Abstract Body (Do not enter title and authors here): Introduction: Colchicine and NSAIDs are commonly used as flare prophylaxis during urate-lowering therapy (ULT) in gout, a chronic inflammatory condition linked to elevated cardiovascular risk. Oxidative stress and endothelial dysfunction may contribute to major adverse cardiovascular events (MACE). Although colchicine shows cardioprotective effects in non-gout populations and NSAIDs remain widely used despite risks, their effect on MACE in gout patients is unclear.
Research Question: Does flare prophylaxis with colchicine or NSAIDs alter the cardiovascular risk profile in patients with gout initiating ULT therapy?
Methods: This review followed PRISMA guidelines and was registered in PROSPERO (CRD420251017700). MEDLINE, EMBASE, and CENTRAL were searched through April 2025 for studies of gout patients initiating ULT with flare prophylaxis using colchicine, NSAIDs, or no prophylaxis. Studies involving non-gout crystal arthropathies, isolated hyperuricemia, or prophylaxis without ULT were excluded. The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, stroke, and coronary revascularization. Log-transformed hazard ratios (HRs) were pooled using a random-effects meta-analysis.
Results: Five studies from the UK, US, and Canada were included: three retrospective cohorts, one observational reanalysis of an RCT, and one target trial emulation. To avoid duplication with Cipolletta et al., only the CPRD GOLD subset was extracted from Roddy et al. Across four studies, 148,345 gout patients were included, with Singh et al. reporting 10,195 person-years of follow-up. Among them, 37,168 (25.1%) received colchicine and 19,461 (13.1%) received NSAIDs. Colchicine prophylaxis was not significantly associated with MACE risk compared to no prophylaxis [log(HR) = 0.005; 95% CI: -0.21 to 0.22, Figure 1]. NSAIDs also showed no significant difference [log(HR) = 0.19; 95% CI: -0.18 to 0.57, Figure 2]. Risk was similar between colchicine and NSAID groups [log(HR) = -0.02; 95% CI: -0.32 to 0.28, Figure 3].
Conclusion: Our meta-analysis found that flare prophylaxis with colchicine or NSAIDs did not reduce cardiovascular event risk in gout patients. These findings may contradict recent evidence of colchicine’s cardioprotective effects compared to NSAIDs. Further studies are needed to guide cardiovascular risk management in this high-risk population.