Clinical Research
Coronary Artery Disease
High-Dose Allopurinol Reduces Left Ventricular Mass in Patients With Ischemic Heart Disease

https://doi.org/10.1016/j.jacc.2012.09.066Get rights and content
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Objectives

This study sought to ascertain if high-dose allopurinol regresses left ventricular mass (LVM) in patients with ischemic heart disease (IHD).

Background

LV hypertrophy (LVH) is common in patients with IHD including normotensive patients. Allopurinol, a xanthine oxidase inhibitor, has been shown to reduce LV afterload in IHD and may therefore also regress LVH.

Methods

A randomized, double-blind, placebo-controlled, parallel group study was conducted in 66 patients with IHD and LVH, comparing 600 mg/day allopurinol versus placebo therapy for 9 months. The primary outcome measure was change in LVM, assessed by cardiac magnetic resonance imaging (CMR). Secondary outcome measures were changes in LV volumes by CMR, changes in endothelial function by flow-mediated dilation (FMD), and arterial stiffness by applanation tonometry.

Results

Compared to placebo, allopurinol significantly reduced LVM (allopurinol −5.2 ± 5.8 g vs. placebo −1.3 ± 4.48 g; p = 0.007) and LVM index (LVMI) (allopurinol −2.2 ± 2.78 g/m2 vs. placebo −0.53 ± 2.5 g/m2; p = 0.023). The absolute mean difference between groups for change in LVM and LVMI was −3.89 g (95% confidence interval: −1.1 to −6.7) and −1.67 g/m2 (95% confidence interval: −0.23 to −3.1), respectively. Allopurinol also reduced LV end-systolic volume (allopurinol −2.81 ± 7.8 mls vs. placebo +1.3 ± 7.22 mls; p = 0.047), improved FMD (allopurinol +0.82 ± 1.8% vs. placebo −0.69 ± 2.8%; p = 0.017) and augmentation index (allopurinol −2.8 ± 5.1% vs. placebo +0.9 ± 7%; p = 0.02).

Conclusions

High-dose allopurinol regresses LVH, reduces LV end-systolic volume, and improves endothelial function in patients with IHD and LVH. This raises the possibility that allopurinol might reduce future cardiovascular events and mortality in these patients. (Does a Drug Allopurinol Reduce Heart Muscle Mass and Improve Blood Vessel Function in Patients With Normal Blood Pressure and Stable Angina?; ISRCTN73579730)

Key Words

allopurinol
ischemic heart disease
oxidative stress
ventricular hypertrophy

Abbreviations and Acronyms

AIx
augmentation index
BNP
B-type natriuretic peptide
BP
blood pressure
CMR
cardiac magnetic resonance
FMD
flow-mediated dilation
IHD
ischemic heart disease
LVH
left ventricular hypertrophy
LVM
left ventricular mass
LVMI
left ventricular mass index
PWV
pulse wave velocity

Cited by (0)

This work was financially supported by the Medical Research Council (UK) G0701592. Dr. Struthers has served as a consultant to Pfizer, Merck, and Roche. Dr. Struthers and the University of Dundee have applied for a patent on the use of xanthine oxidase inhibitors to treat angina pectoris. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.