Department of Cardiology, Geneva University Hospitals, Geneva, Switzerland.
Department of Cardiology, Cardiocentro Ticino, Lugano, Switzerland, Switzerland.
Cardiol J. 2022;29(4):591-600. doi: 10.5603/CJ.a2022.0049. Epub 2022 Jun 28.
Morphine reduces absorption and delays action onset of potent oral P2Y₁₂ receptor inhibitors in patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the differential effects of fentanyl compared to morphine on the pharmacodynamics and pharmacokinetics of ticagrelor in STEMI patients undergoing primary percutaneous coronary intervention (PCI).
PERSEUS (NCT02531165) was a prospective, single-center, open-label, randomized controlled study. Patients with STEMI who required analgesia were randomly assigned in a 1:1 ratio to treatment with intravenous fentanyl or morphine after ticagrelor loading dose (LD) administration. The primary endpoint was platelet reactivity at 2 hours after ticagrelor LD assessed by P2Y₁₂ reaction units (PRU).
The study was prematurely stopped in June 2017 after enrolment of 38 out of 56 planned patients. PRU at 2 hours following ticagrelor LD was 173.3 ± 89.7 in the fentanyl group and 210.3 ± 76.4 in the morphine group (p = 0.179). At 4 hours, PRU was significantly lower among patients treated with fentanyl as compared to those treated with morphine (90.1 ± 97.4 vs. 168.0 ± 72.2; p = 0.011). Maximal plasma concentrations of ticagrelor and its active metabolite AR-C124910XX tended to be delayed and numerically lower among patients treated with morphine compared to fentanyl. Total exposures to ticagrelor and AR-C124910XX within 6 hours after ticagrelor LD were numerically greater among patients treated with fentanyl compared to those treated with morphine.
In patients with STEMI undergoing primary PCI, fentanyl did not improve platelet inhibition at 2 hours after ticagrelor pre-treatment compared with morphine. Fentanyl may, however, accelerate ticagrelor absorption and increase platelet inhibition at 4 hours compared to morphine.
吗啡会降低 ST 段抬高型心肌梗死（STEMI）患者对强效口服 P2Y₁₂ 受体抑制剂的吸收，并延迟其起效时间。我们旨在确定与吗啡相比，芬太尼对行经皮冠状动脉介入治疗（PCI）的 STEMI 患者使用替格瑞洛的药效学和药代动力学的影响。
PERSEUS（NCT02531165）是一项前瞻性、单中心、开放标签、随机对照研究。需要镇痛的 STEMI 患者在替格瑞洛负荷剂量（LD）给药后，按 1:1 的比例随机分配至静脉注射芬太尼或吗啡治疗组。主要终点是通过 P2Y₁₂ 反应单位（PRU）评估替格瑞洛 LD 后 2 小时的血小板反应性。
在计划入组的 56 例患者中，入组 38 例后，该研究于 2017 年 6 月提前终止。替格瑞洛 LD 后 2 小时时，芬太尼组的 PRU 为 173.3±89.7，吗啡组为 210.3±76.4（p=0.179）。4 小时时，与吗啡组相比，芬太尼组的 PRU 显著降低（90.1±97.4 vs. 168.0±72.2；p=0.011）。与芬太尼组相比，吗啡组替格瑞洛及其活性代谢物 AR-C124910XX 的最大血浆浓度趋于延迟且数值较低。与吗啡组相比，替格瑞洛 LD 后 6 小时内替格瑞洛和 AR-C124910XX 的总暴露量在芬太尼组中数值更大。
在接受经皮冠状动脉介入治疗的 STEMI 患者中，与吗啡相比，芬太尼并未改善替格瑞洛预处理后 2 小时的血小板抑制作用。然而，与吗啡相比，芬太尼可能会加速替格瑞洛的吸收，并在 4 小时时增加血小板抑制作用。
