Gout lessons from 2018: CARES, a direct comparison of febuxostat vs allopurinol, and CANTOS, IL1 blocker for cardiovascular risk minimisation

In the Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) trial conducted by White et al. (March 29 issue from NEJM), all-cause mortality and cardiovascular mortality are found to be higher among patients randomly assigned to febuxostat compared to allopurinol, but significant flaws are a clear lack of treat to target strategy with more powered treatment in the febuxostat arm, dysbalance with cardiovascular risk factors selectively in again the febuxostat arm, and discontinuation of the trial regimen in over 50% of patients with discontinuation of follow-up in about 45%. With these flaws, conclusions such as febuxostat-associated higher mortality are potentially if not probably incorrect, and thus febuxostat to be used not as first-line therapy may well be an invalid consequence? The paper here describes potential lessons to be taken.