Impact of ALLopurInol on ENdothelial funCtion in diabEtic patients affected with coronary artery disease: ALLIENCE trial

Abstract

Allopurinol, a xanthine oxidase inhibitor, was shown to be useful in improving endothelial dysfunction in diabetic patients independently from their coronary status. We sought to assess the impact of allopurinol on endothelial function in diabetic patients with coronary artery disease (CAD) reputed to have severe endothelial dysfunction. We performed a simple-blind randomized trial enrolling patients with type 2 diabetes and CAD who underwent percutaneous coronary intervention. Patients were randomly assigned to either conventional optimal medical therapy alone (control group) or optimal medical therapy associated with high dose of allopurinol: 300 mg daily the first month then 600 mg daily the second month (allopurinol group). Endothelial function was assessed by flow-mediated dilation (FMD). The primary endpoint was the changes in FMD (Δ FMD) at 2 months. The secondary endpoints were the changes in endothelium-independent brachial dilation, and quality of life (QoL) as assessed by the Seattle Angina Questionnaire. A total of 64 patients (mean age 58.5 ± 8.3 years, 84.1% males) were randomly assigned to either allopurinol group ( n = 32) and control group ( n = 32). At baseline, FMD was comparable between the two groups ( P = 0.961). At 2 months, no significant change was observed in FMD between allopurinol group and control group ( P = 0.709). Regarding QoL, patients in allopurinol group showed better improvement in angina frequency ( P = 0.020) and disease perception ( P < 0.001) than controls. Subgroups analysis revealed that allopurinol was associated with significant improvement in FMD only in patients with poorly controlled diabetes (HBA1c > 8%) ( P = 0.010) and those with acid uric serum level ≤ 287 μmol/L ( P = 0.010) ( Fig. 1 ). Although allopurinol improved QoL (particularly angina frequency) in CAD diabetic patients, it did not improve the endothelial function except in those with poorly controlled diabetes and low acid uric serum level.