Heart of England NHS Foundation Trust, Birmingham, United Kingdom.
East & North Hertfordshire NHS Trust, Hertfordshire, United Kingdom; University of Hertfordshire, Hertfordshire, United Kingdom.
Pharmacol Ther. 2017 Apr;172:139-150. doi: 10.1016/j.pharmthera.2016.12.004. Epub 2016 Dec 2.
Epidemiological studies indicate that hyperuricaemia is an independent risk factor for cardiovascular disease. Alongside uric acid formation, increased xanthine oxidase activity also results in the formation of oxidative free radicals and superoxide particles. Oxidative stress significantly contributes to the development of cardiovascular disease, including endothelial cell dysfunction, atherosclerosis, vascular calcification and impaired myocardial energetics. Allopurinol, a competitive xanthine oxidase inhibitor, in addition to reducing serum uric acid levels, can act as a free radical scavenger. Although traditionally used for the management of gout, there has been renewed interest in the role of allopurinol in the management of cardiovascular disease. In this review, we summarise the role of the xanthine oxidase pathway in the generation of oxidative stress and evaluate the current body of evidence assessing the clinical effects of allopurinol in patients with cardiovascular disease. A number of small clinical studies have shown a beneficial effect of allopurinol in reducing ischemia-reperfusion injury in the setting of bypass surgery and coronary angioplasty. Additionally, studies in heart failure indicate a potential favourable effect of allopurinol on endothelial dysfunction, LV function and haemodynamic indices, particularly in those with raised serum uric acid levels. Whilst this cheap and readily available pharmacological option may offer a very cost effective therapeutic option, large-scale prospective studies are required to better delineate its role in reducing hard clinical end-points.
流行病学研究表明，高尿酸血症是心血管疾病的一个独立危险因素。除了尿酸生成增加外，黄嘌呤氧化酶活性的增加也会导致氧化自由基和超氧化物颗粒的形成。氧化应激是心血管疾病发展的重要因素，包括内皮细胞功能障碍、动脉粥样硬化、血管钙化和心肌能量代谢受损。别嘌醇是一种竞争性黄嘌呤氧化酶抑制剂，除了降低血尿酸水平外，还可以作为自由基清除剂。虽然别嘌醇传统上用于治疗痛风，但人们对其在心血管疾病治疗中的作用又产生了新的兴趣。在这篇综述中，我们总结了黄嘌呤氧化酶途径在氧化应激产生中的作用，并评估了目前评估别嘌醇在心血管疾病患者中临床效果的证据。一些小型临床研究表明，别嘌醇在旁路手术和冠状动脉成形术中减少缺血再灌注损伤方面有有益的效果。此外，心力衰竭研究表明，别嘌醇对内皮功能障碍、左心室功能和血液动力学指标有潜在的有利影响，特别是在血尿酸水平升高的患者中。虽然这种廉价且易于获得的药物选择可能提供一种非常有效的治疗选择，但需要进行大规模前瞻性研究来更好地阐明其在降低硬性临床终点方面的作用。
