Golledge Jonathan, Norman Paul E, Murphy Michael P, Dalman Ronald L
Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia.
School of Surgery, University of Western Australia, Perth, Western Australia, Australia.
J Vasc Surg. 2017 Jan;65(1):225-233. doi: 10.1016/j.jvs.2016.08.003. Epub 2016 Sep 15.
This review describes ongoing efforts to develop a medical therapy to limit abdominal aortic aneurysm (AAA) growth.
Data from animal model studies, human investigations, and clinical trials are described.
Studies in rodent models and human samples have suggested a number of potential targets for slowing or halting AAA growth. A number of clinical trials are now examining the value of medications targeting some of the pathways identified. These trials have a number of challenges, including identifying medications safe to use in older patients with multiple comorbidities, developing accurate outcome assessments, and minimizing the dropout of patients during the trials. Three recent trials have reported no benefit of the antibiotic doxycycline, a mast cell inhibitor, an angiotensin-converting enzyme inhibitor, or a calcium channel blocker in limiting AAA growth. A number of other trials examining angiotensin receptor blockers, cyclosporine, and an antiplatelet agent are currently underway.
Further refinement of drug discovery pathways and testing paradigms are likely needed to develop effective nonsurgical therapies for AAA.
本综述描述了为开发一种限制腹主动脉瘤(AAA)生长的医学疗法而正在进行的努力。
描述了来自动物模型研究、人体研究和临床试验的数据。
啮齿动物模型和人体样本研究提示了一些减缓或阻止AAA生长的潜在靶点。目前一些临床试验正在检验针对某些已确定途径的药物的价值。这些试验面临诸多挑战,包括确定对患有多种合并症的老年患者安全的药物、开发准确的结果评估方法以及尽量减少试验期间患者的退出。最近三项试验报告称,抗生素强力霉素、肥大细胞抑制剂、血管紧张素转换酶抑制剂或钙通道阻滞剂在限制AAA生长方面并无益处。目前正在进行其他多项试验,检验血管紧张素受体阻滞剂、环孢素和一种抗血小板药物。
可能需要进一步完善药物研发途径和测试模式,以开发出有效的AAA非手术疗法。