Saber-Moghaddam Niloufar, Nodeh Mohammad Moeini, Ghavami Vahid, Rahimi Hossein, Azimi Sajjad Ataei, Seddigh-Shamsi Mohsen, Kamandi Mostafa, Allahyari Abolghasem, Shariatmaghani Somayeh Sadat, Elyasi Sepideh, Arasteh Omid
Department of Clinical Pharmacy, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Hematology-Oncology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Jun;397(6):4355-4364. doi: 10.1007/s00210-023-02892-w. Epub 2023 Dec 14.
The development of invasive fungal infections (IFIs) is a serious complication in acute myeloid leukemia (AML) patients who undergo an induction to remission chemotherapy. Given the increased mortality in AML patients with IFI despite prophylaxis, we need to address this problem. Statins have traditionally been employed in clinical settings as agents for reducing lipid levels. Nonetheless, recent investigations have brought to light their antifungal properties in animals, as well as in vitro studies. The objective of this study was to assess the effectiveness of atorvastatin when added to the routine IFI prophylaxis regimen in patients diagnosed with AML. A randomized, multicenter, triple-blind study was conducted on 76 AML patients aged 18-70, who received either placebo or atorvastatin in addition to fluconazole. Patients were followed for 30 days in case of developing IFIs, patient survival, and atorvastatin- related adverse drug reactions. Data were analyzed with SPSS version 26.0. A level of significance of 0.05 was utilized as the threshold for all statistical tests. The data were analyzed by adjusting for the effect of age, regarding that there was a significant difference between the two groups, and showed that atorvastatin reduced the development of both probable and proven IFI (based on EORTC/MSGERC criteria) compared to placebo. IFI-free survival was also significantly better in the atorvastatin group. The incidence of developing aspergillosis did not differ between the two groups. No serious adverse events related to atorvastatin were observed. The present investigation has substantiated the antecedent in vitro and animal research on the fungicidal impact of statins and has suggested the need for additional research involving larger sample sizes and an extended duration of follow-up. Trial registration: This study was registered on the Iranian registry of clinical trials as IRCT20210503051166N1 (Date of confirmation 2021.05.03).
侵袭性真菌感染（IFI）的发生是接受诱导缓解化疗的急性髓系白血病（AML）患者的一种严重并发症。鉴于尽管进行了预防，IFI的AML患者死亡率仍有所增加，我们需要解决这个问题。他汀类药物传统上在临床环境中用作降低血脂水平的药物。尽管如此，最近的研究揭示了它们在动物以及体外研究中的抗真菌特性。本研究的目的是评估阿托伐他汀添加到确诊为AML患者的常规IFI预防方案中的有效性。对76名年龄在18至70岁的AML患者进行了一项随机、多中心、三盲研究，这些患者除了接受氟康唑外，还接受了安慰剂或阿托伐他汀。对患者进行了30天的随访，观察是否发生IFI、患者生存率以及与阿托伐他汀相关的药物不良反应。使用SPSS 26.0版对数据进行分析。所有统计检验均以0.05的显著性水平作为阈值。由于两组之间存在显著差异，因此在分析数据时对年龄的影响进行了调整，结果显示与安慰剂相比，阿托伐他汀减少了可能和确诊IFI（基于欧洲癌症研究与治疗组织/美国国立医学真菌学研究中心标准）的发生。阿托伐他汀组的无IFI生存率也显著更好。两组之间曲霉病的发生率没有差异。未观察到与阿托伐他汀相关的严重不良事件。本研究证实了先前关于他汀类药物杀菌作用的体外和动物研究，并表明需要进行更多涉及更大样本量和更长随访时间的研究。试验注册：本研究已在伊朗临床试验注册中心注册，注册号为IRCT20210503051166N1（确认日期2021.05.03）。
