Anti-gout Medications and Risk of Cardiovascular Disease: A Nested Case-Control Study

Introduction: Gout is the leading cause of inflammatory arthritis and is also correlated with multiple comorbidities, including cardiovascular disease (CVD), whose future risk can be lowered by urate-lowering therapy (ULT) in gout patients. It is, however, still not clear whether its effect is associated with the days of usage and the adherence rate of ULT. Methods: Data were collected from Taiwan's National Health Insurance Research Database. The study period was from 1999/1/1 to 2013/12/31. In addition, patients with newly diagnosed gout from 2000 to 2012 and usage of antigout preparations (allopurinol or benzbromarone) within half a year among age ≥20 years old were enrolled in the study. The outcome of interest is CVD. New diagnosis of CVD after half a year of diagnosis of gout was included in the CVD group. Moreover, conditional logistic regression was used to evaluate the odds ratio of CVD in relation to the days of usage and to the adherence rate of ULT after the adjustment for potentially confounding variables. Results: A total of 3,706 gout patients with and without CVD have been included in the final analysis after a 1:1 propensity score that matched for age, sex, comorbidities, aspirin, and statin. The days of usage of allopurinol was <180 days and benzbromarone, in its turn, presupposed a higher risk of CVD. The adherence rate of allopurinol and benzbromarone at ≥ 0.7 both have a lower CVD risk: allopurinol (adjusted OR: 0.66 95% CI: 0.46-0.96), benzbromarone (adjusted OR: 0.68 95% CI: 0.50-0.91). The subgroup analysis revealed an adherence rate of ≥0.7 of ULT with a lower CVD was only found to be present in males and at age <65. Furthermore, the correlations were more pronounced in the ischemic heart disease subgroup than in the cerebrovascular disease group. Conclusion: This study reveals that gout patients taking ULT (allopurinol and benzbromarone) with an adherence rate of ≥0.7 are at a lower risk of developing CVD, especially with a younger age (<65) and if they are male. On top of this, the benefit is more pronounced in ischemic heart disease. Despite further prospective trials needing to be warranted to confirm our findings, health care providers may, bearing these conclusions in mind, emphasize the importance of adherence to ULT in gout patients.