Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension

Christopher Gingles, Ruth Symon, Stephen Gandy, Allan Struthers, Graeme Houston, Thomas MacDonald, Chim Lang, Peter Donnan, Jacob George (Lead / Corresponding author)

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5 Citations (Scopus)
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Abstract

Objectives: Previous studies have demonstrated that high dose allopurinol is able to regress Left Ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well- controlled blood pressure but without established cardiovascular disease.

Methods: We conducted a mechanistic proof-of-concept randomised, placebo controlled, double-blind trial of allopurinol (600mg/day) versus placebo on LV mass regression. Duration of treatment was 12 months. LV mass regression was assessed by Cardiac Magnetic Resonance. Secondary outcomes were changes in endothelial function (flow mediated dilatation), arterial stiffness (pulse wave velocity) and biomarkers of oxidative stress.

Results: 72 patients were randomised into the trial. Mean baseline urate was 362.2 ± 96.7umol/L. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared to placebo (LV mass -0.37 ± 6.08 g vs -3.75 ± 3.89 g; p=0.012). Oxidative stress markers (Thiobarbituric acid reactive substances) were significantly higher in the allopurinol group vs placebo (0.26 ± 0.85uM vs -0.34 ± 0.83uM; p=0.007). Other markers of vascular function were not significantly different between the two groups.

Conclusions: Treatment with high dose allopurinol in normo-uricemic controlled hypertensive patients and LV hypertrophy is detrimental. It results in reduced LV mass regression and increased oxidative stress over a 12-month period. This may be due to an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.
Original languageEnglish
Pages (from-to)2481-2489
Number of pages9
JournalJournal of Hypertension
Volume37
Issue number12
Early online date1 Jul 2019
DOIs
Publication statusPublished - Dec 2019

Keywords

  • Uric acid
  • oxidative stress
  • hypertension

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