Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
ICES, Toronto, Ontario, Canada.
Diabetes Obes Metab. 2019 Jun;21(6):1322-1329. doi: 10.1111/dom.13656. Epub 2019 Mar 25.
To assess the association between allopurinol and mortality and cardiovascular outcomes in an allopurinol-treated diabetes cohort.
We conducted a population-based retrospective cohort study in Ontario, Canada. Eligible subjects were ≥ 66 years old with diabetes and a first prescription for allopurinol between 1 April, 2002 and 31 March, 2012 and were followed until 31 March, 2016. The primary outcome was a composite: all-cause mortality, non-fatal cardiovascular event (myocardial infarction, revascularization procedure, or stroke) or congestive heart failure (CHF). Secondary outcomes were components of the primary outcome and pneumonia as a negative tracer. Allopurinol was modelled as time-varying exposed versus unexposed, daily dose category and cumulative dose using sex-specific multivariable Cox proportional hazards models.
Over a median follow-up of 4.65 years (interquartile range 1.79-7.81), 16 266/23 103 males and 10 571/15 313 females experienced the primary outcome. Allopurinol was associated with a reduction in the primary outcome [adjusted hazard ratios (aHR) 0.77 (95% confidence interval 0.75-0.80) and 0.81 (0.78-0.84) for males and females, respectively], driven by marked reductions in all-cause mortality and modest reductions in cardiovascular events/CHF. There was no effect of cumulative allopurinol dose on any outcome, and allopurinol was also associated with reduced risk of pneumonia in males [aHR 0.88 (0.83, 0.93)].
Allopurinol was associated with reduced mortality and cardiovascular outcomes. However, lack of cumulative dose effect and a positive tracer outcome in males suggests residual bias. Future research assessing whether allopurinol prevents vascular complications in diabetes requires a clinical trial.
在接受别嘌醇治疗的糖尿病队列中，评估别嘌醇与死亡率和心血管结局的关系。
我们在加拿大安大略省进行了一项基于人群的回顾性队列研究。合格的受试者年龄≥66 岁，患有糖尿病，并且在 2002 年 4 月 1 日至 2012 年 3 月 31 日期间首次开处别嘌醇处方，随访至 2016 年 3 月 31 日。主要结局是复合结局：全因死亡率、非致死性心血管事件（心肌梗死、血运重建术或中风）或充血性心力衰竭（CHF）。次要结局是主要结局的组成部分和肺炎作为阴性示踪剂。使用基于性别的多变量 Cox 比例风险模型，将别嘌呤醇建模为随时间变化的暴露与未暴露、每日剂量类别和累积剂量。
在中位数为 4.65 年（四分位间距 1.79-7.81）的中位随访期间，16266/23103 名男性和 10571/15313 名女性经历了主要结局。别嘌醇与主要结局的降低相关[调整后的危险比（aHR）分别为 0.77（95%置信区间 0.75-0.80）和 0.81（0.78-0.84）]，这主要归因于全因死亡率的显著降低和心血管事件/CHF 的适度降低。累积别嘌醇剂量对任何结局均无影响，别嘌醇也与男性肺炎风险降低相关[aHR 0.88（0.83，0.93）]。
别嘌醇与死亡率和心血管结局降低相关。然而，由于男性中缺乏累积剂量效应和阳性示踪剂结局，表明存在残余偏倚。未来评估别嘌醇是否预防糖尿病血管并发症的研究需要临床试验。
