Real-world Evidence to Inform Decisions for Hypertension Treatment Escalation

真实世界证据为高血压治疗升级决策提供信息

• 批准号: 10718670
• 负责人: Yuan Lu
• 金额: $ 66.09万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-10 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10718670
• 关键词: Acute Kidney Failure; Address; Adult; Adverse event; Age; American; American Heart Association; Angioneurotic Edema; Antihypertensive Agents; Benefits and Risks; Calibration; Cardiology; Cardiovascular system; Characteristics; Clinical; Clinical Informatics; Clinical Practice Guideline; Clinical Research; Consumption; Data; Data Set; Databases; Development; Disease; Drug Combinations; Effectiveness; Electronic Health Record; Ethnic Origin; Future; Gastrointestinal Hemorrhage; Goals; Guidelines; Health; Healthcare; Heart failure; Heterogeneity; Hospitalization; Hypertension; Level of Evidence; Methods; Modeling; Morbidity - disease rate; Myocardial Infarction; National Heart, Lung, and Blood Institute; Observation in research; Observational Study; Outcome; Patients; Pattern; Persons; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacotherapy; Public Health; Publication Bias; Race; Randomized, Controlled Trials; Recommendation; Reproducibility; Research; Research Design; Research Methodology; Risk; Safety; Specific qualifier value; Stroke; Testing; Time; Translating; United States Department of Veterans Affairs; Variant; Work; active comparator; blood pressure control; clinical practice; college; comorbidity; comparative; comparative effectiveness; comparative safety; compare effectiveness; design; effectiveness evaluation; evidence based guidelines; experimental study; head-to-head comparison; hyperkalemia; hypertension control; hypertension treatment; implementation research; implementation science; improved; innovation; mortality; multidisciplinary; patient subsets; prevent; randomized trial; sex; trial comparing

Project Summary Over 100 million US adults have hypertension, a leading cause of mortality and morbidity, and 70% of them cannot achieve adequate blood pressure control with monotherapy alone. Although recent clinical practice guidelines suggest initiating therapy with two drugs, more than 50% of people currently treated for hypertension start with a single medication. For these patients, clinical guidelines propose adding a second antihypertensive drug for treatment escalation. The absence of head-to-head comparison in randomized controlled trials (RCTs) has limited the ability of clinical guidelines to provide evidence-based recommendations about which drug to add next for which patients. Our long-term goal is to produce real-world evidence to inform decisions about RCTs for hypertension treatment escalation and to provide the highest quality non-randomized evidence to support guideline recommendations. The overall objective in this application is to determine the comparative effectiveness and safety of the second antihypertensive agents added to monotherapy in patients with hypertension. The central hypothesis is that there is heterogeneity in the effectiveness and safety of the second antihypertensive agents, and the optimal choice depends on patient characteristics and the initial therapy. Our preliminary data demonstrate a large variation in the choice of the second agents added to monotherapy, providing ample opportunity to leverage practice variation to test our hypothesis. We will first determine the comparative effectiveness of the second antihypertensive agents added to monotherapy on major cardiovascular outcomes, such as myocardial infarction, stroke, and hospitalization for heart failure (Aim 1). We will then determine the comparative risk of the second antihypertensive agents on potential drug-related adverse events, such as acute renal failure, angioedema, gastrointestinal bleeding, and hyperkalemia (Aim 2). Finally, we will assess heterogeneity in effectiveness and safety among key patient subgroups defined by age, sex, race, and comorbidity (Aim 3). We have assembled experts in observational methods for causal inference, pharmacoepidemiology, clinical informatics, hypertension management, and implementation science, and will use real-world data from over 100 million US adults in five electronic health record (EHR) databases (i.e., Optum, Department of Veterans Affairs, Columbia, Yale, and Sentara Healthcare EHR databases). We will employ state- of-the-art observational research methods, including an active comparator new-user design, large-scale propensity score modeling, negative control outcome experiments, and empirical calibration, to emulate RCTs and to compare drug combinations. The proposed research is innovative because it will be the first study that applies massive real-world datasets and state-of-the-art observational research methods to comprehensively investigate the effectiveness and safety of the second antihypertensive agents added to monotherapy. The proposed research is significant because it provides critical evidence to inform decisions about RCTs for hypertension treatment escalation and to support guideline recommendations.

项目摘要 超过1亿美国成年人患有高血压，死亡率和发病率的主要原因，其中70％ 仅通过单一疗法就无法实现足够的血压控制。虽然最近的临床实践 指南建议使用两种药物开始治疗，超过50％目前接受高血压治疗的人 从一种药物开始。对于这些患者，临床指南建议添加第二种抗高血压 用于治疗升级的药物。在随机对照试验（RCT）中没有头对头比较 限制了临床准则提供有关添加哪种药物的循证建议的能力 下一个患者。我们的长期目标是提供现实世界的证据，以告知有关RCT的决定 高血压治疗升级并提供最高质量的非随机证据以支持 指南建议。本应用程序的总体目的是确定比较 第二种抗高血压剂的有效性和安全性在单一疗法中添加到单一疗法中 高血压。中心假设是第二个的有效性和安全性异质 降压药，最佳选择取决于患者特征和初始疗法。我们的 初步数据表明，在单一疗法中添加的第二代理的选择有很大差异， 提供足够的机会来利用实践变化来检验我们的假设。我们将首先确定 在主要心血管上添加到单一疗法中的第二种降压药的比较有效性 结局，例如心肌梗塞，中风和心力衰竭住院治疗（AIM 1）。然后我们会 确定第二种降压药对潜在药物相关不良事件的比较风险， 例如急性肾衰竭，血管性水肿，胃肠道出血和高钾血症（AIM 2）。最后，我们会的 评估由年龄，性别，种族和种族定义的关键患者亚组的有效性和安全性的异质性 合并症（目标3）。我们已经组装了因果推断观察方法的专家， 药物电子学，临床信息学，高血压管理和实施科学，并将 在五个电子健康记录（EHR）数据库中使用超过1亿美国成年人的现实世界数据（即optum， 哥伦比亚，耶鲁大学退伍军人事务部和Sentara Healthcare EHR数据库）。我们将雇用国家 - 现象研究方法，包括主动比较器新用户设计，大规模设计 倾向评分建模，负面对照结果实验和经验校准，以模仿RCT 并比较药物组合。拟议的研究具有创新性，因为这将是第一个研究 应用大量的现实数据集和最先进的观察研究方法来全面 研究添加到单一疗法中的第二种降压药的有效性和安全性。这 拟议的研究很重要，因为它提供了关键的证据，可以为RCT的决策提供信息 高血压治疗升级并支持指南建议。