School of Pharmacology, University of South China, Hengyang, Hunan, People's Republic of China.
The Affiliated Nanhua Hospital, Department of Pharmacy, Hengyang Medical School University of South China, Hengyang, Hunan, People's Republic of China.
Drug Des Devel Ther. 2024 May 27;18:1811-1819. doi: 10.2147/DDDT.S458299. eCollection 2024.
Mechanistic studies showed that morphine may impair the antiplatelet effect of P2Y12 inhibitors. However, Several clinical studies with cardiovascular events as an outcome are contradictory, and the broader impact of this drug interaction on additional organ systems remains uncertain. With multisource data, this study sought to determine the effects of morphine interaction with P2Y12 inhibitors on major adverse outcomes comprehensively, and identify the warning indicators.
Interaction signals were sought in 187,919 safety reports from the FDA Adverse Event Reporting System (FAERS) database, utilizing reporting odds ratios (repOR). In a cohort of 5240 acute coronary syndrome patients, the analyses were validated, and the biological effects of warning indicators were further studied with Mendelian randomization and mediation analysis.
Potential risk of renal system adverse events in patients cotreated with morphine is significantly higher in FAERS (repOR 4.83, 95% CI 4.42-5.28, false discovery rate adjusted- =3.55*10). The analysis of in-house patient cohorts validated these results with an increased risk of acute kidney injury (adjusted OR: 1.65; 95% CI: 1.20 to 2.26), and we also found a risk of myocardial infarction in patients treated with morphine (adjusted OR: 1.55; 95% CI: 1.14 to 2.11). The Morphine group exhibited diminished Plateletcrit (PCT) levels post-surgery and lower PCT levels were associated with an increased risk of AKI.
The administration of morphine in patients treated with P2Y12 receptor inhibitors should be carefully evaluated. PCT may serve as a potential warning indicator for morphine-related renal injury.
机制研究表明，吗啡可能会削弱 P2Y12 抑制剂的抗血小板作用。然而，几项以心血管事件为结局的临床研究结果相互矛盾，这种药物相互作用对其他器官系统的广泛影响仍不确定。本研究利用多源数据，全面评估吗啡与 P2Y12 抑制剂相互作用对主要不良结局的影响，并确定预警指标。
在 FDA 不良事件报告系统（FAERS）数据库中，利用报告比值比（repOR）从 187919 份安全性报告中寻找相互作用信号。在 5240 例急性冠状动脉综合征患者的队列中进行分析验证，并通过孟德尔随机化和中介分析进一步研究预警指标的生物学效应。
在 FAERS 中，与吗啡联合治疗的患者发生肾脏系统不良事件的风险显著增加（repOR 4.83，95%CI 4.42-5.28，校正后的假发现率为 3.55*10）。内部患者队列的分析验证了这些结果，发现吗啡治疗的患者发生急性肾损伤的风险增加（校正后的 OR：1.65；95%CI：1.20 至 2.26），我们还发现吗啡治疗的患者发生心肌梗死的风险增加（校正后的 OR：1.55；95%CI：1.14 至 2.11）。吗啡组术后血小板压积（PCT）水平降低，且 PCT 水平较低与 AKI 风险增加相关。
在接受 P2Y12 受体抑制剂治疗的患者中，应谨慎使用吗啡。PCT 可能是吗啡相关肾损伤的潜在预警指标。
