| アブストラクト | PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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-P =3.55*10(-209)). 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. CONCLUSION: 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. |
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| ジャーナル名 | Drug design, development and therapy |
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| 投稿日 | 2024/6/3 |
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| 投稿者 | Ouyang, Chenxi; Meng, Changjiang; Li, Fei; Nie, Shanshan; Gong, Liying; Cao, Yu; Yuan, Hong; Feng, Zeying |
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| 組織名 | 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.;Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South;University, Changsha, Hunan, People's Republic of China.;Department of Critical Care Medicine, The Third Xiangya Hospital, Central South;Department of Cardiology, The Third Xiangya Hospital, Central South University,;Changsha, Hunan, People's Republic of China.;Clinical Trial Institution Office, Liuzhou Hospital of Guangzhou Women and;Children's Medical Center, Liuzhou, Guangxi, People's Republic of China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/38828024/ |
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