medwireNews: Among patients with gout, those who receive febuxostat treatment do not have a higher risk for cardiovascular (CV) events than those on allopurinol, according to the results of the FAST trial reported at the ACR Convergence 2020 virtual meeting and published simultaneously in The Lancet.
“In light of these findings, regulatory advice to avoid the use of febuxostat in patients with cardiovascular disease should be reconsidered and modified,” write Thomas MacDonald (University of Dundee, UK) and co-investigators.
They explain that the FAST trial was a post-licensing safety study recommended by the EMA “because of lingering concerns about the possibility of increased cardiovascular risk with febuxostat.”
Trial investigator Fernando Pérez-Ruiz: FAST suggests comparable CV safety of febuxostat vs allopurinol (4:14)
The study included 6128 gout patients (85% men) from the UK, Denmark, and Sweden who were aged at least 60 years (average 71 years), had one additional CV risk factor, and were already receiving allopurinol therapy, with a median allopurinol duration of 6 years. Participants were randomly assigned to receive oral febuxostat at a dose of 80–120 mg/day or to continue with allopurinol at the optimized dose established prior to study entry, typically 100–300 mg/day.
In the on-treatment analysis, 5.6% of 3063 participants treated with febuxostat experienced the primary composite endpoint of CV death, hospitalization for nonfatal myocardial infarction or biomarker-positive acute coronary syndrome, or nonfatal stroke during a median follow-up of 1467 days, compared with 7.9% of 3065 patients given allopurinol.
These findings translated into incidence rates of 1.72 and 2.05 per 100 person–years, respectively, indicating noninferiority of febuxostat versus allopurinol.
MacDonald and team also found that febuxostat was not associated with an increased risk for death or serious adverse events (AEs) compared with allopurinol in the intention-to-treat analysis. In all, 7.2% of patients in the febuxostat arm and 8.6% of those in the allopurinol group died, and the corresponding rates of serious AEs were 57.3% and 59.4%.
These results contrast with those of the CARES trial, reported previously by medwireNews, which was mandated by the US FDA and demonstrated significantly increased risks for all-cause and CV mortality with febuxostat versus allopurinol.
MacDonald and team say that “there were several differences between CARES and FAST.” For instance, all CARES participants had established CV disease at baseline, compared with just 33% of those in FAST, and CARES included patients with severe heart failure, whereas FAST excluded people with New York Heart Association functional class III or IV heart failure. They also note that 45.0% of CARES participants were lost to follow-up, compared with just 5.8% of those in FAST, suggesting “better ascertainment of events” in the current study.
Discussing the FAST results in a comment accompanying the publication in The Lancet, Thomas Bardin and Pascal Richette, both from Hôpital Lariboisière in Paris, France, say that the findings “appear to be robust and reassuring with regard to cardiovascular tolerance to febuxostat in the vast majority of white male patients with gout, although it does not allow firm conclusions to be drawn about patients with severe cardiovascular disease.”
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