Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Subjects With Stable Coronary Artery Disease: Results of the SWAP-2 Study
What is the pharmacodynamic impact of switching from ticagrelor to prasugrel?
The authors measured platelet reactivity in 110 patients with stable coronary artery disease who were initially treated for 3- to 5-day run-in phase with ticagrelor 180 mg loading dose followed by ticagrelor 90 mg twice-daily in addition to aspirin, and were randomized to continue ticagrelor or switch to prasugrel 10 mg once-daily with or without a 60 mg loading dose. Pharmacodynamic assessments were defined by P2Y12 reaction unit (PRU; VerifyNow® P2Y12 assay) and platelet reactivity index (PRI; vasodilator-stimulated phosphoprotein phosphorylation assay) at baseline (before and after the run-in phase) and 2, 4, 24, and 48 hours and 7 days after randomization.
Platelet reactivity was significantly greater at 24 and 48 hours after switching to prasugrel versus continued therapy with ticagrelor. This difference was smaller in patients receiving a loading dose of prasugrel. Mean PRU remained significantly higher in the combined prasugrel group versus ticagrelor (least-squares mean difference: 46; 95% confidence interval [CI], 25-67) and did not meet the primary noninferiority endpoint (upper limit of the CI, ≤45). PRU in the prasugrel cohort was lower at 7 days than at 24 or 48 hours. Rates of high on-treatment platelet reactivity (HPR) were higher at 24 and 48 hours in patients randomized to prasugrel groups, although at 7 days, there was no difference in HPR frequency between the combined prasugrel and ticagrelor groups.
Among patients originally treated with ticagrelor, switching from ticagrelor to prasugrel therapy is associated with an increase in platelet reactivity that is partially mitigated by the administration of a loading dose.
Both ticagrelor and prasugrel are seeing increased use in contemporary practice (Karve, Circulation 2013;128:A15418). It is occasionally necessary to switch patients from one drug to the other (e.g., due to side effects, or to facilitate compliance with once a day dosing), and this study suggests that doing so may not result in similar platelet inhibition. Use of a loading dose of prasugrel appears to result in better platelet inhibition, albeit still not equivalent to that seen with continuing ticagrelor. The clinical significance of this remains unclear; however, should it be necessary to switch from ticagrelor to prasugrel, it appears prudent to initiate the switch with a loading dose of prasugrel.
Clinical Topics: Atherosclerotic Disease (CAD/PAD)
Keywords: Coronary Artery Disease, Platelet Aggregation Inhibitors, Blood Platelets, Purinergic P2Y Receptor Antagonists
< Back to Listings