The net clinical benefits of febuxostat versus allopurinol in patients with gout or asymptomatic hyperuricemia – A systematic review and meta-analysis

Systemic reviews and meta-analyses suggest hyperuricemia is a cardiovascular risk factor. The effects of xanthine oxidase inhibitors on cardiac outcomes remain unclear. We assessed the effects of febuxostat and allopurinol on mortality and adverse reactions in adult patients with hyperuricemia. PubMed and EMBASE were searched to retrieve randomized controlled trials of febuxostat and allopurinol from January 2005 to July 2018. The meta-analysis consisted of 13 randomized controlled trials with a combined sample size of 13,539 patients. Febuxostat vs. allopurinol was not associated with an increased risk of cardiac-related mortality in the overall population (OR: 0.72, 95% CI: 0.24–2.13, P = 0.55). Regarding adverse skin reactions, the patients receiving febuxostat had significantly fewer adverse skin reactions than those receiving allopurinol treatment (OR: 0.50, 95% CI: 0.30–085, P = 0.01). Compared with allopurinol, febuxostat was associated with an improved safety outcome of cardiac-related mortality and adverse skin reactions (OR: 0.72, 95% CI: 0.55–0.96, P = 0.02). The net clinical outcome, composite of incident gout and the safety outcome, was not different significantly in the patients receiving febuxostat or allopurinol (OR: 1.04, 95% CI: 0.76–0.1.42, P = 0.79). In sensitivity analyses, a borderline significance was found in the patients randomized to febuxostat vs. allopurinol regarding cardiac-related mortality (OR: 1.29, 95% CI: 1.00–1.67, P = 0.05) after the CARES study was included. Febuxostat vs. allopurinol was associated with the improved safety outcome and have comparable mortality and net clinical outcome in patients with hyperuricemia. PROSPERO(CRD42018091657). The patients randomized to febuxostat vs. allopurinol was associated with the improved safety outcome. [Display omitted] •Thirteen randomized controlled trials with a combined sample size of 13,539 patients.•Randomization to the febuxostat vs. allopurinol had a comparable risk of cardiac-related mortality.•Febuxostat vs. allopurinol had a decreased risk of skin adverse reaction.•Febuxostat vs. allopurinol had an improved safety outcome.•Regarding net clinical benefits, febuxostat and allopurinol are comparable.