Assessment of Cardiovascular Risk in Older Patients With Gout Initiating Febuxostat Versus Allopurinol: Population-Based Cohort Study.
Assessment of Cardiovascular Risk in Older Patients With Gout Initiating Febuxostat Versus Allopurinol: Population-Based Cohort Study.
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DOI：
10.1161/circulationaha.118.033992
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发表时间：
2018-09-11
期刊：
影响因子：
37.8
通讯作者：
Kim SC
中科院分区：
文献类型：
--
作者：
Zhang M;Solomon DH;Desai RJ;Kang EH;Liu J;Neogi T;Kim SC
高尿酸血症和痛风与心血管疾病（CVD）的风险增加有关。黄嘌呤氧化酶抑制剂（XOI）、别嘌呤醇和非布司他是痛风降尿酸治疗的主要药物，对痛风患者的心血管风险可能有不同的影响。使用美国医疗保险索赔数据（2008-2013年），我们在年龄≥65岁的痛风患者中进行了一项队列研究，比较了非布司他与别嘌呤醇的心血管安全性。主要结局是因心肌梗死（MI）或卒中住院的复合终点。次要结局为MI住院、卒中、冠状动脉血运重建、新发和复发性心力衰竭（HF）和全因死亡率的个体终点。我们使用倾向评分（PS）以1：3的比例与对照进行混杂匹配。我们估计了非布司他和别嘌呤醇启动者PS匹配队列中主要和次要结局的发生率（IR）和风险比（HR）。我们纳入了24，936例非布司他启动者与74，808例别嘌呤醇启动者PS匹配。中位年龄为76岁，52%为男性，12%在基线时患有心血管疾病。非布司他组和别嘌呤醇启动者组的主要结局发生率（IR）/100人-年分别为3.43和3.36。与别嘌呤醇组相比，非布司他组主要结局的HR为1.01（95%CI 0.94-1.08）。两组的次要结局风险（包括全因死亡率）相似，但非布司他治疗组HF加重风险适度降低（HR 0.94，95%CI 0.91-0.99）。与长期使用非布司他（>3年）相比，全因死亡率的HR为1.25（95%CI 0.56-2.80）。亚组和敏感性分析一致显示两组心血管风险相似。在99，744例老年痛风患者中，总体而言，与别嘌呤醇相比，非布司他组患者的MI、卒中、新发HF、冠状动脉血运重建或全因死亡率风险无差异。然而，与使用别嘌呤醇3年以上的患者相比，使用非布司他3年以上的患者的全因死亡风险似乎有增加的趋势，尽管无统计学显著性。非布司他治疗开始者的HF加重风险略低。
Hyperuricemia and gout are associated with increased risk of cardiovascular disease (CVD). Xanthine oxidase inhibitors (XOI), allopurinol and febuxostat, are the mainstay of urate lowering treatment for gout and may have different effects on cardiovascular risk in patients with gout. Using U.S. Medicare claims data (2008-2013), we conducted a cohort study for comparative cardiovascular safety of initiating febuxostat versus allopurinol among gout patients aged ≥65 years. The primary outcome was a composite endpoint of hospitalization for myocardial infarction (MI) or stroke. Secondary outcomes were individual endpoints of hospitalization for MI, stroke, coronary revascularization, new and recurrent heart failure (HF), and all-cause mortality. We used propensity score (PS) matching with a ratio of 1:3 to control for confounding. We estimated incidence rates (IR) and hazard ratios (HR) for primary and secondary outcomes in the PS-matched cohorts of febuxostat and allopurinol initiators. We included 24,936 febuxostat initiators PS-matched to 74,808 allopurinol initiators. The median age was 76 years, 52% were male, and 12% had cardiovascular disease at baseline. The incidence rate (IR) per 100 person-years for the primary outcome was 3.43 in febuxostat and 3.36 in allopurinol initiators. HR for the primary outcome was 1.01 (95%CI 0.94-1.08) in the febuxostat compared to allopurinol groups. Risk of secondary outcomes including all-cause mortality was similar in both groups, except for a modestly decreased risk of HF exacerbation (HR 0.94, 95%CI 0.91-0.99) in febuxostat initiators. The HR for all-cause mortality associated with long-term use of febuxostat (>3 years) was 1.25 (95%CI 0.56-2.80) versus allopurinol. Subgroup and sensitivity analyses consistently showed similar cardiovascular risk in both groups. Among a cohort of 99,744 older Medicare patients with gout, overall there was no difference in the risk of MI, stroke, new onset HF, coronary revascularization, or all-cause mortality between patients initiating febuxostat compared with allopurinol. However, there seemed to be a trend toward an increased, albeit not statistically significant, risk for all-cause mortality in patients who used febuxostat for over 3 years versus allopurinol for over 3 years. The risk of HF exacerbation was slightly lower in febuxostat initiators.