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多潘立酮在帕金森病患者中的使用与全因死亡率增加相关:英国一项基于人群的队列研究。

Increased risk of all-cause mortality associated with domperidone use in Parkinson's patients: a population-based cohort study in the UK.

机构信息

Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.

Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

出版信息

Br J Clin Pharmacol. 2018 Nov;84(11):2551-2561. doi: 10.1111/bcp.13708. Epub 2018 Aug 9.

Abstract

AIMS

Domperidone is used to treat gastrointestinal symptoms in patients with Parkinson's disease (PD) and is linked to an increased risk of mortality. We sought to examine the risk of all-cause mortality associated with domperidone exposure in PD.

METHODS

We conducted a cohort study using data from the Clinical Practice Research Datalink database (1987-2011). The first recorded PD diagnosis defined index date. Time-dependent Cox proportional hazards models estimated hazard ratios (HRs) of all-cause mortality associated with domperidone use. PD patients were stratified by domperidone use (current/recent/past), with never used as the referent. Current domperidone users were stratified by daily dose, domperidone duration and other anti-Parkinson's medications. A secondary analysis compared PD patients to matched (1:1) non-PD patients.

RESULTS

A total of 5114 PD patients were identified. Current use of domperidone among PD patients was associated with a two-fold increase in all-cause mortality (HR  = 2.00, 95% confidence interval [CI]: 1.64-2.45), as compared to patients never exposed to domperidone. All-cause mortality risk was highest in those starting domperidone in the previous month [HR  = 2.97, 95% CI: 2.06-4.27]. When compared to matched non-PD patients, PD was associated with a 43% increased risk of all-cause mortality, yet this increased to a 2.4-fold increased risk among PD patients currently using domperidone.

CONCLUSION

Current use of domperidone was associated with a two-fold increased mortality risk in PD patients, as compared to PD patients that never used domperidone. The risk is highest in the first month of use and does not appear to be attributable to PD alone.

摘要

目的

多潘立酮用于治疗帕金森病(PD)患者的胃肠道症状,与死亡率增加有关。我们试图研究与 PD 患者多潘立酮暴露相关的全因死亡率风险。

方法

我们使用临床实践研究数据链接数据库(1987-2011 年)中的数据进行了队列研究。首次记录的 PD 诊断定义为索引日期。时间依赖性 Cox 比例风险模型估计了与多潘立酮使用相关的全因死亡率的风险比(HR)。根据多潘立酮使用情况(当前/近期/过去)对 PD 患者进行分层,从未使用过多潘立酮的患者作为参照。当前多潘立酮使用者根据每日剂量、多潘立酮持续时间和其他抗帕金森药物进行分层。一项次要分析将 PD 患者与匹配的(1:1)非 PD 患者进行比较。

结果

共确定了 5114 名 PD 患者。与从未暴露于多潘立酮的 PD 患者相比,当前 PD 患者使用多潘立酮与全因死亡率增加两倍相关(HR=2.00,95%置信区间[CI]:1.64-2.45)。与那些在过去一个月开始使用多潘立酮的患者相比,全因死亡率风险最高(HR=2.97,95%CI:2.06-4.27)。与匹配的非 PD 患者相比,PD 患者的全因死亡率风险增加了 43%,但在当前使用多潘立酮的 PD 患者中,这一风险增加了 2.4 倍。

结论

与从未使用过多潘立酮的 PD 患者相比,当前使用多潘立酮与 PD 患者的死亡率增加两倍相关。风险在使用的第一个月最高,似乎不是 PD 本身所致。

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