Major Cardiovascular Events in Patients with Gout and Associated Cardiovascular Disease or Heart Failure and Chronic Kidney Disease Initiating a Xanthine Oxidase Inhibitor

BACKGROUND: Several observational studies and meta-analyses have suggested that treating hyperuricemia in patients with gout and moderate or severe chronic kidney disease (CKD) may improve renal and cardiovascular (CV) outcomes. OBJECTIVE: To evaluate the impact of initiating allopurinol or febuxostat treatment on major CV events in patients with gout, preexisting CV disease (CVD) or heart failure (HF), and stage 3 or 4 CKD in a real-world setting. METHODS: Patients with gout (aged > 18 years) who initiated allopurinol or febuxostat treatment between 2009 and 2013 after a diagnosis of stage 3 or 4 CKD and CVD-including coronary artery disease (CAD), cerebrovascular disease, and peripheral vascular disease (PVD)-or HF were selected from the MarketScan databases. The major CV events included CAD-specific, cerebrovascular disease-specific, and PVD-specific events. Cox proportional hazards modeling identified the predictors of major CV events in aggregate, and of CAD, cerebrovascular disease, and PVD events, individually. RESULTS: During follow-up, 2426 patients (370 receiving febuxostat and 2056 receiving allopurinol; 63% male; mean age, 73 years) had 162 major CV events (3.8% in those receiving febuxostat vs 7.2% in those receiving allopurinol; P = .015). The rates of major CV events per 1000 person-years were 51.8 (95% confidence interval [CI], 28-87) in patients initiating febuxostat and 99.3 (95% CI, 84-117) among those initiating allopurinol. Overall, 49.4% of patients had a CAD event, 32.5% had a PVD event, and 23.5% had a cerebrovascular disease-specific event. Febuxostat initiation was associated with a significantly lower risk for a major CV event versus patients who initiated allopurinol (hazard ratio, 0.52; P = .02), driven in large part by lower PVD-specific events (P = .026). CONCLUSION: Patients with moderate-to-severe CKD and CVD or HF who initiated febuxostat treatment had a significantly lower rate of major CV events than patients who initiated allopurinol.