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

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 randomized, placebo-controlled, double-blind trial of allopurinol (600 mg/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:

Seventy-two patients were randomized into the trial. Mean baseline urate was 362.2 ± 96.7 μmol/l. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared with placebo (LV mass -0.37 ± 6.08 versus -3.75 ± 3.89 g; P = 0.012). Oxidative stress markers (thiobarbituric acid reactive substances) were significantly higher in the allopurinol group versus placebo (0.26 ± 0.85 versus -0.34 ± 0.83 μmol/l; P = 0.007). Other markers of vascular function were not significantly different between the two groups.

CONCLUSION:

Treatment with high-dose allopurinol in normouricemic 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 because of an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.

• Authors: Christopher R Gingles, Ruth Symon, Stephen J Gandy, Allan D Struthers, Graeme Houston, Thomas M MacDonald, Chim C Lang, Peter T Donnan, Jacob George
• Journal: Journal of hypertension (J Hypertens) Vol. 37 Issue 12 Pg. 2481-2489 (12 2019) ISSN: 1473-5598 [Electronic] Netherlands
• PMID: 31268872 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Allopurinol

Topics

• Allopurinol (adverse effects, pharmacology, therapeutic use)
• Blood Pressure (drug effects)
• Double-Blind Method
• Essential Hypertension (complications)
• Heart Ventricles (drug effects, physiopathology)
• Humans
• Hypertrophy, Left Ventricular (complications, drug therapy)
• Oxidative Stress (drug effects)
• Pulse Wave Analysis