TY - JOUR
T1 - Pharmacodynamic evaluation of switching from ticagrelor to prasugrel in patients with stable coronary artery disease
T2 - Results of the swap-2 study (switching anti platelet-2)
AU - Angiolillo, Dominick J.
AU - Curzen, Nicholas
AU - Gurbel, Paul
AU - Vaitkus, Paul
AU - Lipkin, Fred
AU - Li, Wei
AU - Jakubowski, Joseph A.
AU - Zettler, Marjorie
AU - Effron, Mark B.
AU - Trenk, Dietmar
N1 - Funding Information:
The authors thank Kathy Stoakes, RN, BSN, Clinical Study Leader, for ensuring data integrity through oversight and management of the study. Bret Fulton, RPh, and Maria McGill, RPh, CMPP, of inScience Communications, Springer Healthcare, provided medical writing support funded by Daiichi Sankyo, Inc .
PY - 2014/4/22
Y1 - 2014/4/22
N2 - 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.
AB - 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.
KW - drug interaction
KW - pharmacodynamics
KW - platelet function
KW - prasugrel
KW - ticagrelor
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UR - http://www.scopus.com/inward/citedby.url?scp=84902089776&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2013.11.032
DO - 10.1016/j.jacc.2013.11.032
M3 - Article
C2 - 24333493
AN - SCOPUS:84902089776
SN - 0735-1097
VL - 63
SP - 1500
EP - 1509
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 15
ER -