High-dose allopurinol reduces left ventricular mass in patients with ischemic heart disease

Abstract

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/m(2) vs. placebo -0.53 ± 2.5 g/m(2); 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/m(2) (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).