TamehriZadeh Seyed Saeed, Khalaji Mahla, Tajdari Mobina, Mavaddat Helia, Szmit Sebastian, Lashgari Naser-Aldin, Roudsari Nazanin Momeni, Abbasi-Kashkoli Hamed, Banach Maciej, Abdolghaffari Amir Hossein
Medical School, University of Western Australia, Perth, Australia.
Faculty of Pharmacy, Iran University of Medical Sciences (IUMS), Tehran, Iran.
Cardiovasc Toxicol. 2025 Jul 10. doi: 10.1007/s12012-025-10030-6.
This study aims to evaluate the potential role of statins in preventing doxorubicin-induced cardiotoxicity. With the rising number of cancer survivors and the persistent use of doxorubicin in treatment protocols, there is an urgent need for effective cardioprotective strategies to mitigate long-term cardiovascular complications. Statins, widely used for cardiovascular disease prevention, offer a promising repurposing opportunity due to their pleiotropic effects. A comprehensive review of existing animal and clinical studies was conducted to assess the cardioprotective effects of statins. Key mechanisms such as reduction of oxidative stress, inflammation, and apoptosis were examined, alongside current clinical evidence evaluating their use in patients receiving doxorubicin. Preclinical studies consistently demonstrate that statins significantly reduce doxorubicin-induced cardiotoxicity by modulating multiple cellular pathways involved in oxidative stress, inflammation, and programmed cell death. These findings highlight statins' multifaceted mechanisms of action in protecting cardiac tissue. Numerous observational studies have shown that statin therapy may reduce the incidence and severity of doxorubicin-induced cardiotoxicity, reflected by less decline in left ventricular ejection fraction and a lower risk of heart failure in those receiving statins, but results from randomized controlled trials remain inconsistent. Given the growing burden of cancer therapy-related cardiovascular disease and the established safety profile of statins, further large-scale clinical trials are warranted to confirm their protective role, determine optimal dosing strategies, and facilitate integration into oncology practice. Establishing their utility could improve long-term outcomes for cancer patients vulnerable to cardiotoxicity.
本研究旨在评估他汀类药物在预防阿霉素诱导的心脏毒性方面的潜在作用。随着癌症幸存者数量的增加以及阿霉素在治疗方案中的持续使用，迫切需要有效的心脏保护策略来减轻长期心血管并发症。他汀类药物广泛用于预防心血管疾病，由于其多效性作用，提供了一个有前景的重新利用机会。对现有的动物和临床研究进行了全面综述，以评估他汀类药物的心脏保护作用。研究了诸如减少氧化应激、炎症和细胞凋亡等关键机制，以及目前评估其在接受阿霉素治疗患者中使用情况的临床证据。临床前研究一致表明，他汀类药物通过调节参与氧化应激、炎症和程序性细胞死亡的多种细胞途径，显著降低阿霉素诱导的心脏毒性。这些发现突出了他汀类药物在保护心脏组织方面的多方面作用机制。大量观察性研究表明，他汀类药物治疗可能降低阿霉素诱导的心脏毒性的发生率和严重程度，表现为接受他汀类药物治疗者左心室射血分数下降较少以及心力衰竭风险较低，但随机对照试验的结果仍不一致。鉴于癌症治疗相关心血管疾病的负担日益加重以及他汀类药物已确立的安全性，有必要进行进一步的大规模临床试验，以确认其保护作用，确定最佳给药策略，并促进其纳入肿瘤学实践。确定它们的效用可以改善易发生心脏毒性的癌症患者的长期预后。
