CHICAGO—Febuxostat treatment for gout is associated with an increased risk of cardiovascular (CV) events only among patients with established CV disease, according to study findings presented during a late-breaking abstract poster session at the 2018 American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting in Chicago.

The study included an inception cohort of 256 patients with crystal-proven gout in whom xanthine oxidase inhibitor therapy was initiated and who had at least 6 months of follow-up. Of these, 213 and 43 patients were treated with allopurinol and febuxostat, respectively. Sixty-nine patients (27%) had established CV disease.

For the cohort as a whole, febuxostat was associated with a significant 3.9-fold increased risk of new CV events compared with allopurinol, after adjusting for multiple variables, Neus Quilis, MD, of Hospital Universitario del Vinalopó in Elche, Spain, and colleagues reported. Among patients with prior CV disease, febuxostat was associated with a significant 20.8-fold increased risk of new CV events compared with allopurinol.

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The investigators found no significant difference between allopurinol and febuxostat among patients without prior CV disease.

Over a median follow-up of 9.5 months, 22 new CV events occurred, including 13 cases of congestive heart failure, 5 cases of coronary heart disease, 2 cases of peripheral artery disease, and 2 strokes. Seven CV-related deaths resulted. Sixteen CV events occurred in patients with prior CV disease (23.2%) and 6 occurred in patients with no prior CV events (20.9%).

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In November 2017, FDA issued a warning about increased CV mortality risk associated with febuxostat compared with allopurinol. This past August, the agency announced it is reviewing results from the Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) trial, which was funded by Takeda Pharmaceuticals, which makes febuxostat. Results from this multicenter, randomized, double-blind non-inferiority trial were published last March in the New England Journal of Medicine. Investigators concluded that, in patients with gout and major CV coexisting conditions, febuxostat was non-inferior to allopurinol with respect to rates of CV events, but febuxostat was associated with greater all-cause and CV mortality compared with allopurinol.


1.    Quilis N, Ranieri L, Sanchez-Paya J, Andrés M. New cardiovascular events in patients with gout treated with xanthine-oxidase inhibitors: An inception cohort analysis. Presented at the 2018 ACR/ARHP Annual Meeting in Chicago, Oct. 19-24. Abstract L01.

White WB, Saag KG, Becker MA, et al. Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med. 2018;378:1200-1210.