patients were randomized to either 90 mg (MD group; one 90 mg tablet and one matching placebo) or 180 mg (LD group; two 90 mg tablets). Study treatment was administered 12 hours after the last maintenance dose (timing of trough PD level). PD assessments were conducted at 3 time-points (baseline, 1 hour and 4 hours after administration of randomized treatment) using multiple assays, including vasodilator-stimulated phosphoprotein (VASP), VerifyNow P2Y12, and light transmittance aggregometry (LTA). The platelet reactivity index (PRI) as assessed by VASP was the PD assay considered for the primary endpoint measure.
Results: There were no differences in baseline levels of platelet reactivity with all assays. VASP-PRI was reduced after ticagrelor administration at 1 and 4 hours, with a greater magnitude of effects observed in the LD compared with the MD group (Figure). Significant differences between groups over time were confirmed in an adjusted ANCOVA analysis (p=0.031). Consistent findings were found in P2Y12 reaction units (PRU) as assessed by VerifyNow (p=0.026) and ADP (20μM)-induced platelet aggregation by LTA (p=0.004).
Conclusions: In patients on maintenance ticagrelor therapy, a 180 mg re-loading dose of ticagrelor is associated with more potent PD effects compared with a maintenance dose regimen.
Author Disclosures: J. Cho: None. F. Rollini: None. F. Franchi: None. A. Muniz-Lozano: None. C. DeGroat: None. M. Bhatti: None. E. Ferrante: None. M. Taha: None. E.C. Dunn: 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.