Department of Medical and Surgical Sciences, University of Bologna, Via Albertoni 15, Bologna, Italy.
Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy.
Drugs. 2018 Jan;78(1):99-109. doi: 10.1007/s40265-017-0839-5.
Uric acid (UA), the final product of purine catabolism, may be associated with an increased risk of cardiovascular disease.
The aim of this meta-analysis of randomized placebo-controlled trials was to evaluate whether lowering serum UA (SUA) levels with allopurinol is associated with improved flow-mediated dilation (FMD), a validated marker of early vascular damage.
A literature search was carried out from inception until 20 June 2017. Meta-analysis was performed using an inverse variance-weighted, random-effects model with standardized mean difference (SMD) as the effect size estimate.
Meta-analysis of data from the ten eligible randomized controlled trials (RCTs), with 670 subjects, suggested a significant increase in FMD following allopurinol treatment (weighted mean difference [WMD] 1.79%, 95% confidence interval [CI] 1.01-2.56, p < 0.001; I : 86.77%). The effect size was robust and remained significant after omission of each single study. Subgroup analyses of RCTs based on the administered dose or duration of treatment did not reveal any significant impact of these variables on FMD change. Nor was a significant association found between allopurinol-induced changes in SUA levels and FMD (slope 0.46, p = 0.253), whereas baseline FMD significantly influenced the degree of FMD improvement following allopurinol treatment (slope 0.52, p = 0.022). Nitroglycerin-mediated dilation was not altered by allopurinol treatment (WMD 0.88%, 95% CI - 1.15-2.91, p = 0.395; I : 80.88%).
This meta-analysis of available RCTs suggests a significant benefit from allopurinol intake in increasing FMD in humans, independent of its effect on SUA levels.
尿酸（UA）是嘌呤代谢的终产物，可能与心血管疾病风险增加有关。
本荟萃分析旨在评估别嘌呤醇降低血清尿酸（SUA）水平是否与血流介导的扩张（FMD）改善相关，后者是早期血管损伤的有效标志物。
检索从建库至 2017 年 6 月 20 日的文献。采用逆方差加权、随机效应模型进行荟萃分析，以标准化均数差（SMD）作为效应量估计。
对 10 项符合条件的随机对照试验（RCT），670 例患者的数据进行荟萃分析，结果表明别嘌呤醇治疗后 FMD 显著增加（加权均数差 [WMD] 1.79%，95%置信区间 [CI] 1.01-2.56，p<0.001；I²=86.77%）。剔除单项研究后，该效应大小仍具有统计学意义且稳健。基于给予的剂量或治疗持续时间的 RCT 亚组分析并未发现这些变量对 FMD 变化有任何显著影响。别嘌呤醇诱导的 SUA 水平变化与 FMD 之间也无显著相关性（斜率 0.46，p=0.253），而基线 FMD 显著影响别嘌呤醇治疗后 FMD 的改善程度（斜率 0.52，p=0.022）。硝酸甘油介导的扩张不受别嘌呤醇治疗的影响（WMD 0.88%，95%CI -1.15-2.91，p=0.395；I²=80.88%）。
本荟萃分析纳入的 RCT 表明，别嘌呤醇可增加 FMD，这与 SUA 水平的影响无关。
