QT prolonging medications and sudden cardiac death among individuals on hemodialysis

项目摘要/摘要 接受维持性血液透析(HD)的人死亡率极高，主要原因是 心血管事件。HD人群中心脏性猝死(SCD)的发生率超过 总人口增加了20多倍。SCD的危险因素，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型心律转复除颤器，并不能降低HD患者发生SCD的风险 病人。然而，药物引起的SCD可能是可以预防的，到目前为止，HD还没有研究到这一点 病人。透析患者通常服用的处方药具有不良的、非靶向的效果 延迟的心室复极，在心电图上表现为QT间期延长，以及 会引发致命的心律失常。尽管超过50%的透析患者服用的处方药可以 延长QT间期(如某些抗抑郁药、抗生素、止吐剂)，有重要的知识 关于这些药物的心脏安全性的差距。事实上，他们的安全概况取决于从以下来源获得的数据 健康志愿者，尚未在HD患者中进行明确评估。通过执行拟议的研究， 我们将全面了解与非处方相关的基本安全数据 血液透析患者应用延长心脏QT间期药物。在目标1中，我们将确定以下项目的相对SCD风险 与临床相关的QT延长潜力较高的最常开出的非心脏药物 HD患者中QT延长潜伏期较低的对照药物。在目标2中，我们将确定 可修改的临床因素(例如透析液成分和同时服用处方药)可能是 旨在降低延长QT的药物引起的SCD风险。在目标3中，我们将确定Higher的处方者 风险QT-延长药物和相关遭遇，应促使药物调节和 决策支持工具的使用。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，包括多种并存疾病、HD治疗和药物治疗- 相关风险因素。这项工作将产生促进个性化SCD风险的决策支持工具 评估和更安全地开出延长QT的药物以降低HD患者的SCD风险。 此外，该项目中生成的决策支持工具将作为未来务实试验的主题 测试工具实施对心血管结果的影响。

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.