Impact of allopurinol on endothelial function in diabetic patients affected with coronary artery disease: Results from the randomized ALLIENCE trial

Title : Impact of allopurinol on endothelial function in diabetic patients affected with coronary artery disease: Results from the randomized ALLIENCE trial

Abstract:

Background: It is well known that diabetic patients have increased oxidative stress with different degrees of endothelial dysfunction. Although studies have demonstrated the benefit of the use of high dose of Allopurinol in improving the endothelium function, its impact on diabetic patients suffering from coronary artery disease (CAD) still unclear.

Methods: We performed a simple-blind randomized trial enrolling patients with type 2 diabetes and CAD who underwent percutaneous coronary intervention (PCI). Patients were randomly assigned to either conventional optimal medical therapy (OMT) alone (control group) or OMT associated with high dose of Allopurinol (300mg/day the first month then 600 mg/day the second month) (Allopurinol group). The primary endpoint was the changes in endothelium-dependent « flow mediated dilation » (FMD) at 2 months. The secondary endpoints were the changes in endothelium-independent brachial dilation, quality of life (QoL) as assessed by Seattle Angina Questionnaire (SAQ), and major adverse cardiac events (MACE) occurrence at 2 months. The study was registered on clinicaltrials.gov: NCT03385135. Results: From September 2017 to April 2018, a total of 63 patients (mean age 58.5±8.3 years, 84.1% males) were included into the study, and randomly assigned to either Allopurinol group (N=32) and control group (N=31). No differences in clinical characteristics were observed between the two groups (all p=NS). At baseline, FMD was comparable between the two groups (Allopurinol:3.22 [inter-quartile interval (IQI) 0.27-8.19] %, controls:3.52 [IQI 1.22-5.41] %, p=0.961). At 2 months, no significant difference was observed in FMD between Allopurinol group (3.87 [IIQ 2.76-8.69]) and control group (3.51 [IIQ 2.75-7.69]) (p=0.598). Similarly, no significant improvement in endothelium-independent brachial dilation was found in Allopurinol group in comparison with controls (p=0.478). Regarding QoL, at 2 months, patients in Allopurinol group showed better improvement in angina frequency (p=0.020) and disease perception (p 8%) (? FMD +2.37 [IIQ -0.39-6.02] % vs. +0.13 [IIQ -2.76-2.55] %, p=0.010), and those with acid uric serum level ≤ 287 µmol/l (? FMD +4.7 [IIQ 2.21-8.12] % vs. -0.16 [IIQ -2.58-3.56], p=0.010).

Conclusion: Although Allopurinol improved QoL (particularly angina frequency) in CAD diabetic patients, it did not improve significantly the endothelial function, except in those with poorly controlled diabetes and those with relatively low acid uric serum level.

Audience Take Away:

• The physiopathology of endothelial dysfunction particularly in patients affected with diabetes and CAD.

• The mechanism of allopurinol impact on endothelial function and its classification as anti-anginal drug.

• The impact of allopurinol on the endothelial dysfunction in diabetic CAD patients

• The impact of allopurinol on the Qol in diabetic CAD patients

• Which diabetic patient would take more benefit from allopurinol prescription in terms of improvement of endothelial dysfunction

Biography:

Dr. Boukhris is an interventional cardiologist specialized in complex high-risk (CHIP) PCI and strucutural interventions. After obtaining his MD degree and specialist diploma in Cardiology at the Faculty of Medicine of Tunis, University of Tunis El Manar (Tunisia), he pursued further training with a fellowship in Interventional Cardiology at Cannizzaro Hospital, University of Catania (Italy) under the supervision of Prof Alfredo R. Galassi (founder member and past president of the EuroCTO Club).

In 2017, Dr Boukhris has become Assistant Professor in Cardiology at the Faculty of Medicine of Tunis, University of Tunis El Manar (Tunisia).

In 2019, he granted a second 2-year fellowship at Centre Hospitalier de l'Université de Montréal (CHUM) within both programs of the Adult Interventional Cardiology program of the Université de Montréal and the Royal College of Physians and Surgeons of Canada.

In his practice Dr Boukhris performs coronary interventions including left main stenting, complex bifurcation stenting, bypass graft PCI, antegrade CTO PCI, intravascular imaging (IVUS, OCT), FFR, rotational atherectomy, in addition to structural interventions including TAVR, and percutaneous closure of PFO, ASD and LAAD.

His main research interests are focused on CTO PCI, TAVR, LAA closure, application of 3-D engineering modalities to the plannification of structural interventions.

Dr. Boukhris has published over 80 peer-reviewed articles and has presented over 60 times at international congresses. He has also won several awards. He is actually reviewer and member of the editorial board of several renowned cardiology Journals.