Author + information
- Received February 19, 2016
- Revision received February 26, 2016
- Accepted February 26, 2016
- Published online June 13, 2016.
- Francesco Franchi, MD,
- Gabriel Todd Faz, MD,
- Fabiana Rollini, MD,
- Yongwhi Park, MD,
- Jung Rae Cho, MD,
- Estela Thano, MD,
- Jenny Hu, MD,
- Megha Kureti, MD,
- Niti Aggarwal, MD,
- Ashwin Durairaj, MD,
- Latonya Been, AAS,
- Martin M. Zenni, MD,
- Luis A. Guzman, MD,
- Siva Suryadevara, MD,
- Patrick Antoun, 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 This study sought to assess the pharmacodynamic (PD) effects of switching to ticagrelor patients who were treated with prasugrel after undergoing percutaneous coronary intervention in the setting of an acute coronary syndrome.
Background In clinical practice, there is a frequent need to switch between P2Y12 receptor inhibitors. However, concerns on drug interactions have emerged when switching therapies. To date, the PD effects of switching from prasugrel to ticagrelor have yet to be investigated.
Methods This was a prospective, randomized, open-label, 3-arm, parallel-design study conducted in patients (n = 82) on maintenance dual antiplatelet therapy with aspirin (81 mg QD) and prasugrel (10 mg QD). Patients were randomized to continue prasugrel 10 mg QD or switch to ticagrelor 90 mg bid, with or without a 180 mg loading dose (LD), for 1 week. PD assessments included P2Y12 reaction units (PRU) by VerifyNow, platelet reactivity index by vasodilator-stimulated phosphoprotein (VASP), and platelet aggregation by light transmittance aggregometry (LTA) at a total of 6 time points: baseline, 2 h, 4 h, 24 h, 48 h, and 1 week after randomization.
Results After switching to ticagrelor, PRU levels decreased as early as 2 h after drug administration. Mean PRU levels remained low during the study time course, without evidence of drug interactions. The primary endpoint of noninferiority of ticagrelor (2 arms combined) versus prasugrel measured by PRU at 1 week was met (least squares mean difference: –18; 95% confidence interval: –41 to 5). There was no increase in rates of high on-treatment platelet reactivity (PRU >208), which were overall very low throughout the study time course. Similar levels of platelet reactivity were observed irrespective of the use of a ticagrelor LD. Parallel findings were observed with VASP and LTA.
Conclusions Switching from prasugrel to ticagrelor leads to transiently higher levels of platelet inhibition, irrespective of the use of a LD, without evidence of drug interactions. (Pharmacodynamic Evaluation of Switching From Prasugrel to Ticagrelor [SWAP3]; NCT02016170)
The present study was funded by an investigator-initiated grant from AstraZeneca. AstraZeneca had no role in study design conception, conduct of the study, or decision to publish these results. Dr. Angiolillo has received payment or honorarium as an individual for serving as a consultant for Sanofi, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck, Abbott Vascular, and PLx Pharma as well as participation in review activities for CeloNova, Johnson & Johnson, and St. Jude Medical; and he has received institutional payments for grants from GlaxoSmithKline, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Janssen Pharmaceuticals, Inc., Osprey Medical, Inc., Novartis, CSL Behring, and Gilead. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Franchi and Faz contributed equally to this work.
- Received February 19, 2016.
- Revision received February 26, 2016.
- Accepted February 26, 2016.
- American College of Cardiology Foundation