Cangrelor in Patients with Coronary Artery Disease Pre-treated with Ticagrelor: The Switching Antiplatelet (SWAP)-5 Study

To rule out a drug-drug interaction (DDI) among cangrelor-treated patients who have been pre-treated with ticagrelor.There are no studies specifically designed to rule out a DDI when cangrelor is used among patients who have been pre-treated with ticagrelor.In this prospective, randomized, double-blind, placebo-controlled, cross-over, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (n=20) were pre-treated with a 180-mg ticagrelor loading dose (LD) and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1-4 weeks of washout. PK analysis included ticagrelor plasma levels and its active metabolite. PD assessments included: VerifyNow P2YCompared 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. At 2 hours after stopping cangrelor/placebo infusion, PRU was low and similar in both groups (16.9 vs. 12.6; mean difference: 4.3; 95%CI: -28.6; 37.3), meeting the non-inferiority primary endpoint (pre-defined non-inferiority margin 45 PRU). Consistent findings were shown with all PD assays. PK tracked PD findings with no differences between groups in plasma levels of ticagrelor and its metabolite.Compared with placebo, the use of cangrelor in patients pre-treated with ticagrelor results in enhanced platelet inhibition with no differences in PK/PD profiles after discontinuation of drug infusion indicating the absence of a DDI.