Op0151 Serum Urate Level and Cardiovascular Outcomes in Gout Patients With Administration of Febuxostat or Allopurinol: A Patient-Level Post-Hoc Analysis of the Cares Trial

Background: Researchers have investigated the potential role of uric acid in the development of cardiovascular (CV) disease. However, a recent large-scale randomized study showed that treatment with allopurinol 600 mg daily did not improve CV outcomes compared with usual care in patients aged 60 years or older with ischemic heart disease but no history of gout.¹ Still, it is unclear whether urate-lowering therapy (ULT) can reduce cardiovascular risk by lowering uric acid levels or whether ULT should be prescribed to improve CV outcomes in gout patients. Objectives: This study explored the relationship between serum uric acid (UA) levels and major adverse cardiovascular events (MACE) during the administration of febuxostat or allopurinol in gout patients. Methods: We re-analyzed the data from the Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout (CARES) trial. To investigate the association between controlled serum uric acid levels maintained by long-term ULT and CV disease in gout patients, we focused on those who continued the study medication for more than one year in the CARES trial. We investigated the serum uric acid level at the end of the first year of treatment as a potential risk factor for MACE following the first year of treatment, utilizing Cox regression analysis and Propensity Score matching. Results: In the overall cohort (n=4087), MACE after the first year of treatment occurred in 267 patients (6.5 %) during administration of the study drugs. Median duration of treatment was 3.1 (1.9-4.8) years. In Cox regression analysis, each incremental increase of per 1 mg/dL in serum uric acid level at the first year of treatment were associated with 10% increase in the hazard of MACE during administration of allopurinol or febuxostat (adjusted model 1, aHR, 1.10; 95% CI, 1.01-1.20, p-value = 0.0292). Patients with serum UA level ≥ 5 mg/dL at the first year of treatment had a significantly higher risk of MACE(adjusted model 2, adjusted HR 1.47, 95% CI 1.13 - 1.93, p-value 0.0048) compare to patients with a serum UA level < 5 mg/dL at the same time point. while an serum UA level ≥ 6 mg/dL at the first year of treatment was not statistically significant as a risk factor for MACE (adjusted model 3, adjusted HR 1.06, 95% CI 0.81 - 1.39, p-value = 0.6800) compare to patients with a serum UA level < 6 mg/dL at the same time point. Additionally, in PS matching, the HR was 1.49 (95% CI: 1.12 to 2.00, p-value = 0.0071) in patients with serum UA level ≥ 5 mg/dL at the first year of treatment compare to patients with a serum UA level < 5 mg/dL at the same time point. Conclusion: Among patients with gout and significant cardiovascular comorbidities, long-term control of low serum UA levels through febuxostat or allopurinol was associated with a reduced risk of MACE. REFERENCES: [1] Mackenzie IS, Hawkey CJ, Ford I, et al. Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial. Lancet 2022;400(10359):1195-1205. (In eng). DOI: 10.1016/s0140-6736(22)01657-9. Table 1. Cox proportional hazards regression analysis of factors associated with major adverse cardiovascular events during administration of febuxostat or allopurinol. Table 2. Incidence and risk of major adverse cardiovascular events during administration of febuxostat or allopurinol: Analysis using Cox proportional hazards regression and propensity-score matching. *All variables presented in Table 1 were adjusted Acknowledgements: This publication is based on research using data from data contributor, Takeda that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication. Disclosure of Interests: None declared.