This review aims to critically present the available clinical evidence supporting the treatment of chronic
hyperuricemia with
xanthine oxidase inhibitors. For this reason, the studies published on
uric acid (UA)-lowering drugs in the English language from 2000 to August 2019 have been carefully reviewed. The terms "serum
uric acid," "
xanthine oxidase," "
allopurinol," "
febuxostat," and "
topiroxostat" were 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 demonstrated that
xanthine oxidase inhibitors (XOIs, namely,
allopurinol and
febuxostat) are effective, safe, and relatively well-tolerated in most of the patients. They have mainly been tested in the elderly, in patients affected by
chronic 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, XOIs remain the first choice of UA-lowering drug for chronic treatment.