Applying Hypertension Clinical Trials to Real World Adults with CKD

项目概要/摘要 高血压影响超过80%的慢性肾脏病（CKD）成人，其治疗是一种治疗方法。 CKD管理的基石。临床指南对血压目标的建议各不相同 在CKD中，反映了对收缩压干预试验（SPRINT）解释的不确定性 并将其外推至CKD成人患者，尤其是晚期CKD患者。虽然证据来自 随机试验具有很强的内部效度，它可能不能反映患者人群的风险受益特征， 在实践中接受治疗。我们的总体目标是评估以下方面的比较风险和收益： 在真实的CKD成人中强化与标准血压目标的比较。我们的第二个目标是 展示了新的分析方法的可行性和实用性，这些方法将因果效应从 随机试验对更广泛人群的影响。我们将通过利用电子健康来实现这些目标 记录数据来自两个大型医疗保健系统，包括1300万注册者-退伍军人健康 南加州的管理和凯撒永久。为了告知我们的真实世界估计，我们将 整合了来自4项不同高血压试验的20，000名参与者的个人水平数据。在目标1中，我们 在符合SPRINT条件的患者中，估计强化与标准血压目标的平均治疗效果 真实的成人CKD患者。在目标2中，我们将开发和验证用于个性化预测的模型， 强化血压治疗效果，并说明在真实的世界CKD人群中的应用。在Aim中 3、我们将效仿使用电子健康的血压药物强化的序贯临床试验 CKD患者的记录。我们的研究很重要，因为高血压治疗几乎影响所有成年人 CKD患者和关键证据缺口可能导致该高风险人群的管理不佳。是 创新，因为它将提供关于强化血压目标影响的新证据， 利用真实的世界数据支持临床决策的新分析方法。

PROJECT SUMMARY / ABSTRACT Hypertension affects more than 80% of adults with chronic kidney disease (CKD), and its treatment is a cornerstone of CKD management. Clinical guidelines vary in their recommendations for blood pressure targets in CKD, reflecting uncertainties in the interpretation of the Systolic Blood Pressure Intervention Trial (SPRINT) and its extrapolation to adults with CKD, particularly those with advanced CKD. Although evidence from randomized trials has strong internal validity, it may not reflect the risk benefit profile of patient populations that will receive treatment in practice. Our overarching goal is to evaluate the comparative risks and benefits of intensive versus standard blood pressure targets in real world adults with CKD. Our secondary goal is to demonstrate the feasibility and utility of novel analytical approaches that extend causal effects from randomized trial effects to broader populations. We will accomplish these goals by leveraging electronic health record data from two large health care systems encompassing 13 million enrollees - the Veterans Health Administration and Kaiser Permanente of Southern California. To inform our real-world estimates, we will integrate individual-level data from four diverse hypertension trials on 20,000 participants. In Aim 1, we will estimate average treatment effects of intensive versus standard blood pressure targets among SPRINT-eligible real world adults with CKD. In Aim 2, we will develop and validate models for individualized prediction of intensive blood pressure treatment effects, and illustrate the application in real world CKD populations. In Aim 3, we will emulate a sequential clinical trial of blood pressure medication intensification using electronic health records in persons with CKD. Our study is important because hypertension treatment affects nearly all adults with CKD and key evidence gaps may lead to suboptimal management in this high-risk population. It is innovative because it will provide new evidence about the implications of intensive blood pressure targets and new analytic approaches to support clinical decisions with real world data.