The APEX trial: Effects of allopurinol on exercise capacity, coronary and peripheral endothelial function, and natriuretic peptides in patients with cardiac syndrome X
The APEX trial: Effects of allopurinol on exercise capacity, coronary and peripheral endothelial function, and natriuretic peptides in patients with cardiac syndrome X
复制标题
APEX 试验：别嘌呤醇对心脏 X 综合征患者运动能力、冠状动脉和外周内皮功能以及利尿钠肽的影响
作者：
T. Lim;Awson Noman;A. Choy;F. Khan;A. Struthers;C. Lang
内皮功能障碍和氧化应激在心脏X综合征发病机制中的作用最近被认识到。别嘌醇此前已被证明可以改善内皮功能障碍，减少氧化应激负担，并提高心肌效率。在这项“概念验证”研究中，我们研究了别嘌醇对心脏X综合征患者的运动能力、冠状动脉和外周血管内皮功能以及血清B型利钠肽(BNP：心功能和心肌缺血的标志)的影响。
方法和结果
该研究是一项随机、双盲、安慰剂对照的交叉试验。19名心脏X综合征患者(平均年龄59岁±10岁，11名女性和8名男性)被随机分成两组，接受为期6周的别嘌醇(600 mg/天)或安慰剂治疗。在4周的洗涤期后，他们被交叉到另一只手臂上。在基线和治疗后测量的结果是通过Bruce方案运动平板试验得出的最大运动时间(ET)，血清BNP测量，通过测量左前降支血流速度对腺苷的反应来评估冠脉血流储备(CFR)，以及血流介导的臂动脉血管扩张(FMD)。与安慰剂相比，别嘌醇显著降低了血清尿酸水平(-48±0.24%比1.9±0.11%，P<0.01)。别嘌醇组和安慰剂组的最大ET、CFR和FMD无显著差异。然而，与安慰剂相比，别嘌醇有降低血清BNP的趋势(-8%[四分位数范围-22%至65%]比44%[四分位数范围-18%至140%；P=10.07]。
结论
在心脏综合征X患者中，大剂量别嘌醇并没有改善运动能力，也没有改善冠状动脉或外周血管内皮功能。
The role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X has recently been recognized. Allopurinol has previously been shown to improve endothelial dysfunction, reduce oxidative stress burden, and improve myocardial efficiency. In this "proof of concept" study, we investigated the effect of allopurinol on exercise capacity, coronary and peripheral endothelial function, and serum B-type natriuretic peptide (BNP: a marker of cardiac function and myocardial ischemia) in patients with cardiac syndrome X.
METHODS AND RESULTS
This study was a randomized, double-blind, placebo-control crossover trial. Nineteen patients (mean age 59 ± 10 years, 11 women and 8 men) with cardiac syndrome X were randomized to a 6-week treatment with either allopurinol (600 mg/day) or placebo. After 4 weeks of washout period, they were crossed over to the other arm. Outcomes measured at baseline and after treatment were maximum exercise time (ET) derived from Bruce protocol exercise treadmill test, serum BNP measurement, coronary flow reserve (CFR) as assessed by measuring the response of flow velocity in the left anterior descending artery to adenosine, and flow-mediated vasodilatation of the brachial artery (FMD). Allopurinol significantly reduced serum uric acid levels when compared with placebo (-48 ± 24% vs 1.9 ± 11%, P < .001). There was no significant difference in maximum ET, CFR, and FMD between allopurinol and placebo. However, there was a trend that allopurinol reduced serum BNP when compared to placebo (-8% [interquartile range -22% to 65%] vs 44% [interquartile range -18% to 140%]; P = .07).
CONCLUSION
In patients with cardiac syndrome X, high-dose allopurinol did not improve exercise capacity, and coronary or peripheral endothelial function.