Objectives: The goal of this study was to evaluate the pharmacodynamic effects of switching patients from ticagrelor to prasugrel.
Background: Clinicians may need to switch between more potent P2Y12 inhibitors because of adverse effects or switch to the use of a once-daily dosing regimen due to compliance issues.
Methods: After a 3- to 5-day run-in phase with a ticagrelor 180-mg loading dose (LD) followed by a ticagrelor 90-mg twice-daily maintenance dose (MD), aspirin-treated patients (N = 110) with stable coronary artery disease were randomized to continue ticagrelor or switch to prasugrel 10-mg once-daily MD, with or without a 60-mg LD. Pharmacodynamic assessments were defined according to P2Y12 reaction unit (PRU) (P2Y12 assay) and platelet reactivity index (vasodilator-stimulated phosphoprotein phosphorylation assay) at baseline (before and after the run-in phase) and 2, 4, 24, and 48 h and 7 days after randomization.
Results: Platelet reactivity was significantly greater at 24 and 48 h after switching to prasugrel versus continued therapy with ticagrelor, although to a lesser extent in those receiving an LD. Mean PRU remained significantly higher in the combined prasugrel groups versus the ticagrelor group (least-squares mean difference: 46 [95% confidence interval 25 to 67]) and did not meet the primary noninferiority endpoint (upper limit of the confidence interval ≤45), although PRU in the prasugrel cohort was lower at 7 days than at 24 or 48 h. Accordingly, rates of high on-treatment platelet reactivity were higher at 24 and 48 h in both prasugrel groups. At 7 days, there was no difference in high on-treatment platelet reactivity rate between the combined prasugrel and ticagrelor groups.
Conclusions: Compared with continued ticagrelor therapy, switching from ticagrelor to prasugrel therapy was associated with an increase in platelet reactivity that was partially mitigated by the administration of an LD.
Keywords: drug interaction; pharmacodynamics; platelet function; prasugrel; ticagrelor.
Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.