Mangoni Arduino A, Tommasi Sara, Zinellu Angelo, Sotgia Salvatore, Carru Ciriaco, Piga Matteo, Erre Gian Luca
Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, Australia.
Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Drugs Context. 2018 Nov 14;7:212557. doi: 10.7573/dic.212557. eCollection 2018.
About 20% of patients with a history of atherosclerotic cardiovascular disease will experience further cardiovascular events despite maximal pharmacological treatment with cardioprotective drugs. This highlights the presence of residual cardiovascular risk in a significant proportion of patients and the need for novel, more effective therapies. These therapies should ideally target different pathophysiological pathways involved in the onset and the progression of atherosclerosis, particularly the inflammatory and immune pathways. Methotrexate is a first-line disease-modifying antirheumatic drug that is widely used for the management of autoimmune and chronic inflammatory disorders. There is some and evidence that methotrexate might exert a unique combination of anti-inflammatory, blood pressure lowering, and vasculoprotective effects. Pending the results of large prospective studies investigating surrogate end-points as well as morbidity and mortality, repurposing methotrexate for cardiovascular risk management might represent a cost-effective strategy with immediate public health benefits. This review discusses the current challenges in the management of cardiovascular disease; the available evidence on the effects of methotrexate on inflammation, blood pressure, and surrogate markers of arterial function; suggestions for future research directions; and practical considerations with the use of methotrexate in this context.
约20%有动脉粥样硬化性心血管疾病病史的患者，尽管使用心脏保护药物进行了最大程度的药物治疗，仍会发生进一步的心血管事件。这凸显了相当一部分患者存在残余心血管风险，以及对新型、更有效治疗方法的需求。理想情况下，这些治疗方法应针对动脉粥样硬化发生和发展过程中涉及的不同病理生理途径，尤其是炎症和免疫途径。甲氨蝶呤是一种一线改善病情抗风湿药物，广泛用于自身免疫性和慢性炎症性疾病的治疗。有一些证据表明，甲氨蝶呤可能具有抗炎、降压和血管保护作用的独特组合。在等待大型前瞻性研究调查替代终点以及发病率和死亡率结果期间，将甲氨蝶呤重新用于心血管风险管理可能是一种具有直接公共卫生效益的经济有效策略。本综述讨论了心血管疾病管理中的当前挑战；关于甲氨蝶呤对炎症、血压和动脉功能替代标志物影响的现有证据；对未来研究方向的建议；以及在这种情况下使用甲氨蝶呤的实际考虑因素。
