Department of Pharmacology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Cardiovasc Ther. 2018 Aug;36(4):e12432. doi: 10.1111/1755-5922.12432. Epub 2018 May 24.
Oxidative stress and endothelial dysfunction are two inter-related conditions commonly seen in patients with cardiovascular risk factors. The enzyme, xanthine oxidase, is an important contributor to these phenomena but to a variable degree in different patient populations. This meta-analysis will summarize the effect of allopurinol, an established xanthine oxidase inhibitor, on endothelial function among patients with different comorbidities.
Medline Complete, PubMed, ProQuest, ClinicalKey, Wiley Online Library, and Cochrane Central Register of Controlled Trials were searched till July 29, 2017. Meta-analysis was planned for randomized controlled trials (RCTs) that investigated allopurinol effects on endothelial function. A random effect model was used to calculate the standardized mean difference (with 95% confidence intervals: CI) as an estimate of effect size. Heterogeneity was quantified by four types of information: Q statistics, I statistic, Tau-squared (T ), and Tau (T).
Thirty eligible studies were identified; 12 were included in the final analysis and subdivided among 3 patient's groups: patients with chronic heart failure (CHF; 197 patients), patients with chronic kidney disease (CKD; 183 patients), and patients with type 2 diabetes mellitus (DM; 170 patients). Allopurinol was found to have a statistically significant benefit on endothelial function in patients with CHF and CKD but not in type 2 DM. The standardized mean differences and CI in the three patient's groups were 0.776 (0.429, 1.122), 0.350 (0.009, 0.690), and 1.331 (-0.781, 3.444), respectively.
Allopurinol has an antioxidant property that might partially reverse endothelial dysfunction in patients with certain comorbidities. The importance of this property and the magnitude of the beneficial effect are likely to be related to the relative contribution of xanthine oxidase into the oxidative stress associated with different underlying pathologies.
氧化应激和内皮功能障碍是心血管危险因素患者常见的两种相互关联的情况。黄嘌呤氧化酶是导致这些现象的重要因素，但在不同的患者群体中程度不同。本荟萃分析将总结黄嘌呤氧化酶抑制剂别嘌呤醇对不同合并症患者内皮功能的影响。
检索 Medline Complete、PubMed、ProQuest、ClinicalKey、Wiley Online Library 和 Cochrane 对照试验中心注册库，检索时间截至 2017 年 7 月 29 日。荟萃分析计划纳入研究别嘌呤醇对内皮功能影响的随机对照试验（RCT）。采用随机效应模型计算标准化均数差（置信区间：CI）作为效应大小的估计值。采用 Q 统计量、I 统计量、Tau 平方（T ）和 Tau（T）四种信息来量化异质性。
确定了 30 项符合条件的研究，其中 12 项研究纳入最终分析，并分为 3 组患者：慢性心力衰竭（CHF；197 例）、慢性肾脏病（CKD；183 例）和 2 型糖尿病患者（DM；170 例）。结果发现，别嘌呤醇对 CHF 和 CKD 患者的内皮功能有统计学意义上的益处，但对 2 型 DM 患者没有益处。三组患者的标准化均数差异和 CI 分别为 0.776（0.429，1.122）、0.350（0.009，0.690）和 1.331（-0.781，3.444）。
别嘌呤醇具有抗氧化特性，可能部分逆转某些合并症患者的内皮功能障碍。这种特性的重要性及其有益效果的程度可能与黄嘌呤氧化酶在不同潜在病理相关的氧化应激中的相对贡献有关。
