Comparative Cardiovascular Safety of Nonsteroidal Anti-Inflammatory Drug Versus Colchicine Use When Initiating Urate-Lowering Therapy Among Patients With Gout: Target Trial Emulations.

Abstract

Among patients with gout, nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used despite scarce safety data in this specific population. Therefore, we quantified the comparative cardiovascular safety of NSAIDs versus colchicine among patients with gout starting allopurinol. We conducted a sequential, propensity score-matched, new-user comparative effectiveness study using the target trial emulation framework to compare the risk of major adverse cardiovascular events (MACE; composite of myocardial infarction [MI], stroke, or cardiovascular death) among patients with gout started on allopurinol who were prescribed NSAIDs or colchicine for gout flare prophylaxis. A sensitivity analysis employed inverse probability of treatment weighting (IPTW). Secondarily, we examined the risk of MACE with colchicine or NSAIDs versus no prophylaxis. Among 18,120 propensity score-matched adults with gout starting allopurinol with NSAIDs or colchicine (83.5% male, mean age 60.9 years), the incidence of MACE and cardiovascular death were higher among NSAID users compared to colchicine users, with rate differences of 38.8 (95% confidence interval [CI] 15.4-62.2) and 10.9 (95% CI 0.7-21.1) per 1,000 person-years, respectively, and hazard ratios (HRs) of 1.56 (95% CI 1.11-2.17) and 2.50 (95% CI 1.14-5.26), respectively. Results were similar when IPTW was applied. Compared to no prophylaxis, NSAID use was associated with a higher risk of MACE and MI, with HRs of 1.50 (95% CI 1.17-1.91) and 1.93 (95% CI 1.35-2.75), respectively. In these target trial emulations of patients with gout starting allopurinol, NSAID prophylaxis was associated with a higher risk of MACE than colchicine or no prophylaxis, suggesting the avoidance of NSAID for gout flare prophylaxis.