Colchicine Prophylaxis Reduces Cardiovascular Risk in Patients with Gout

Using data from the Clinical Practice Research Datalink Aurum, researchers found that colchicine prophylaxis at urate-lowering therapy initiation may lower cardiovascular event risk in patients with gout.

For their retrospective cohort study, Edoardo Cipolletta, MD and colleagues assessed whether gout flare prophylaxis with colchicine at the initiation of urate-lowering therapy was associated with a reduced risk of cardiovascular events. Among 99,800 patients with gout who started urate-lowering therapy, 16,028 received colchicine prophylaxis, while 83,772 did not. Over 180 days of follow-up, the risk of myocardial infarction or stroke was lower in the colchicine prophylaxis group (1.4%) compared with the no-prophylaxis group (1.8%), with an adjusted hazard ratio (HR) of 0.82 (95% CI, 0.69 to 0.94). The absolute risk reduction was –6.5 cardiovascular events per 1000 person-years, and the number necessary to treat was 154 to prevent one cardiovascular event.

Gout is a common inflammatory arthritis, with urate-lowering therapy effectively preventing flares when serum urate is maintained below 360 μmol/L. However, the initial reduction in serum urate can precipitate flares, necessitating prophylaxis, often with colchicine. Previous research has linked gout flares to increased cardiovascular risk, suggesting that flare prevention with colchicine may mitigate cardiovascular events. Despite these recommendations, only 10% to 20% of patients receive prophylaxis.

This study employed an emulated target trial framework with propensity score overlap weighting to minimize confounding. The researchers included patients newly diagnosed with gout between 1997 and 2021 and who had initiated urate-lowering therapy. Those prescribed colchicine prophylaxis for at least 21 days concurrently with urate-lowering therapy were compared with those not receiving prophylaxis. Cardiovascular events, including myocardial infarction and stroke, were identified using linked primary care, hospitalization, and mortality records. Secondary outcomes included first-ever cardiovascular events, fatal cardiovascular events, and individual myocardial infarction or stroke incidence.

Patients in the colchicine prophylaxis group had a mean duration of prophylaxis of 47.3 days (SD = 33.7), with a mean daily dose of 0.97 mg (SD = 0.16). The primary outcome occurred in 1.4% of patients receiving colchicine and 1.8% of those without prophylaxis, with a weighted incidence rate of 28.8 vs. 35.3 events per 1000 person-years. The adjusted HR for cardiovascular events was 0.82 (95% CI, 0.69 to 0.94) in the intention-to-treat analysis and 0.79 (95% CI, 0.58 to 0.99) in the per-protocol analysis, respectively. Colchicine use was also associated with a significant reduction in first-ever cardiovascular events (HR = 0.80; 95% CI, 0.62 to 0.97). An increased risk of diarrhea was the only significant adverse effect observed in the per-protocol analysis (HR = 1.32; 95% CI, 1.04 to 1.60).

Limitations include the observational design, which introduces potential residual confounding despite rigorous statistical adjustments. Additionally, the study spanned 25 years, raising concerns about changes in clinical practice over time.

“In patients with gout initiating urate-lowering therapy, gout flare prophylaxis with colchicine was associated with a lower rate of cardiovascular events for up to the next 180 days compared with no prophylaxis,” Cipolletta and colleagues concluded. “These findings provide an additional argument for using gout flare prophylaxis when starting urate-lowering therapy.”

Reference
Cipolletta E, Nakafero G, McCormick N, et al. Cardiovascular events in patients with gout initiating urate-lowering therapy with or without colchicine for flare prophylaxis: a retrospective new-user cohort study using linked primary care, hospitalisation, and mortality data. Lancet Rheumatol. Published online December 18, 2024. doi:10.1016/S2665-9913(24)00248-0