QT prolonging medications and sudden cardiac death among individuals on hemodialysis

项目概要/摘要 接受维持性血液透析（HD）的个体具有极高的死亡率，主要由以下因素驱动： 心血管事件。HD人群的心源性猝死（SCD）发生率超过 人口增长20倍以上。SCD的风险因素，如结构性心脏病和传导 异常在终末期肾病患者中很常见，但传统的预防策略， 如抗心律失常药物和植入式心律转复器，不能降低HD患者的SCD风险 患者然而，药物引起的SCD可能是可以预防的，迄今为止，在HD中研究不足 患者透析患者经常被处方药物，这些药物具有不良的脱靶效应， 心室复极延迟，表现为心电图QT间期延长，以及 会引发致命的心律失常虽然超过50%的透析患者的处方药物， 延长QT间期（例如某些抗抑郁药、抗生素、止吐药）， 关于这些药物的心脏安全性的空白。事实上，它们的安全性取决于从以下数据中获得的数据： 健康志愿者，尚未在HD患者中进行明确评价。通过执行拟议的研究， 我们将全面了解与非处方药相关的基本安全性数据， HD患者的心脏QT延长药物。在目标1中，我们将确定 最常处方的QT延长潜力高于临床相关的非心脏药物 HD患者中QT延长潜力较低的对照药物。在目标2中，我们将确定 可能影响患者健康的可改变临床因素（例如透析液成分和合并处方药物） 旨在降低QT延长药物引起的SCD风险。在目标3中，我们将确定较高剂量的处方者 风险QT延长药物和相关的遭遇，应提示药物核对， 使用决策支持工具。然后，在目标4中，我们将为QT开发个性化的决策支持工具， 延长药物处方，整合许多合并症、HD治疗和药物- 相关风险因素。这项工作将产生决策支持工具，促进个性化的SCD风险 评估和更安全的QT延长药物处方，以降低HD患者的SCD风险。 此外，本项目产生的决策支持工具将作为未来实用试验的主题 测试工具实施对心血管结局的影响。

PROJECT SUMMARY/ ABSTRACT Individuals receiving maintenance hemodialysis (HD) have exceedingly high mortality, driven largely by cardiovascular events. The rate of sudden cardiac death (SCD) in the HD population exceeds that of the general population by more than 20-fold. Risk factors for SCD such as structural heart disease and conduction abnormalities are common among people with end-stage kidney disease, but traditional preventive strategies, such as antiarrhythmic medications and implantable cardioverter defibrillators, do not lower SCD risk in HD patients. However, medication-provoked SCD may be preventable, and, to-date, has been understudied in HD patients. Dialysis patients are often prescribed medications that have the undesirable, off-target effect of delayed ventricular repolarization, which manifests as QT-interval prolongation on an electrocardiogram, and can trigger fatal arrhythmias. Although more than 50% of dialysis patients are prescribed medications that can prolong the QT-interval (e.g. certain antidepressants, antibiotics, antiemetics), there are critical knowledge gaps about the cardiac safety of these medications. In fact, their safety profiles rest on data obtained from healthy volunteers and have not been explicitly evaluated in HD patients. By executing the proposed studies, we will provide a comprehensive understanding of the essential safety data relevant to the prescription of non- cardiac QT-prolonging medications to HD patients. In Aim 1, we will determine the relative SCD risk of the most commonly prescribed non-cardiac medications with higher QT-prolonging potential vs. clinically relevant comparator medications with lower QT-prolonging potential among HD patients. In Aim 2, we will identify modifiable clinical factors (e.g. dialysate composition and concurrent prescription medications) that may be targeted to mitigate SCD risk from QT-prolonging medications. In Aim 3, we will identify prescribers of higher risk QT-prolonging medications and associated encounters that should prompt medication reconciliation and decision support tool use. Then, in Aim 4, we will develop individualized decision support tools for QT- prolonging medication prescribing that integrate many comorbid conditions, HD treatment, and medication- related risk factors. This work will yield decision support tools that facilitate personalized SCD risk assessments and safer prescribing of QT-prolonging medications to reduce SCD risk among HD patients. Moreover, the decision support tools generated in this project will serve as the subject of future pragmatic trials testing the impact of tool implementation on cardiovascular outcomes.