The APEX Trial: Effects of Allopurinol on Exercise Capacity, Coronary and Peripheral Endothelial Function and Natriuretic Peptides in Patients with Cardiac Syndrome X

Tiong Keng Lim, Awson Noman, Anna Maria J. Choy, Faisel Khan, Allan D. Struthers, Chim C. Lang (Lead / Corresponding author)

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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.

Original languageEnglish
Article numbere12311
Number of pages6
JournalCardiovascular Therapeutics
Issue number1
Early online date28 Oct 2017
Publication statusPublished - 10 Jan 2018


  • Allopurinol
  • Cardiac Syndrome X
  • Exercise
  • Oxidative stress
  • cardiac syndrome X
  • exercise
  • allopurinol
  • oxidative stress
  • Humans
  • Middle Aged
  • Male
  • Scotland
  • Brachial Artery/drug effects
  • Recovery of Function
  • Vasodilation/drug effects
  • Oxidative Stress/drug effects
  • Time Factors
  • Biomarkers/blood
  • Female
  • Exercise Tolerance/drug effects
  • Double-Blind Method
  • Treatment Outcome
  • Antioxidants/adverse effects
  • Allopurinol/adverse effects
  • Cross-Over Studies
  • Coronary Circulation/drug effects
  • Endothelium, Vascular/drug effects
  • Blood Flow Velocity
  • Coronary Vessels/drug effects
  • Aged
  • Microvascular Angina/blood
  • Natriuretic Peptide, Brain/blood

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)
  • Pharmacology


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