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

Abstract

Objective To assess whether febuxostat use increases the risk of developing cardiovascular events, death from cardiac-cause and all-cause mortalities. Methods The relevant literature was searched in several databases including the MEDLINE (PubMed, 1 Jan. 1966–29 Feb. 2020), Web of science, EMBASE (1 Jan. 1974–29 Feb. 2020), ClinicalTrials.gov and Cochrane Central Register for Controlled Trials. Manual searches for references cited in the original studies and relevant review articles were also performed. All studies included in this metanalysis were published in English. Results In the end, 20 studies that met our inclusion criteria were included in this meta-analysis. 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 =0.507). Also, there was no association between febuxostat use and mortalities arising from cardiovascular diseases (CVD) (RR = 0.84, 95% CI 0.49–1.45, P=0.528). The RR also revealed that febuxostat use was not associated with CVD events (RR = 0.98, 95% CI 0.83–1.16, P =0.827). Furthermore, 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 =0.723). 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. Systematic review registration: PROSPERO CRD42019131872

Dr. Deng et al reply

“…We sincerely appreciate Dr. Kawada's comments in response to our metaanalysis. 1 We agree with most of these opinions and would like to clarify our views here.…”

“…4 Further, the doses of febuxostat intake were higher in the FAST trial. In our metaanalysis, 1 the pooled results indicated that the CV side effects of febuxostat were not significantly dose-dependent. Combined with a series of early clinical trial studies from Becker et al (ie, the CONFIRM trial 5 and FACT trial 6 ) as well as our metaanalysis, 1 febuxostat use was not associated with increased CV events and heart-related mortality.…”

`Risk of cardiovascular disease associated with febuxostat versus allopurinol use in patients with gout: a retrospective cohort study in Korea

“…In other words, this study observed the effects of febuxostat and allopurinol on the risk of cardiovascular disease under a condition in which both drugs were equally considered as first-line therapy in clinical settings. A recent meta-analysis study found that febuxostat use was not associated with an increased risk of cardiovascular events and death, all-cause mortalities [ 20 , 21 ]. In addition, febuxostat was found not to be associated with an increased risk of death or serious adverse events compared to allopurinol in a recent FAST (2020) study [ 22 ].…”

Febuxostat Use and Safety in Patients With Hyperuricemia

“…I read the paper by Deng et al, 1 in which the authors conducted a metaanalysis to evaluate whether febuxostat use increased the risk of developing cardiovascular (CV) events, cardiac death, and all-cause mortality. The adjusted relative risk (RR) of febuxostat use for all-cause mortality was 0.87 (95% CI 0.57-1.32).…”

“…I have 2 concerns about their study. 1 First, there are 2 clinical trials to compare the safety of allopurinol and febuxostat: the CARES trial and the FAST trial. 3,4 White et al concluded that "febuxostat was noninferior to allopurinol with respect to rates of adverse CV events.…”