Association between allopurinol and cardiovascular outcomes and all-cause mortality in diabetes: A retrospective, population-based cohort study
Association between allopurinol and cardiovascular outcomes and all-cause mortality in diabetes: A retrospective, population-based cohort study
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DOI：
10.1111/dom.13656
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发表时间：
2019-06-01
影响因子：
5.8
通讯作者：
Hawker, Gillian A.
中科院分区：
文献类型：
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作者：
Weisman, Alanna;Tomlinson, George A.;Hawker, Gillian A.
旨在评估别嘌呤醇治疗的糖尿病队列中别嘌呤醇与死亡率与心血管结局之间的关联。材料和方法我们在加拿大安大略省进行了基于人群的回顾性队列研究。合格的受试者在2002年4月1日至2012年3月31日之间> = 66岁，患有糖尿病和别嘌呤醇的首次处方，然后一直持续到2016年3月31日。主要结果是一个复合材料：全因死亡率，非致命性死亡率心血管事件（心肌梗塞，血运重建程序或中风）或充血性心力衰竭（CHF）。次要结局是主要结局的组成部分，肺炎作为负示踪剂。别嘌醇被建模为随着时间变化的暴露与未暴露的，每日剂量类别和累积剂量，使用性别特定的多变量COX比例危害模型。结果中位随访4。65年（四分位间范围1.79-7.81），16 266/23 103男性和10 571/15 313女性经历了主要结果。别嘌呤醇与主要结果[调整危险比（AHR）0.77（95％置信区间0.75-0.80）和0.81（男性和女性分别为0.78-0.84）的降低有关，由全因降低。心血管事件/CHF的死亡率和适度降低。累积的同素醇剂量对任何结果都没有影响，别嘌呤醇也与雄性肺炎降低有关[AHR 0.88（0.83，0.93）]。结论别嘌呤醇与死亡率降低和心血管结局有关。但是，雄性缺乏累积剂量作用和阳性示踪结果表明残留偏见。未来的研究评估别嘌呤醇是否阻止糖尿病的血管并发症需要临床试验。
Aim To assess the association between allopurinol and mortality and cardiovascular outcomes in an allopurinol-treated diabetes cohort. Materials and Methods 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. Results 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)]. Conclusions 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.