Febuxostat Use and Risks of Cardiovascular Disease Events, Cardiac Death, and All-cause Mortality: Metaanalysis of Randomized Controlled Trials

Objective. To assess whether febuxostat use increases the risk of developing cardiovascular (CV) events, cardiac death, and all-cause mortalities. Methods. The relevant literature was searched in several databases including MEDLINE (PubMed, January 1, 1966-February 29, 2020), Web of Science, EMBASE (January 1, 1974-February 29, 2020), ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials. Manual searches for references cited in the original studies and relevant review articles were also performed. All studies included in this metaanalysis were published in English. Results. In the end, 20 studies that met our inclusion criteria were included in our metaanalysis. Use of febuxostat was found not to be associated with an increased risk of all-cause mortality (RR 0.87, 95% CI 0.57-1.32, P = 0.51). Also, there was no association between febuxostat use and mortalities arising from CV diseases (CVD; RR 0.84, 95% CI 0.49-1.45, P = 0.53). The RR also revealed that febuxostat use was not associated with CVD events (RR 0.98, 95% CI 0.83-1.16, P = 0.83). Further, the likelihood of occurrence of CVD events was found not to be dependent on febuxostat dose (RR 1.04, 95% CI 0.84-1.30, P = 0.72). Conclusion. Febuxostat use is not associated with increased risks of all-cause mortality, death from CVD, or CVD events. Accordingly, it is a safe drug for the treatment of gout.