Abstract 9685: Pharmacodynamic and Pharmacokinetic Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-Treatment: The SWAP-5 Study

Abstract

Introduction: The lack of drug-drug-interaction (DDI) with the use of ticagrelor in cangrelor-treated patients was demonstrated in studies in which ticagrelor was given at the time of initiation or during cangrelor infusion. However, many patients are pre-treated with ticagrelor and to date there is no data to rule out a DDI when ticagrelor is given prior to starting cangrelor. Methods: SWAP-5 is a randomized, double-blind, placebo-controlled, cross-over, pharmacokinetic (PK) and pharmacodynamic (PD) study conducted in 20 patients with coronary artery disease on aspirin (81mg/qd). Patients were pre-treated with a 180-mg ticagrelor loading dose (LD) and after 1 hour were randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1-4 weeks of washout. PK analysis included plasma levels of ticagrelor and its active metabolite, and PD assessments included VerifyNow P2Y 12 reaction units (PRU), light transmittance aggregometry (LTA) with 20 μM ADP as agonist, and vasodilator-stimulated phosphoprotein (VASP), at baseline and 6 time points after ticagrelor LD. Results: Compared to placebo, adding cangrelor to patients pre-treated with ticagrelor resulted in a significant reduction in PRU at 30 min and 1 hour after starting infusion ( Figure ). At 2 hours after stopping the infusion, PRU was low and similar in both groups (16.9 vs. 12.6; mean difference: 4.3; 95% CI: -28.6 to 37.3), meeting the non-inferiority primary endpoint (pre-defined non-inferiority margin 45 PRU). LTA and VASP showed consistent findings. PK tracked PD findings with no difference between groups in plasma levels of ticagrelor and its metabolite (data not shown). Conclusions: SWAP-5 is the first PK/PD study supporting the feasibility of adding cangrelor in patients pre-treated with ticagrelor. This approach resulted in lower levels of platelet reactivity during cangrelor infusion with similar PK/PD profiles after stopping the infusion and no evidence of DDI.