Clinical Effects of Xanthine Oxidase Inhibitors in Hyperuricemic Patients

Abstract

This review aim is to critically resume the available clinical evidence supporting the treatment of chronic hyperuricemia with xanthine-oxidase inhibitor activity. For this reason, all of the studies published in English language from 2000 to August 2019 on uric acid-lowering drugs have been carefully reviewed. The terms “serum uric acid”, “xanthine oxidase”, “allopurinol”, “febuxostat”, and “topiroxostat” have been incorporated into an electronic search strategy, alone and in combinations, in both MEDLINE (National Library of Medicine, Bethesda, MD) and the Cochrane Register of Controlled Trials (The Cochrane Collaboration, Oxford, UK). Even if new urate lowering drugs seem of particular efficacy for acute treatment of refractory hyperuricemia, their use is supported by relatively small clinical evidence: On the contrary, large long-term clinical trials have clearly demonstrated that xanthine oxidase inhibitors (namely, allopurinol and febuxostat) are effective, safe and relatively well-tolerated in the most part of patients. They have been largely tested in elderly, in patients affected by crhonic diseases such as heart failure and cancer, and in patients taking a large number of drugs, confirming their safety profile. Recent data also show that they could exert some positive effects on vascular health, renal function and glucose metabolism. Their cost is also low. In conclusion, xanthine oxidase inhibitors remain the first choice uric acid lowering drug for chronic treatment.

Uric Acid and Hypertension: Prognostic Role and Guide for Treatment

“…Additionally, aldehyde dehydrogenase II (ALDH-2) polymorphisms have been associated with SUA levels and hypertension in genome wide association studies [ 86 ]. Other genetic polymorphisms that regulate SUA levels and associate with hypertension are XOR gene variants [ 85 , 87 , 88 ]. Of note, XOR is not only associated with increased SUA levels, but also with increased oxidative stress, which in turn may lead to the development of hypertension [ 87 , 88 ].…”

“…Other genetic polymorphisms that regulate SUA levels and associate with hypertension are XOR gene variants [ 85 , 87 , 88 ]. Of note, XOR is not only associated with increased SUA levels, but also with increased oxidative stress, which in turn may lead to the development of hypertension [ 87 , 88 ]. In contrast with the aforementioned studies, the genetic risk score developed using 30 gene variants responsible for SUA levels has been associated with lower BP values [ 84 ].…”

Therapeutic Strategies for the Treatment of Chronic Hyperuricemia: An Evidence-Based Update

“…Xanthine oxidase [XO] is the form of enzyme xanthine dehydrogenase responsible for converting hypoxanthine to UA in the purine metabolism pathway. During this process, there is the production of reactive oxygen species [ROS] [ 15 ]. When produced in excess, ROS reduces the synthesis of nitric oxide and lead to endothelial dysfunction [ 15 ].…”

“…During this process, there is the production of reactive oxygen species [ROS] [ 15 ]. When produced in excess, ROS reduces the synthesis of nitric oxide and lead to endothelial dysfunction [ 15 ]. A meta-analysis pooling data from 81 randomized clinical trials (RCTs) (N. 10684 included patients) showed that the xanthine oxidase inhibitors [XOIs] decreases the risk of total and serious cardiovascular events [Odds Ratio—OR = 0.60, p = 0.001 and OR = 0.64, p < 0.01 respectively] and onset/worsening hypertension [OR = 0.54, p = 0.002] in comparison with placebo.…”

Impact of Serum Uric Acid Lowering and Contemporary Uric Acid-Lowering Therapies on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis

“…The increased serum UA level has a similar prognostic impact in CVE and all-cause mortality, whether caused by increased generation or reduced excretion ( 12 ). Several studies have suggested that UA serves as an independent risk factor for CVD, that UA-lowering medicines improved cardiovascular outcomes, and that lowering the UA level is one of the most effective methods for reducing cardiovascular risk ( 1 , 13 ). However, both UA-lowering agents and very low levels of UA are threats to cardiovascular health.…”