Testing for the possibility of a drug-drug interaction (DDI) in patients undergoing percutaneous coronary intervention (PCI), investigators found that “concomitant administration of prasugrel with cangrelor leads to a marked increase in platelet reactivity after stopping cangrelor infusion.” The results support the presence of a DDI, the authors conclude.
In the SWAP-6 (Switching Antiplatelet-6) open-label pharmacokinetic (PK) and pharmacodynamic (PD) study, 77 patients were randomized to (1) prasugrel only at the start of PCI, (2) cangrelor plus prasugrel concomitantly at the start of PCI, or (3) cangrelor at the start of PCI plus prasugrel at the end of infusion. Based on a primary endpoint of noninferiority in VerifyNow (Werfen) P2Y12 reaction units measured at 4 hours after randomization between cangrelor plus prasugrel concomitantly administered vs prasugrel only, the authors found: “Compared with prasugrel, cangrelor further enhances P2Y12 inhibitory effects. At 4 hours postrandomization, P2Y12 reaction unit levels were significantly lower with prasugrel only compared to cangrelor and prasugrel concomitantly administered (least squares means difference = 130; 95% CI: 85-176), failing to meet the prespecified noninferiority margin. Findings were corroborated by multiple PD assays. The active metabolite of prasugrel levels were not affected by concomitant administration of cangrelor and were low at the end of cangrelor infusion.”