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Not so FAST! Febuxostat vs Allopurinol Showing Equal Safety –  Results of the FAST Trial in Europe

Not so FAST! Febuxostat vs Allopurinol Showing Equal Safety – Results of the FAST Trial in Europe

Optimal management of gout requires urate-lowering therapy; two commonly prescribed therapies for this are febuxostat and allopurinol. However, since 2018, the boxed warning placed on the prescribing information for febuxostat has led many practitioners to switch patients with risk factors for or preexisting cardiovascular disease (CVD) from febuxostat to allopurinol.

The CARES trial, published in the New England Journal of Medicine in 2018, showed an increased risk for cardiovascular (CV) and overall death when comparing febuxostat to allopurinol. Specifically, the trial showed a 34% increase in CV mortality and a 22% increase in overall mortality compared with allopurinol. Many reviewers noted dropout rates nearing 50% in the CARES trial, and thus were awaiting the FAST trial—which was a late breaking abstract (L08) at last year's annual American College of Rheumatology (ACR) conference in November. In contrast to the CARES study, the FAST study had excellent retention rates.

The FAST study compared allopurinol versus febuxostat in patients with gout and CVD; it recruited more than 6000 patients from the UK, Sweden, and Denmark. Like the CARES trial, the average time for follow-up was 4 years. The outcome showed no difference in CV death or overall mortality between the two groups. In fact, there was a numerically lower number of deaths in the febuxostat group than in the allopurinol group.

This was quite a different—and somewhat unexpected—outcome compared with the CARES trial, which clearly influenced the FDA in the United States. As a result of the FAST study, there will likely be a review of the boxed warning on febuxostat. Additionally, there may be changes to the ACR 2020 guidelines for the management of gout: Currently, the ACR 2020 guidelines strongly recommend allopurinol over all other drugs for initial urate-lowering therapy—even for patients with moderate to severe chronic kidney disease (stage ≥3). All in all, the FAST study should be good news, as we now have new information regarding febuxostat and can feel more confident regarding its overall safety in comparison to allopurinol.

References
  • FitzGerald JD, et al. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Care Res (Hoboken). 2020;72:744-760.
  • MacDonald T, et al. Long term cardiovascular safety of febuxostat and allopurinol in patients with chronic gout: The febuxostat versus allopurinol streamlined trial (on behalf of the FAST Investigators). Presented at: ACR Convergence 2020; November 2020; Virtual. Abstract L08.
  • White WB, et al. Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med. 2018;378:1200-1210.

Filed under: Cardiometabolic, Rheumatology

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