Cardiovascular risk associated with allopurinol or benzbromarone treatment in patients with gout

Abstract

Background: In previous studies, cardiovascular (CV) risk was increased in patients with gout. The effects of uric acid-lowering therapy on CV risk in gout patients have been investigated in numerous studies; however, allopurinol and benzbromarone have rarely been compared.

Objectives: To compare CV risk based on allopurinol and benzbromarone treatment in Korean gout patients.

Design: A nationwide population-based retrospective cohort study.

Methods: We used South Korea database of the Health Insurance Review and Assessment (HIRA) service to identify gout patients ⩾18 years of age who newly started allopurinol or benzbromarone between 2009 and 2015. The primary outcome of the study was the occurrence of a composite CV endpoint, which included coronary revascularization, hospitalization due to myocardial infarction, ischemic stroke, and transient ischemic attack. Cox proportional hazard regression analysis and Kaplan-Meier curves were used for analysis.

Results: The study included 257,097 allopurinol initiators and 7868 benzbromarone initiators. Compared with allopurinol initiators, the adjusted hazard ratio (aHR) of the composite CV endpoint of benzbromarone initiators was 1.01 [95% confidence interval (CI): 0.83-1.21], which was not significantly different. The results did not change even when 1:3 propensity score matching was performed for baseline characteristics. In subgroup analysis of high-risk patients with CV disease, significant difference was not observed between allopurinol and benzbromarone initiators.

Conclusion: In this study, significant difference was not found in CV risk between allopurinol and benzbromarone initiators. In the high-CV-risk group, the incidence of CV events did not differ between allopurinol and benzbromarone initiators.

Keywords: allopurinol; benzbromarone; cardiovascular disease; gout; uric acid–lowering therapy.

Figure 1.

Flowchart of study population.

Figure 2.

Study design. CV, cardiovascular; HF, heart failure; MI, myocardial infarction; TIA, transient ischemic attack.

Figure 3.

Kaplan–Meier curves for cardiovascular (CV) outcome in allopurinol and benzbromarone initiators: (a) composite CV outcome; (b) hospitalization for myocardial infarction (MI); (c) hospitalization for stroke; (d) hospitalization for transient ischemic attack (TIA); (e) coronary revascularization; and (f) hospitalization for heart failure (HF).