Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA.
Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA; Maria Cecilia Hospital, Gruppo Villa Maria Care and Research, Cotignola, Italy.
JACC Cardiovasc Interv. 2023 Oct 23;16(20):2528-2539. doi: 10.1016/j.jcin.2023.08.009. Epub 2023 Aug 21.
A drug-drug interaction (DDI) may occur when transitioning from intravenous P2Y inhibition with cangrelor to oral P2Y inhibition with prasugrel. However, this has never been tested in patients undergoing percutaneous coronary intervention (PCI).
This study sought to rule out a DDI when cangrelor and prasugrel are concomitantly administered in PCI patients.
SWAP-6 (Switching Antiplatelet-6) was a prospective, randomized, 3-arm, open-label pharmacokinetic (PK) and pharmacodynamic (PD) study. Patients (N = 77) 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. Cangrelor infusion was maintained for 2 hours. PK/PD assessments were performed at baseline and 6 time points postrandomization. The primary endpoint was noninferiority in VerifyNow (Werfen) P2Y reaction units measured at 4 hours after randomization between cangrelor plus prasugrel concomitantly administered vs prasugrel only. PK assessments included plasma levels of the active metabolite of prasugrel.
Compared with prasugrel, cangrelor further enhances P2Y inhibitory effects. At 4 hours postrandomization, P2Y 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.
In patients undergoing PCI, concomitant administration of prasugrel with cangrelor leads to a marked increase in platelet reactivity after stopping cangrelor infusion, supporting the presence of a DDI. (Switching Antiplatelet Therapy-6 [SWAP-6]; NCT04668144).
当从静脉注射的 P2Y 抑制药物坎格瑞洛转换为口服 P2Y 抑制药物普拉格雷时，可能会发生药物-药物相互作用（DDI）。然而，这在接受经皮冠状动脉介入治疗（PCI）的患者中从未得到过验证。
本研究旨在排除 PCI 患者同时使用坎格瑞洛和普拉格雷时发生 DDI 的可能性。
SWAP-6（Switching Antiplatelet-6）是一项前瞻性、随机、三臂、开放性药代动力学（PK）和药效学（PD）研究。患者（N=77）被随机分为 1）仅在 PCI 开始时使用普拉格雷，2）在 PCI 开始时同时使用坎格瑞洛和普拉格雷，或 3）在 PCI 开始时使用坎格瑞洛，在输注结束时使用普拉格雷。坎格瑞洛输注持续 2 小时。在随机分组后 6 个时间点进行 PK/PD 评估。主要终点是在随机分组后 4 小时，与单独使用普拉格雷相比，同时使用坎格瑞洛和普拉格雷的 VerifyNow（Werfen）P2Y 反应单位的非劣效性。PK 评估包括普拉格雷活性代谢物的血浆水平。
与普拉格雷相比，坎格瑞洛进一步增强了 P2Y 抑制作用。与单独使用普拉格雷相比，在随机分组后 4 小时，同时使用坎格瑞洛和普拉格雷的 P2Y 反应单位水平显著降低（最小二乘均数差值=130；95%CI：85-176），未能达到预设的非劣效性边界。这一发现得到了多种 PD 检测的证实。同时使用坎格瑞洛并不影响普拉格雷的活性代谢物水平，且在坎格瑞洛输注结束时，其水平较低。
在接受 PCI 的患者中，同时使用坎格瑞洛和普拉格雷会导致停止坎格瑞洛输注后血小板反应性显著增加，支持存在 DDI。（Switching Antiplatelet Therapy-6 [SWAP-6]；NCT04668144）。
