Allopurinol to reduce CAD mortality?

High-dose allopurinol could reduce future cardiovascular mortality in coronary artery disease (CAD), “over and above existing optimum therapy”, according to a study published recently in the Journal of the American College of Cardiology.¹

Authors led by Dr Narasimharajapura S Rajendra, University of Dundee, UK, conducted a randomised crossover study on 80 patients with CAD, comparing allopurinol (600 mg/day) with placebo. Endothelial function was assessed by forearm venous occlusion plethysmography, flow-mediated dilatation, and pulse wave analysis. Vascular oxidative stress (OS) was assessed by intra-arterial co-infusion of vitamin C and acetylcholine.

They found that, in optimally treated CAD patients, allopurinol significantly improved endothelium-dependent vasodilatation compared with placebo, by both forearm venous occlusion plethysmography (p = 0.006) and flow-mediated dilatation (p < 0.001). Vascular OS was completely abolished by allopurinol.

The authors assert that allopurinol could reduce CV deaths in CAD, “especially because OS is thought to contribute to plaque instability and also because allopurinol is already associated with a significantly better total mortality”.

Patient undergoes forearm venous occlusion plethysmography

In an accompanying editorial,² Dr Peter Stone discusses the anti-ischaemic effects of the drug, saying: “Although it is tantalising to speculate that the marked effect of allopurinol to reduce vascular oxidative stress will translate into clinical vascular protection and a role in routine secondary prevention, it is a substantial leap at this time to assume that the observed benefit of allopurinol on endothelium-dependent vasomotion will translate into an improvement in the fundamental pathobiology of atherosclerosis”.

“Mortality in CAD patients is primarily related to plaque rupture or erosion, leading to superimposed thrombus formation and precipitation of an acute coronary syndrome, and not to endothelial dysfunction and abnormal coronary vasomotion. Although allopurinol reduces vascular oxidative stress, its therapeutic effects on the local behavior within advanced, complicated atherosclerotic plaque need to be investigated.”

References

1 Rajendra NS, Ireland S, George J, Belch JJF, Lang CC, Struthers AD. Mechanistic Insights Into the Therapeutic Use of High-Dose Allopurinol in Angina Pectoris. JACC 2011;58:820–8.

2 Stone, PH. Allopurinol: a new anti-ischemic role for an old drug. JACC 2011;58:829–30.