Cardiovascular outcomes of urate-lowering therapies in patients with gout or hyperuricemia: a network meta-analysis

Background: To evaluate the comparative cardiovascular safety of urate-lowering therapies (ULTs) in patients with gout or hyperuricemia. Research design and methods: Randomized controlled trials (RCTs) for ULTs with reported cardiovascular outcomes were included. Pairwise and network random-effect meta-analyses were performed to obtain the odds ratios (ORs) with 95% confidence intervals (CIs). The surface under the cumulative ranking curve (SUCRA) was employed to assess and rank the cardiovascular safety of ULTs. Results: A total of 3,663 literature were retrieved, of which 26 RCTs involving 25,329 patients were finally included. Pairwise and network meta-analyses showed that allopurinol demonstrated a significant reduction in arrhythmia compared with febuxostat (for pairwise meta-analysis, OR = 0.69, 95%CI 0.49 to 0.97; for network meta-analysis, OR = 0.71, 95%CI 0.51 to 0.99). Nevertheless, there was no statistically significant difference observed in other outcomes between different ULTs or between ULTs and placebo (p > 0.05). According to the SUCRA, febuxostat and pegloticase, had the highest probability of mitigating the occurrence of major adverse cardiovascular events (MACEs) and all-cause mortality respectively. Conclusions: Overall, ULTs showed relatively good cardiovascular safety in patients with gout or hyperuricemia. However, febuxostat has a higher risk of arrhythmia compared with allopurinol. Further studies are needed to confirm our findings.