Applying Hypertension Clinical Trials to Real World Adults with CKD

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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.