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Investigating the comparative cardiac safety of selective serotonin reuptake inhibitors in the hemodialysis population

研究选择性血清素再摄取抑制剂在血液透析人群中的相对心脏安全性

基本信息

批准号：
9895589
负责人：
Magdalene Marie Assimon
金额：
$ 5.05万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9895589
关键词：
Investigating comparative cardiac safety selective

项目摘要

PROJECT SUMMARY/ABSTRACT Between 25% and 40% of hemodialysis patients have depression, a prevalence that exceeds that of the general population by 7- to 12-fold. This already high prevalence is primed to increase. In 2018, a new Centers for Medicare & Medicaid Services (CMS) clinical quality measure mandated that dialysis facilities report depression screening rates and treatment plans to CMS annually. This heightened focus will undoubtedly increase depression diagnosis and treatment, necessitating a better understanding of anti-depressant medication safety in the hemodialysis population. Selective serotonin reuptake inhibitors (SSRIs) warrant special consideration due to their role as a first-line depression treatment and differential propensity to cause lethal cardiovascular side effects. Even though 37% of U.S. hemodialysis patients are treated with an SSRI, little is known about the comparative cardiac safety of SSRIs this vulnerable population. An undesirable property of SSRIs is their ability to delay ventricular repolarization, an effect that manifests as QT interval prolongation on an electrocardiogram (ECG). Such a conduction abnormality creates an electrophysiologic environment that favors the development of rapidly fatal arrhythmias. ECG data indicate that all six SSRIs have QT prolonging capabilities at therapeutic doses. However, citalopram and escitalopram prolong the QT interval to the greatest extent, beyond the U.S. Food and Drug Administration’s threshold of regulatory concern. Thus, treatment with citalopram or escitalopram (vs. other SSRIs) may increase sudden cardiac death risk. Hemodialysis patients may be uniquely susceptible to citalopram- and escitalopram-triggered arrythmias due to their tremendous burden of structural heart disease, thrice-weekly exposure to electrolyte shifts during dialysis treatments, and extensive use of medications that can enhance the QT prolonging effects of SSRIs. Specifically, certain hemodialysis treatment conditions known to induce QT prolongation, such as exposure to wider (vs. narrower) electrolyte blood-to-dialysate gradients, likely amplify citalopram’s and escitalopram’s pro-arrhythmic effects. While clinical trials have demonstrated that SSRIs are efficacious anti-depressants in the hemodialysis population, their small sample sizes precluded adequate safety assessments. Leveraging administrative claims data from the U.S. Renal Data System linked with detailed electronic medical record data from a large U.S. dialysis provider, we will use modern epidemiologic study designs and analytic methods to: 1) investigate the comparative 1-year risk of sudden cardiac death between hemodialysis patients initiating SSRIs with higher (citalopram or escitalopram) vs. lower (fluoxetine, fluvoxamine, paroxetine or sertraline) QT prolonging potential; and 2) investigate the near-term risk of sudden cardiac death associated with concurrent exposure to SSRIs with higher (vs. lower) QT prolonging potential and wider (vs. narrower) electrolyte blood-to-dialysate gradients during hemodialysis treatments. This study will provide clinically-actionable knowledge about the comparative cardiac safety of SSRIs in the hemodialysis population, ultimately leading to more informed SSRI prescribing.

项目总结/摘要 25%至40%的血液透析患者患有抑郁症，其患病率超过了一般人群。人口增长7到12倍。这种已经很高的流行率有可能增加。在2018年，一个新的中心，医疗保险和医疗补助服务（CMS）临床质量措施要求透析设施报告抑郁症筛查率和治疗计划每年向CMS。这种高度重视无疑将增加抑郁症的诊断和治疗，需要更好地了解抗抑郁药物的安全性在血液透析人群中。选择性5-羟色胺再摄取抑制剂（SSRIs）值得特别考虑由于它们作为一线抑郁症治疗的作用和导致致命心血管疾病的不同倾向，副作用.尽管37%的美国血液透析患者接受SSRI治疗，但对SSRI的作用知之甚少。 SSRIs对这一脆弱人群的心脏安全性比较。SSRIs的一个不受欢迎的特性是它们的能力延迟心室复极，这一效应在心电图上表现为QT间期延长（ECG）。这种传导异常创造了一个有利于发展的电生理环境，快速致命的心律失常ECG数据表明，所有六种SSRI在治疗剂量下均具有QT延长能力。剂量然而，西酞普兰和艾司西酞普兰最大程度地延长QT间期，超出了美国食品和药物管理局的监管关注阈值。因此，西酞普兰或依他普仑治疗 (vs.其他SSRIs）可能会增加心脏性猝死风险。血液透析患者可能是唯一易受影响的西酞普兰和依他普仑由于结构性心脏病的巨大负担而引发的心律失常，透析治疗期间每周三次暴露于电解质变化，以及广泛使用可增强SSRIs的QT延长作用。具体而言，已知的某些血液透析治疗条件诱导QT间期延长，例如暴露于较宽（与较窄）电解质血液-透析液梯度，可能增强西酞普兰和依他普仑的促孕作用虽然临床试验已经证明， SSRIs在血液透析人群中是有效的抗抑郁药，其小样本量排除了充分的安全评估。利用来自美国肾脏数据系统的管理索赔数据，从美国一家大型透析提供商那里获得了详细的电子病历数据，我们将使用现代流行病学研究设计和分析方法：1）调查心源性猝死的比较1年风险在血液透析患者中，高剂量（西酞普兰或依他普仑）与低剂量（氟西汀，氟伏沙明、帕罗西汀或舍曲林）QT间期延长潜力;和2）研究近期突发性与同时暴露于具有较高（vs.较低）QT延长潜力的SSRI相关的心源性死亡，血液透析治疗期间较宽（与较窄）的电解质血液-透析液梯度。本研究将提供关于SSRI在血液透析中的比较心脏安全性的临床可操作知识人群，最终导致更明智的SSRI处方。