Cardiovascular safety of febuxostat. Analysis of the CARES study
Gout is associated with the high frequency of comorbidities, among which there are cardiovascular disease and kidney diseases. In this case, cardiovascular mortality rates are in the first place among the causes of death in patients with gout and exceed the death rates in the population. This may be associated with the main signs of gout, such as a high serum uric acid (UA) level and its related chronic inflammation. Drug correction of hyperuricemia is the mainstay of gout therapy and it is supposed to be able to neutralize the negative effect of UA on the risk of its associated adverse events. Xanthine oxidase inhibitors (allopurinol and febuxostat) are first-line urate-lowering agents. Their effect on UA levels, comorbidities, long-term outcomes (including overall and cardiovascular mortality, development and progression of chronic kidney disease), and occurrence of adverse reactions is studied in large-scale studies, the results of which may affect the strategy of such therapy. The paper discusses the advantages and disadvantages of the CARES (Gout and Cardiovascular Morbidities) study that has compared the cardiovascular safety of allopurinol and febuxostat. The findings suggest that there is no substantial difference in the frequency of cardiovascular events with febuxostat and allopurinol, but at the same time these demonstrate a high risk for cardiovascular and overall mortality in the febuxostat group. Analysis of this paper cannot conclude that there is a greater cardiovascular risk with therapy with febuxostat; however, it shows that when compared with allopurinol, this risk may be higher. A more detailed study of this issue is required after obtaining the results of already started and planned investigations comparing the effects of allopurinol and febuxostat on the risk of adverse cardiovascular events in patients with asymptomatic hyperuricemia.