Author + information
- Received December 9, 2014
- Revision received February 16, 2015
- Accepted February 18, 2015
- Published online July 1, 2015.
- Jung Rae Cho, MD,
- Fabiana Rollini, MD,
- Francesco Franchi, MD,
- Christopher DeGroat, MD,
- Mona Bhatti, MD,
- Elizabeth C. Dunn, RN,
- Elisabetta Ferrante, PhD,
- Ana Muniz-Lozano, MD,
- Siva Suryadevara, MD,
- Martin M. Zenni, MD,
- Luis A. Guzman, MD,
- Theodore A. Bass, MD and
- Dominick J. Angiolillo, MD, PhD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Dominick J. Angiolillo, University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, Florida 32209.
Objectives The aim of this study was to assess the impact of ticagrelor dosing regimens on pharmacodynamic (PD) profiles in patients on maintenance ticagrelor therapy.
Background Many patients on maintenance P2Y12-inhibiting therapies may require coronary revascularization procedures, raising a common clinical question with regard to the dosing regimen of the P2Y12-inhibiting agent to be used. To date, investigations assessing dosing regimens of P2Y12 receptor inhibitors in patients on maintenance therapy have been only assessed with thienopyridines, but not with ticagrelor.
Methods This was a prospective, randomized, double-blind, placebo-controlled study assessing the PD effects of 2 dosing regimens of ticagrelor in patients on standard aspirin and ticagrelor maintenance therapy. A total of 60 patients were randomized to either 90 mg (maintenance dose [MD] group) or 180 mg (loading dose [LD] group) dose of ticagrelor. PD assessments were conducted at 3 time points (baseline, 1 h and 4 h). PD assessments were defined according to the platelet reactivity index (PRI) (vasodilator-stimulated phosphoprotein phosphorylation assay), P2Y12 reaction unit (VerifyNow P2Y12 assay) and adenosine diphosphate–induced platelet aggregation by light transmittance aggregometry.
Results There were no differences in baseline levels of platelet reactivity with all assays. Intergroup comparisons by means of repeated-measures analysis adjusted for baseline PRI values showed that the LD group had significantly lower PRI levels compared with the MD group during the overall study time course (p = 0.031). Consistent findings were found for P2Y12 reaction unit (p = 0.026) and light transmittance aggregometry (p = 0.004). Intragroup comparisons showed that a more prompt and sustained platelet inhibitory effect was achieved more consistently with an LD regimen compared with a MD regimen.
Conclusions In patients on maintenance ticagrelor therapy, a 180-mg LD regimen of ticagrelor is associated with more potent and prompt platelet inhibition compared with a 90-mg MD. (Impact of Ticagrelor Re-Load Pharmacodynamic Profiles; NCT01731041).
The present study was funded by an investigator-initiated grant from AstraZeneca. AstraZeneca had no role in the analysis, study design, or decision to publish these results. Dr. Angiolillo has received consulting fees or honoraria from Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck, Abbott Vascular, Sanofi, Bayer and PLx Pharma; has participated in review activities for CeloNova, Johnson & Johnson, and St. Jude Medical; and has received institutional payments for grants from Gilead, GlaxoSmithKline, Eli Lilly, Daiichi Sankyo, The Medicines Company, Osprey Medical, Inc, Janssen Pharmaceuticals, Inc, Novartis, CSL Behring, and AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received December 9, 2014.
- Revision received February 16, 2015.
- Accepted February 18, 2015.
- 2015 American College of Cardiology Foundation