Febuxostat Safer Than Allopurinol for Asymptomatic Hyperuricemia

The researchers assessed the effects of febuxostat and allopurinol on mortality and adverse reactions in patients with hyperuricemia and gout.

Compared with allopurinol, febuxostat has improved safety outcomes and comparable rates of mortality and net clinical outcome for patients with hyperuricemia, according to study results published in Nutrition, Metabolism & Cardiovascular Diseases. However, for patients with gout, net clinical and safety outcomes were not significantly different with febuxostat or allopurinol.

The researchers retrieved data from PubMed and EMBASE for the randomized controlled trials of febuxostat and allopurinol from January 2005 to July 2018. They identified 13 trials with a total of 13,539 patients. The researchers recorded the number of deaths, serious adverse reactions, and adverse skin reactions for each study.

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The results indicated that compared with patients who received allopurinol, patients who received febuxostat were not associated with increased risk for cardiac-related mortality (odds ratio [OR], 0.72; 95%, CI, 0.24-2.13; P =.55) and all-cause mortality (OR, 0.78; 95% CI, 0.31-2.0; P =.60).

In addition, significantly fewer adverse skin reactions were seen in the febuxostat group compared with the allopurinol group (OR, 0.50; 95% CI, 0.30-0.85; P =.01). Febuxostat vs allopurinol 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 =.02).

The researchers did not find a significantly different net clinical outcome (incident gout and safety outcome) among patients who received febuxostat compared with those who received allopurinol (OR, 1.04; 95% CI; 0.76-1.42; P =.79).

Study limitations included the issue of whether adverse skin reactions were equivalent to cardiac mortality among xanthine oxidase inhibitors, the difference in mortality based on treatment length resulting from a large proportion of patient withdrawal from treatment in long-term studies, and the consideration of subgroups of studies with different doses that made it challenging to calculate the overall effect of pooled studies.

“Future [randomized controlled trials] might assess whether lower doses of febuxostat improve cardiac-related mortality or net clinical outcomes,” the researchers wrote.


Liu C-W, Chang W-C, Lee C-C, et al. The net clinical benefits of febuxostat versus allopurinol in patients with gout or asymptomatic hyperuricemia – a systematic review and meta-analysis [published online June 24, 2019]. Nutr Metab Cardiovasc Dis. doi:https://doi.org/10.1016/j.numecd.2019.06.016