NSAID Prophylaxis Linked to Higher CV Risk Than Colchicine in Gout Patients Starting Allopurinol

Reseachers who conducted a large comparative effectiveness study published in Arthritis & Rheumatology found that nonsteroidal anti-inflammatory drugs (NSAIDs) used for gout flare prophylaxis are associated with a significantly higher risk of major adverse cardiovascular events (MACE) compared to colchicine or no prophylaxis.

These findings support reconsideration of NSAID use in patients initiating urate-lowering therapy, particularly those at elevated cardiovascular risk, the authors stated.

The study analyzed data from 18,120 adults with gout initiating allopurinol, using a propensity score-matched, target trial emulation design. Patients receiving NSAIDs or colchicine for flare prevention were matched and followed for incident MACE, defined as a composite of myocardial infarction (MI), stroke, or cardiovascular death.

Among the matched cohort (83.5% male, mean age 60.9 years), the investigators reported, "the incidence of MACE and cardiovascular death were higher among NSAID users compared to colchicine users, with rate differences of 38.8 (95% CI, 15.4 to 62.2) and 10.9 (0.7 to 21.1) per 1000 person-years, respectively.” The hazard ratios were 1.56 (95% CI, 1.11–2.17) for MACE and 2.50 (95% CI, 1.14–5.26) for cardiovascular death when comparing NSAIDs to colchicine. These associations remained consistent in sensitivity analyses using inverse probability of treatment weighting.

When compared to no prophylaxis, NSAIDs also carried higher risks. “NSAID use was associated with a higher risk of MACE and MI with HRs 1.50 (1.17 to 1.91) and 1.93 (1.35 to 2.75), respectively,” the authors wrote. Colchicine, in contrast, was not associated with an elevated cardiovascular risk in either comparison group, reinforcing its safety profile in this context.

The investigators concluded, “NSAID prophylaxis was associated with a higher risk of MACE than colchicine or no prophylaxis, suggesting the avoidance of NSAID for gout flare prophylaxis.”

This evidence adds weight to the use of colchicine as the preferred agent for gout flare prevention during urate-lowering therapy initiation. Given the known cardiovascular burden among patients with gout, these findings may prompt changes in prophylaxis prescribing practices to prioritize long-term cardiovascular safety.

Reference
Yokose C, McCormick N, Lu N, et al. Comparative cardiovascular safety of nsaid versus colchicine use when initiating urate-lowering therapy among patients with gout: target trial emulations. Arthritis Rheumatol. Published online May 26, 2025. doi:10.1002/art.43259