MANCHESTER, England — Febuxostat (Uloric) did not appear to increase the risk for major adverse cardiovascular (CV) events (MACEs) when compared with no urate-lowering therapy (ULT) in people with gout, according to findings from a real-world, retrospective cohort study reported at the British Society for Rheumatology (BSR) 2025 Annual Meeting.
Using data primarily from the Clinical Practice Research Datalink (CPRD), UK researchers found that the composite primary outcome of MACEs — defined as myocardial infarction, ischemic stroke, heart failure hospitalization, unstable angina, revascularization, and cardiac mortality — occurred no more frequently among people who were treated with febuxostat than those who were not.
Although the rate of this primary outcome per 1000 person-years of treatment was initially higher in febuxostat users (66.01) than in allopurinol users (51.86) and in nonusers (40.13) using a univariate model, there was no statistically significant difference after multivariate adjustment. This included adjustment for patient age, sex, previous CV disease, ethnicity, hypercholesterolemia, hypertension, diabetes, chronic kidney disease, smoking status, social deprivation, body mass index, smoking status, co-prescriptions in the preceding 2 months, and the number of gout consultations and hospitalizations in the previous 12 months.
Indeed, the hazard ratio comparing febuxostat use with no ULT was 1.07 (95% CI, 0.99-1.16), reported study investigator Richard Partington, MBChB, MSc, PhD, a general practitioner in Morecambe, England, and National Institute for Health and Care Research Clinical Lecturer at Keele University, Staffordshire, England. In comparison, the hazard ratio comparing allopurinol use with no ULT was 1.19 (95% CI, 1.16-1.22).
CV Concerns Raised Then Allayed
Concern about the CV safety of ULT with febuxostat rose following the 2018 publication of results from the US Food and Drug Administration–mandated postmarketing trial called CARES, which was undertaken when studies in the drug development process for febuxostat suggested a modestly higher rate of CV events with febuxostat than with allopurinol. Although no difference between the drugs was seen in CARES for the primary endpoint of a composite of CV death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization, a secondary analysis suggested there was a higher rate of all-cause and CV mortality among febuxostat- vs allopurinol-treated patients.
In 2020, the results of the Febuxostat Versus Allopurinol Streamlined Trial (FAST) were p