Yokose Chio, McCormick Natalie, Lu Na, Jiang Bohang, Tan Kiara, Chigurupati Saiajay, Rai Sharan K, Challener Greg, Aviña-Zubieta J Antonio, Cipolletta Edoardo, Abhishek Abhishek, Gaffo Angelo, Januzzi James L, Zhang Yuqing, Choi Hyon K
Massachusetts General Hospital and Harvard Medical School, Boston.
Massachusetts General Hospital and Harvard Medical School, Boston, and Arthritis Research Canada, Vancouver, British Columbia, Canada.
Arthritis Rheumatol. 2025 May 26. doi: 10.1002/art.43259.
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.
在痛风患者中，尽管针对这一特定人群的安全性数据稀缺，但非甾体抗炎药（NSAIDs）仍被广泛使用。因此，我们对开始使用别嘌醇的痛风患者中，NSAIDs与秋水仙碱的心血管安全性进行了量化比较。
我们采用目标试验模拟框架，进行了一项序贯、倾向评分匹配的新用户比较有效性研究，以比较开始使用别嘌醇并被处方NSAIDs或秋水仙碱用于预防痛风发作的痛风患者发生主要不良心血管事件（MACE；心肌梗死[MI]、中风或心血管死亡的复合事件）的风险。敏感性分析采用治疗权重的逆概率（IPTW）。其次，我们研究了使用秋水仙碱或NSAIDs与不进行预防相比发生MACE的风险。
在18120名开始使用别嘌醇并使用NSAIDs或秋水仙碱的倾向评分匹配的痛风成年人中（83.5%为男性，平均年龄60.9岁），NSAIDs使用者发生MACE和心血管死亡的发生率高于秋水仙碱使用者，每1000人年的率差分别为38.8（95%置信区间[CI]15.4 - 62.2）和10.9（95%CI 0.7 - 21.1），危险比（HRs）分别为1.56（95%CI 1.11 - 2.17）和2.50（95%CI 1.14 - 5.26）。应用IPTW时结果相似。与不进行预防相比，使用NSAIDs与发生MACE和MI的风险更高相关，HRs分别为1.50（95%CI 1.17 - 1.91）和1.93（95%CI 1.35 - 2.75）。
在这些对开始使用别嘌醇的痛风患者的目标试验模拟中，NSAIDs预防与比秋水仙碱或不进行预防更高的MACE风险相关，提示应避免使用NSAIDs预防痛风发作。
