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Xanthine Oxidase Inhibition For The Treatment Of Cardiovascular Disease: A Systematic Review and Meta-Analysis

机译：黄嘌呤氧化酶抑制治疗心血管疾病的系统评价和荟萃分析

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Background: Xanthine oxidase inhibition (XOI) reduces oxidative stress in the vasculature. Moreover it reduces uric acid levels, a risk factor for the development of cardiovascular disease. As such, XOI holds a potentially dual mechanism for the treatment of cardiovascular disease. Aims: Through systematic review, we sought to clarify the extent of available evidence that has evaluated the effect of XOI upon clinical or surrogate markers of cardiovascular disease and function in humans. Methods: A systematic search strategy was used to interrogate the Ovid Medline (1950-June Week 4 2010) and Embase (1980-2010 Week 25) databases, to identify relevant studies. Meta-analysis was planned for frequently studied endpoints. Results: Thirty-eight publications (reporting 40 studies) were identified. There was heterogeneity between studies in all aspects of study design, including the outcome measures of interest. Prospective assessment of surrogate markers predominated. Combined meta-analysis was feasible for three outcome parameters, with favorable modifications in each following xanthine oxidase inhibition: brachial artery flow mediated dilatation (five studies: XOI n = 75, control n = 69) increased by 2.50% (95% CI, 0.15-4.84); forearm blood flow responses to acetylcholine infusion (five studies: XOI n = 74, control n = 74) increased by 68.80 (95% CI, 18.70-118.90; percent change relative to noninfused control arm); circulating markers of oxidative stress (malondialdehyde, six studies: XOI n = 78, control n = 68) reduced by 0.56 nmol/mL (95% CI, 0.26-0.87). Conclusions: XOI improves endothelial function and circulating markers of oxidative stress in patients with, or at risk of, cardiovascular disease. Large prospective studies examining definitive end points are lacking but now appear indicated.
机译：背景：黄嘌呤氧化酶抑制（XOI）减少了脉管系统中的氧化应激。此外，它降低了尿酸水平，尿酸水平是发展心血管疾病的危险因素。因此，XOI拥有治疗心血管疾病的潜在双重机制。目的：通过系统的审查，我们试图阐明评估XOI对人的心血管疾病和功能的临床或替代指标的作用的现有证据的程度。方法：采用系统搜索策略对Ovid Medline（1950年-2010年6月4日）和Embase（1980-2010年第25周）数据库进行询问，以鉴定相关研究。计划对经常研究的终点进行荟萃分析。结果：确定了38篇出版物（报告40项研究）。研究设计各个方面的研究之间存在异质性，包括感兴趣的结果度量。前瞻性评估替代标记占主导。结合的荟萃分析对于三个结果参数是可行的，并在随后的黄嘌呤氧化酶抑制中进行了有利的修改：肱动脉血流介导的扩张（五个研究：XOI n = 75，对照组n = 69）提高了2.50％（95％CI，0.15） -4.84）;对乙酰胆碱输注的前臂血流反应（五项研究：XOI n = 74，对照组n = 74）增加了68.80（95％CI，18.70-118.90;相对于未输注对照组的百分比变化）;氧化应激的循环标志物（丙二醛，六项研究：XOI n = 78，对照n = 68）降低了0.56 nmol / mL（95％CI，0.26-0.87）。结论：XOI可改善患有心血管疾病或有心血管疾病风险的患者的内皮功能和氧化应激的循环指标。缺乏确定性终点的大型前瞻性研究，但现在看来已经表明。

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