Objective To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia. Design Population based matched cohort study. Setting Linked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England. Population Adults (≥50 years) with a diagnosis of dementia between 1 January 1998 and 31 May 2018 (n=173 910, 63.0% women). Each new antipsychotic user (n=35 339, 62.5% women) was matched with up to 15 non-users using incidence density sampling. Main outcome measures The main outcomes were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury, stratified by periods of antipsychotic use, with absolute risks calculated using cumulative incidence in antipsychotic users versus matched comparators. An unrelated (negative control) outcome of appendicitis and cholecystitis combined was also investigated to detect potential unmeasured confounding. Results Compared with non-use, any antipsychotic use was associated with increased risks of all outcomes, except ventricular arrhythmia. Current use (90 days after a prescription) was associated with elevated risks of pneumonia (hazard ratio 2.19, 95% confidence interval (CI) 2.10 to 2.28), acute kidney injury (1.72, 1.61 to 1.84), venous thromboembolism (1.62, 1.46 to 1.80), stroke (1.61, 1.52 to 1.71), fracture (1.43, 1.35 to 1.52), myocardial infarction (1.28, 1.15 to 1.42), and heart failure (1.27, 1.18 to 1.37). No increased risks were observed for the negative control outcome (appendicitis and cholecystitis). In the 90 days after drug initiation, the cumulative incidence of pneumonia among antipsychotic users was 4.48% (4.26% to 4.71%) versus 1.49% (1.45% to 1.53%) in the matched cohort of non-users (difference 2.99%, 95% CI 2.77% to 3.22%). Conclusions Antipsychotic use compared with non-use in adults with dementia was associated with increased risks of stroke, venous thromboembolism, myocardial infarction, heart failure, fracture, pneumonia, and acute kidney injury, but not ventricular arrhythmia. The range of adverse outcomes was wider than previously highlighted in regulatory alerts, with the highest risks soon after initiation of treatment. Electronic health records are, by definition, considered sensitive data in the UK by the Data Protection Act and cannot be shared via public deposition because of information governance restriction in place to protect patient confidentiality. Access to Clinical Practice Research Datalink (CPRD) data is subject to protocol approval via CPRD’s research data governance process. For more information see . Linked secondary care data from Hospital Episodes Statistics, mortality data from the Office for National Statistics, and index of multiple deprivation data can also be requested from CPRD.

中文翻译：

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痴呆症患者使用抗精神病药物相关的多种不良后果：基于人群的匹配队列研究

目的 调查与痴呆症患者使用抗精神病药物相关的多种不良后果的风险。设计基于人群的匹配队列研究。设置来自英国临床实践研究数据链 (CPRD) 的关联初级保健、医院和死亡率数据。人口 1998年1月1日至2018年5月31日期间被诊断为痴呆症的成年人（≥50岁）（n=173 910，其中63.0%为女性）。使用发病密度抽样，将每位新的抗精神病药物使用者（n=35 339，其中 62.5% 为女性）与最多 15 名非使用者进行匹配。主要结局指标 主要结局指标为中风、静脉血栓栓塞、心肌梗塞、心力衰竭、室性心律失常、骨折、肺炎和急性肾损伤，按抗精神病药物使用周期分层，并使用抗精神病药物使用者与匹配对照者的累积发生率计算绝对风险。还对阑尾炎和胆囊炎联合的不相关（阴性对照）结果进行了研究，以发现潜在的未测量的混杂因素。结果与不使用相比，任何抗精神病药物的使用都与除室性心律失常之外的所有结果的风险增加相关。当前使用（处方后 90 天）与肺炎风险升高相关（风险比 2.19，95% 置信区间 (CI) 2.10 至 2.28）、急性肾损伤（1.72、1.61 至 1.84）、静脉血栓栓塞（1.62、1.46）至1.80）、中风（1.61、1.52至1.71）、骨折（1.43、1.35至1.52）、心肌梗塞（1.28、1.15至1.42）和心力衰竭（1.27、1.18至1.37）。阴性对照结果（阑尾炎和胆囊炎）没有观察到风险增加。在开始用药后 90 天内，抗精神病药物使用者中肺炎的累积发病率为 4.48%（4.26% 至 4.71%），而匹配的非使用者队列中肺炎的累积发病率为 1.49%（1.45% 至 1.53%）（差异为 2.99%、95 % CI 2.77% 至 3.22%）。结论 与不使用抗精神病药物的成年痴呆患者相比，使用抗精神病药物与中风、静脉血栓栓塞、心肌梗塞、心力衰竭、骨折、肺炎和急性肾损伤的风险增加相关，但与室性心律失常的风险无关。不良后果的范围比之前监管警报中强调的更广泛，在开始治疗后不久风险最高。根据定义，电子健康记录在英国被《数据保护法》视为敏感数据，并且由于为保护患者机密而实施的信息治理限制，无法通过公开宣誓共享。临床实践研究数据链 (CPRD) 数据的访问须通过 CPRD 的研究数据治理流程获得协议批准。欲了解更多信息，请参阅。还可以向 CPRD 索取来自医院事件统计的关联二级护理数据、来自国家统计办公室的死亡率数据以及多重剥夺数据索引。