Antipsychotics Linked to MI Risk in Dementia Patients
抗精神病药物增加痴呆患者心肌梗死风险

March 29, 2012 — Antipsychotic medications used to treat behavioral symptoms in elderly patients with dementia are associated with an increased risk for myocardial infarction (MI), especially during the first month of use, new research suggests.

2012年3月29日，新的研究表明：被用于治疗老年痴呆患者的行为症状的抗精神病药物增大了患者心肌梗死（MI）的风险。特别是在使用这种药物的第一个月。

A retrospective cohort study of more than 20,000 patients older than 64 years who were treated with cholinesterase inhibitors (ChIs) showed that those who also started using antipsychotics had a significantly higher risk of developing incident MI within the next year than those who did not use antipsychotics.
一个研究对象为年龄大于64岁超过20,000名使用胆碱酯酶抑制剂（ChIs）治疗的病人回顾性队列研究表明，在第一年开始合用抗精神病药物的患者发生心肌梗死的风险显著高于那些没有使用抗精神病药物的患者。

However, the hazard risk ratios (RRs) were highest within the first 30 days after treatment initiation (RR, 2.19) and dropped continuously at each subsequent assessment point.

然而，在开始治疗的30天之内，危害风险率（RRS）达到最高（RR，2.19），之后的每个评估的时间点，RR值在不断下降。

"Antipsychotics are widely prescribed to elderly with dementia, despite the presence of safety warnings," co-investigator Yola Moride, PhD, professor in the Faculty of Pharmacy at the University of Montreal, Canada, and researcher at the University of Montreal Research Center, told Medscape Medical News.
Dr. Yola Moride
加拿大蒙特利尔大学药学系教授Yola Moride博士和蒙特利尔大学的研究中心研究员联合研究，“痴呆症的高龄患者被广泛的使用抗精神病药物，尽管存在安全警告。”Wedscape医学新闻报道。

"Given the ever-increasing prevalence of dementia, an increase in the risk of heart attack associated with the use of antipsychotics would therefore represent an important public health issue," said Dr. Moride.
Moride博士说：“由于痴呆症的发病率日益增长，抗精神病药物的使用将增加相关的心脏病发作的风险，这将成为一个重要的公共卫生问题。”

The investigators note that this is the first study to show this particular increased risk in this patient population. They add that it also "highlights the need for communicating such risk and for close monitoring of patients during the first weeks of treatment."

研究者还指出，针对此种病患群体增加了特殊风险，这为首次研究。他们补充说， “在病人在治疗的第一疗程中需要密切监测和加强交流。

The study was published online March 26 in the Archives of Internal Medicine.
这项研究在线发表于3月26日内科学文献

New Hypothesis
新假设
"Antipsychotics are known to be associated with an increase in the risk of stroke and the risk of death in the elderly population with dementia," reported Dr. Moride。
“抗精神病药物证明增加了痴呆症的高龄患者中风的风险和死亡的风险。”Moride博士报道。

"Given that stroke and MI are both cardiovascular thrombotic events, one might hypothesize that antipsychotics are also associated with heart attack, [but] to our knowledge, this hypothesis had not been investigated previously."
“由于中风和心肌梗死是血栓性心血管事件，人们可能会假设，抗精神病药物与心脏病发作相关，但据我们所知，这种假设在这之前并没有被研究。”

The investigators evaluated randomly selected data on 37,138 older patients with dementia who were treated with ChIs between January 2000 and December 2009. The information was reported in prescription claims databases for the Quebec province.

研究人员随机选取2000年1月到2009年12月期间服用ChIs的37138名患有痴呆症高龄病患的数据，并进行了评估。此信息在魁北克省的处方索赔数据库报道。

The ChIs used were donepezil hydrochloride, rivastigmine, or galantamine hydrobromide.

胆碱酯酶抑制剂（ChIs）包括盐酸多奈哌齐，卡巴拉汀或氢溴酸加兰他敏。

The participants were then divided into subcohorts made up of incident users of any antipsychotics (n = 10,969; 66% women) and a random sample of non-users (n = 10,969; 65.7% women).

研究对象分为两组：服用任一抗精神病药物的患者（N =10,969;66％的女性）和随机选取不使用抗精神病药物的患者（N=10,969;65.7％的女性）。

Of the treated group, 97.8% received atypical antipsychotics (64.5% took risperidone, 21.6% took quetiapine fumarate, 11.7% took olanzapine). Of the remaining 2.2% who received conventional antipsychotics, 1.9% took prochlorperazine maleate and 0.3% took chlorpromazine hydrochloride.

Alpha

治疗组中，97.8％患者使用非典型抗精神病药物（64.5％使用利培酮，21.6％使用富马酸喹硫平，11.7％使用奥氮平）。其余2.2％患者使用传统抗精神病药物，1.9％使用马来酸丙氯拉嗪，0.3％使用了盐酸氯丙嗪。

All patients were followed for up to 1 year after treatment initiation.
所有患者在开始治疗的第1年内接受随访。
Modest, Time-Limited Increase

适度的，时间增加。
Results showed that 1.3% of the participants who started treatment with antipsychotics had an incident MI within 1 year.
结果表明，1.3％服用精神病药物治疗的患者1年以内发生心肌梗塞。

The hazard RRs of MI were 2.19 (95% CI, 1.11 - 4.32; P =0.02) during the first 30 days after treatment initiation, 1.62 (95% CI, 0.99 - 2.65) within the first 60 days, 1.36 (95% CI, 0.89 - 2.08) within the first 90 days, and 1.15 (95% CI, 0.89 - 1.47) within the first 365 days.
心肌梗塞 的危害性RRs为2.19（95％置信区间CI，1.11 - 4.32，P= 0.02）在开始接受治疗的30天内，60天为1.62（95％CI，0.99 - 2.65），90天为1.36（95％CI，0.89 - 2.08），365天为1.15（95％CI，0.89 - 1.47）。

Other significant risk factors for MI for patients who took antipsychotics included having diabetes (P = .002) or being male and older than 84 years (P = .006).
服用抗精神病药物的患者其他的显著的风险因素是（P = 0.002），男性和年龄超过84岁（P = 0.006）。

The investigators also conducted a self-controlled case series study that assessed only the new users of antipsychotics who experienced incident cases of MI (n = 804) within the entire 9-year study period (2000 - 2009; median follow-up time, 47 months).

研究人员还进行了自身对照研究，评估用药发生MI的患者，（n =804）在9年的研究期间（2000年- 2009年，中间随访时间，47个月）。

The incidence rate ratios for these patients were 1.78 (95% CI, 1.26 - 2.52; P = 0.001) for the first 30-day period after start of treatment, 1.67 (95% CI, 1.09 - 2.56; P = .02) for the 31- to 60-day period, 1.37 (95% CI, 0.82 - 2.28) for the 61- to 90-day period, and 1.18 for the remaining exposure period.
这些患者的发病率分别为1.78（95％CI，1.26 - 2.52，P= 0.001），在开始接受治疗起初的30天，1.67（95％CI，1.09 - 2.56，P= .02）31 - 60天，1.37（95％CI，0.82 - 2.28），61 - 90天，剩余时间发病率为1.18。

"Antipsychotic use is associated with a modest and time-limited increase in the risk of MI," write the investigators. "Further investigations with larger sample sizes should be undertaken to identify high-risk subpopulations."
“使用抗精神病药物增加了发生适度的、时间限制的心肌梗死的风险，”研究者写到。“应采用更大量的样本患者进行研究，来鉴定发生心梗高风险的病患亚群。”

Dr. Moride added that these findings should be considered when weighing the benefits and risks of using antipsychotics.

Moride博士补充道，应考虑使用抗精神病药物的好处和风险，对其进行权衡。

"In addition, the risk is time dependent. Hence, it is important to follow patients closely during the first 2 months," she said.时间依赖性
“除此之外，此风险是随着时间变化的。因此密切跟踪起初治疗2个月的患者尤为重要。”她说。

Need for Clarification
需要澄清
"The increased risk for death associated with antipsychotic use has raised several important questions, and among them is the question of how exposure to these drugs leads to death," write Sudeep S. Gill, MD, and Dallas P. Seitz, MD, in an accompanying editorial.
“抗精神病药物的使用增加了死亡风险，会产生几个重要问题，包括这些药物如何导致死亡，Sudeep S..Gill医师和在P. Seitz医师在随后的文章中写出。

Both editorialists are from Queen's University in Kingston, Ontario, Canada. Dr. Gill is from the University's Department of Medicine and Dr. Seitz is from the Department of Psychiatry.

两位来自加拿大安大略省的金斯敦女王大学。吉尔博士是来自于大学医学系，Seitz博士是来自于精神病学系。

They note that although this study "adds valuable information," several limitations weaken its conclusion of a causal link between use of antipsychotics and MI.

他们表示，“虽然这项研究提供了有价值的信息，”仍然有一些限制削弱使用抗精神病药物和MI之间的因果关系的结论。

These include that there was no clear explanation to explain this effect, leading the editorialists to call for further research to clarify these mechanisms.
这些包括，没有明确的解释能够解释这种现象，需要进一步更深入的研究来阐明这些机理。

"Meanwhile, physicians should limit prescribing of antipsychotic drugs to patients with dementia and instead use other techniques when available, such as environmental and behavioral strategies, to keep these patients safe and engaged," they conclude.

“同时，对痴呆症患者而言，应该限制对精神病药物使用的处方，而使用其他可行技术来替代，例如环境和行为策略，使这些患者安全和参与，”他们得出的结论。