Mechanistic Insights Into the Therapeutic Use of High-Dose Allopurinol in Angina Pectoris Full Text
JACC - Journal of the American College of Cardiology, 08/09/2011
Rajendra NS et al. – This study demonstrates that, in optimally treated coronary artery disease (CAD) patients, high–dose allopurinol profoundly reduces vascular tissue oxidative stress (OS) and improves 3 different measures of vascular/endothelial dysfunction. The former effect on OS might underpin the anti–ischemic effect of allopurinol in CAD. Both effects (on OS and endothelial dysfunction) increase the likelihood that high–dose allopurinol might reduce future cardiovascular mortality in CAD, over and above existing optimum therapy.Methods
- A randomized, double–blind, placebo–controlled, crossover study was conducted in 80 patients with CAD, comparing allopurinol (600 mg/day) with placebo.
- Endothelial function was assessed by forearm venous occlusion plethysmography, flow–mediated dilation, and pulse wave analysis.
- Vascular OS was assessed by intra–arterial co–infusion of vitamin C and acetylcholine.
- Compared with placebo, allopurinol significantly improved endothelium–dependent vasodilation, by both forearm venous occlusion plethysmography (93 ± 67% vs. 145 ± 106%, p = 0.006) and flow–mediated dilation (4.2 ± 1.8% vs. 5.4 ± 1.7%, p < 0.001).
- Vascular oxidative stress was completely abolished by allopurinol. Central augmentation index improved significantly with allopurinol (2.6 ± 7.0%, p < 0.001) but not with placebo.