1 Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden.
2 Perioperative Medicine and Intensive Care, B31 Karolinska University Hospital Huddinge, Stockholm Sweden.
J Am Heart Assoc. 2019 Jan 22;8(2):e010152. doi: 10.1161/JAHA.118.010152.
Background Morphine administration is a strong predictor of delayed onset of action of orally administered ticagrelor in patients with ST-segment-elevation myocardial infarction, likely because of impaired gastrointestinal motility. The aim of this study was to evaluate whether the peripheral opioid antagonist methylnaltrexone could improve pharmacodynamics and pharmacokinetics of orally administered ticagrelor in patients with ST-segment-elevation myocardial infarction receiving morphine. Methods and Results The MOVEMENT (Methylnaltrexone to Improve Platelet Inhibition of Ticagrelor in Morphine-Treated Patients With ST-Segment Elevation Myocardial Infarction) trial was a multicenter, prospective, randomized, controlled trial in patients with ST-segment-elevation myocardial infarction treated with morphine and ticagrelor. Upon arrival to the catheterization laboratory, patients were randomized to a blinded intravenous injection of either methylnaltrexone (8 or 12 mg according to weight) or 0.9% sodium chloride. The proportion of patients with high on-treatment platelet reactivity and plasma concentrations of ticagrelor and AR -C124910XX were assessed at baseline (arrival in the catheterization laboratory) and 1 and 2 hours later. A total of 82 patients received either methylnaltrexone (n=43) or placebo (n=39). Median (interquartile range) time from ticagrelor administration to randomization was 41 (31-50) versus 45.5 (37-60) minutes ( P=0.16). Intravenous methylnaltrexone administration did not significantly affect prevalence of high on-treatment platelet reactivity at 2 hours after inclusion, the primary end point, when compared with placebo (54% versus 51%, P=0.84). Plasma concentrations of ticagrelor and its active metabolite, the prespecified secondary end points, did not differ significantly between the groups over time. There was no significant difference in patient self-estimated pain between the groups. Conclusions Methylnaltrexone did not significantly improve platelet reactivity or plasma concentrations of orally administered ticagrelor in patients with ST-segment-elevation myocardial infarction receiving morphine. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02942550.
背景 吗啡给药是 ST 段抬高型心肌梗死患者口服替格瑞洛起效延迟的强预测因子，可能是由于胃肠道蠕动受损所致。本研究旨在评估外周阿片受体拮抗剂甲基纳曲酮是否可以改善接受吗啡治疗的 ST 段抬高型心肌梗死患者口服替格瑞洛的药效学和药代动力学。
方法和结果 MOVEMENT（甲基纳曲酮改善吗啡治疗的 ST 段抬高型心肌梗死患者的替格瑞洛血小板抑制作用）试验是一项多中心、前瞻性、随机、对照研究，纳入接受吗啡和替格瑞洛治疗的 ST 段抬高型心肌梗死患者。患者到达导管室后，按体重随机接受静脉注射甲基纳曲酮（8 或 12mg）或 0.9%氯化钠。在基线（到达导管室）以及 1 和 2 小时后评估高替格瑞洛治疗血小板反应性和替格瑞洛及 AR-C124910XX 血浆浓度的患者比例。共 82 例患者接受了甲基纳曲酮（n=43）或安慰剂（n=39）治疗。替格瑞洛给药至随机分组的中位（四分位距）时间为 41（31-50）与 45.5（37-60）分钟（P=0.16）。与安慰剂相比，静脉注射甲基纳曲酮给药在纳入后 2 小时（主要终点）时并未显著影响高替格瑞洛治疗血小板反应性的发生率，即 54%与 51%（P=0.84）。替格瑞洛及其活性代谢物的血浆浓度（预设次要终点）在两组之间随时间无显著差异。两组间患者自我评估的疼痛无显著差异。
结论 吗啡治疗的 ST 段抬高型心肌梗死患者中，甲基纳曲酮并未显著改善口服替格瑞洛的血小板反应性或血浆浓度。
http://www.clinicaltrials.gov。唯一标识符：NCT 02942550。
