OA01 Long-term cardiovascular safety of febuxostat compared with allopurinol or no urate-lowering treatment in people with gout: a cohort study in UK primary care using the Clinical Practice Research Datalink

Abstract

Background/Aims Febuxostat is recommended as first line urate-lowering therapy (ULT) for gout in the UK. However, concerns were raised regarding its cardiovascular (CV) safety. Current guidance advises caution when using it in people with CV disease, potentially denying people an effective treatment. Randomised trials have shown no difference in CV outcomes between febuxostat and allopurinol, but did not include a control group who did not receive ULT. This study compared CV safety in people with gout who received allopurinol, febuxostat or no ULT. Methods Retrospective cohort study, using data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) datasets. Adults aged ≥40 years with a SNOMED code for gout between 17/12/2008 and 31/03/2021 were included. We compared those prescribed (1)febuxostat, (2)allopurinol, or (3)no ULT. Individuals were considered at risk from index date until the earliest of first outcome event, death, end of treatment period or 31/03/21. Primary outcome was a composite of major CV events (myocardial infarction, ischaemic stroke, admission with heart failure, unstable angina, revascularisation and cardiac mortality), secondary outcomes assessed these individually. The incidence rate of each outcome in all three groups are presented with 95% confidence intervals (CI). The association between receiving either ULT, compared to those who received no prophylaxis, and first occurrence of each outcome was investigated using a multivariable Cox proportional hazards model, adjusting for sex, age, previous CVD, ethnicity, hypercholesterolaemia, social deprivation, BMI, smoking status, co-prescriptions in the two months prior to index date and number of gout consultations and hospitalisations in the 12 months prior to index date. Results 7,378 participants who were prescribed febuxostat and 97,940 who were prescribed allopurinol were compared with 200,387 who received no ULT. The groups were similar in age and sex distribution. Febuxostat users were more likely to have attended either primary or secondary care with gout in the 12 months prior to index date, had more co-prescriptions in the two months prior to index date, but were less likely to have received flare prophylaxis (33.3% vs 40.1%) compared with those who received allopurinol. The rate of primary outcome (per 1,000 person years, 95% CI) was higher in febuxostat users (66.01 (61.41, 70.97)) than those who received allopurinol (51.86 (50.85, 52.89)) or no ULT (40.13 (39.45, 40.81)). In the fully adjusted model, the composite primary outcome did not differ between febuxostat users and those not receiving ULT (hazard ratio (HR) 0.93 (95% CI 0.86-1.00)), whereas allopurinol was associated with slightly higher risk than no ULT (HR1.13(1.10-1.16)). Conclusion Febuxostat does not appear to increase the risk of major CV adverse events when used as ULT for patients with gout compared with not receiving ULT. These findings provide reassurance about using febuxostat in people with gout. Disclosure R. Partington: None. S. Muller: None. C.D. Mallen: None. M.A. Mamas: None. H. Forrester: None. E. Roddy: None.