Time-varying cardiovascular risk of febuxostat versus allopurinol in gout: a one-stage meta-analysis
- Journal
- Rheumatology (Oxford, England) (Q1)
- Published
- 21 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Qige Wei, Yang Shi, Rui Hu, Hui Wang, Yan Li, Li Luo, et al.
- PMID
- 42629330
- DOI
- 10.1093/rheumatology/keag457
Why clinicians should know about it
- Picked for Rheumatology (top studies of the week, 23 August 2026): Time‑varying CV risk of febuxostat vs allopurinol in gout patients
- Picked for Pharmacology (medical) (top studies of the week, 23 August 2026).
Abstract
OBJECTIVES: Whether febuxostat is associated with an increased cardiovascular risk compared to allopurinol in patients with gout remains controversial, with major randomized trials reporting conflicting results. This study aims to perform a comprehensive meta-analysis using reconstructed individual participant data (IPD) to evaluate the time-varying cardiovascular and mortality risk of febuxostat versus allopurinol in gout. METHODS: We conducted a one-stage individual participant data meta-analysis. PubMed, Embase, and Cochrane Library were searched up to November 2025 for randomized controlled trials and propensity score-matched observational studies reporting Kaplan-Meier curves for cardiovascular risk or all-cause mortality. Individual patient data were reconstructed from published curves. Time-varying hazard ratios (HRs) were estimated using a mixed-effects Cox model with treatment-by-time interaction across pre-specified intervals (0-12, 12-24, 24-48, >48 months). RESULTS: Four studies (n = 19,090) were included. Analysis revealed significant time-varying effects. For cardiovascular risk, HRs were 0.89 (95% CI 0.79 to 0.99) at 0-12 months, 0.58 (0.50 to 0.68) at 12-24 months, 0.86 (0.74 to 0.99) at 24-48 months, and 1.09 (0.81 to 1.46) after >48 months. For all-cause mortality, HRs were 0.70 (0.62 to 0.79), 0.39 (0.33 to 0.45), 0.75 (0.65 to 0.86), and 1.02 (0.77 to 1.34) across the same intervals, respectively. CONCLUSION: The cardiovascular and mortality risk of febuxostat relative to allopurinol is time-dependent, showing a significant early reduction that attenuates over time. These findings advocate for a time-aware approach to clinical management and monitoring.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.