Febuxostat CV Safety — SCE Rheumatology MCQ

Correct answer: C — Febuxostat was non-inferior to allopurinol for the primary cardiovascular endpoint, with no associated increase in death or serious adverse events

FAST randomised 6,128 patients aged at least 60 years who had cardiovascular risk factors and were already receiving allopurinol. In the prespecified on-treatment analysis, febuxostat was non-inferior to dose-optimised allopurinol for the primary cardiovascular composite: adjusted HR 0.85 (95% CI 0.70–1.03), with the upper confidence limit below the 1.3 non-inferiority margin. It was not associated with increased death or serious adverse events. A point estimate below 1 does not establish superiority, and inclusion of 1 does not prevent demonstration of non-inferiority. FAST did not reproduce the CARES mortality signal, but its population excluded recent myocardial infarction or stroke, severe heart failure and severe renal impairment, so it does not establish safety in every gout population. UK guidance still recommends caution with febuxostat and allopurinol first-line in major cardiovascular disease.

Reference: MHRA. Febuxostat: updated advice for the treatment of patients with a history of major cardiovascular disease. Drug Safety Update, 2023. https://www.gov.uk/drug-safety-update/febuxostat-updated-advice-for-the-treatment-of-patients-with-a-history-of-major-cardiovascular-disease