Isla S Mackenzie 1, Ian Ford 2, George Nuki 3, Jesper Hallas 4, Christopher J Hawkey 5, John Webster 6, Stuart H Ralston 7, Matthew Walters 8, Michele Robertson 2, Raffaele De Caterina 9, Evelyn Findlay 1, Fernando Perez-Ruiz 10, John J V McMurray 8, Thomas M MacDonald 11, FAST Study Group
Main idea: Febuxostat is non-inferior to allopurinol therapy with respect to the primary cardiovascular endpoint, and its long-term use is not associated with an increased risk of death or serious adverse events compared with allopurinol.
Background: Febuxostat and allopurinol are urate-lowering therapies used to treat patients with gout. Following concerns about the cardiovascular safety of febuxostat, the European Medicines Agency recommended a post-licensing study assessing the cardiovascular safety of febuxostat compared with allopurinol.
Methods: We did a prospective, randomized, open-label, blinded-endpoint, non-inferiority trial of febuxostat versus allopurinol in patients with gout in the UK, Denmark, and Sweden. Eligible patients were 60 years or older, already receiving allopURinol, and had at least one additional cardiovascular risk factor. The primary outcome was a composite of hospitalization for non-fatal myocardial infarction or biomarker-positive acute coronary syndrome, stroke, or cardiovascular death. The study is registered with the EU Clinical Trials Register and ISRCTN and is now closed.
Findings: Allopurinol (n=3065) or febuxostat ( n=3063) were randomly allocated to receive treatment. By the study end date (Dec 31, 2019), 189 (6·2%) patients in the febUXostat group and 169 in the allopurinol group withdrew from all follow-up. For the incidence of the primary endpoint, on-treatment, febuxostat was non-inferior to allopurinol. The study was halted in 973 (32 4%) patients and 503 (16 5%) patients were discontinued from the study by the end of the study.