Abstract 15908: A Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Patients With Stable Coronary Artery Disease: Results of the SWAP-2 Study
Background: The availability of several oral antiplatelet agents has raised the need to define how to optimally switch among therapies. Pharmacodynamic ( PD) data are lacking on the effect of switching from ticagrelor (T) to prasugrel (P). SWAP-2 was a randomized, multicenter, parallel-design study to determine the PD effects of switching from T to P.
Methods: After 3-5 days (d) run-in with T 180 mg loading dose (LD)/90 mg bid maintenance dose (MD), 98 subjects with stable CAD on aspirin therapy (75-150 mg), 18-75 years, were randomized (1:1:1) to receive P 60 mg LD/10 mg qd MD (Arm A), P 10 mg qd MD (Arm B), or T 90 mg bid MD (Arm C) for 7 d. Platelet reactivity using VerifyNow® P2Y12 (VN) and VASP assays were assessed at baseline (pre-randomization), 2, 4, 24, 48 hrs, and 7 d after randomization. The primary hypothesis was that after 7 d of randomized treatment, P2Y12 Reaction Units (PRU) by VN would be non-inferior in subjects switched from T to P compared with subjects remaining on T ([Arms A + B] vs. Arm C) using 45 PRU as the non-inferiority (NI) margin for the upper CI limit of the difference.
Results: At 7 d, the PRU was 96±54 vs. 48±48 in the P vs. T arms, respectively (Figure), leading to a least square mean difference of 46 PRU (95% CI 25, 67), thus not meeting the NI primary objective. However, rates of high on-treatment platelet reactivity (HPR) with P compared with T using PRU cut points of ≥208 or ≥230 were similar at 7 d. At 24 and 48 hrs, PRU increased in Arms A and B compared to pre-randomization values, with a greater increase in Arm B than Arm A. Similarly, rates of HPR were higher in Arm A and Arm B compared to Arm C at 24 and 48 hrs, and were greater in Arm B than Arm A at both time points.
Conclusion: SWAP-2 did not meet its primary objective of demonstrating NI of P vs. T after switching. These data suggest a potential PD interaction between T and P which appears to be mitigated with administration of a LD of P. The optimal timing between the discontinuation of T and administration of a LD of P remains to be determined.
- © 2013 by American Heart Association, Inc.