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Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Subjects With Stable Coronary Artery Disease: Results of the SWAP-2 Study
Study Questions:
What is the pharmacodynamic impact of switching from ticagrelor to prasugrel?
Methods:
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.
Results:
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.
Conclusions:
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.
Perspective:
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.
Keywords: Coronary Artery Disease, Platelet Aggregation Inhibitors, Blood Platelets, Purinergic P2Y Receptor Antagonists
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