Impact of Race and Genetic Factors on Beta-blocker Effectiveness in Heart Failure

种族和遗传因素对 β 受体阻滞剂治疗心力衰竭疗效的影响

基本信息

批准号：
8645702
负责人：
David E Lanfear
金额：
$ 64.16万
依托单位：
HENRY FORD HEALTH SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8645702
关键词：
Accounting Address Adherence Admixture Adrenergic beta-Antagonists Affect African African American Age Behavior Therapy Biological Factors Candidate Disease Gene Caring Cessation of life Chronic Clinical Clinical Trials Complex Computerized Medical Record Data Data Collection Data Sources Drug Exposure Effectiveness Electronics Environmental Risk Factor Etiology Event Failure Foundations Frequencies Genetic Genetic Determinism Genetic Variation Health Health Status Healthy People 2010 Heart Heart failure High Prevalence Hospitalization Individual Influentials Knowledge Laboratories Left Left Ventricular Dysfunction Link Maps Measures Myocardial Infarction Outcome Patient Recruitments Patients Pharmaceutical Preparations Pharmacogenetics Pharmacogenomics Pharmacotherapy Pharmacy facility Population Procedures Public Health Quality of life Race Registries Research Infrastructure Research Priority Resources Socioeconomic Status Solutions Surveys Time Validation Variant Work base cohort effectiveness measure electronic data experience gene interaction genetic variant genome wide association study improved knowledge base medication compliance mortality non-genetic novel novel strategies prospective racial difference receptor response sample collection social

项目摘要

DESCRIPTION (provided by applicant): Heart failure (HF) is an enormous public health problem with over 500,000 cases annually, and African American individuals share a disproportionate amount of this burden including a higher prevalence and mortality when compared with white individuals. Beta adrenergic antagonists (beta-blockers, BB) are the foundation of modern HF care, but their effectiveness in African Americans is not clear. Pivotal clinical trials of BB in HF were woefully underpowered to assess African American patients, and many experts have suggested a differential BB benefit in African American patients when compared with white patients. This issue requires additional data and clarity because improved understanding and elimination of such disparities is a national research priority (Healthy People 2010). Multiple factors may contribute to a racial disparity in BB effect such as genetic factors, medication adherence, and comorbid illnesses. All of these factors must be characterized in detail in order to evaluate which factor(s) contribute to this. Existing pharmacogenetic studies have suggested that specific variants may explain racial differences in BB effectiveness, but these studies have not quantified drug exposure or adherence and have not included a sufficient number of African Americans. In order to answer these questions, we propose a racially diverse, prospective, pharmacogenomic registry of 1000 HF patients. Our center has important advantages to achieve this including the fact that roughly half of our HF patients are African American, and we have experience and infrastructure in quantifying adherence and drug exposure using pharmacy claims data. Using this cohort we will assess the influence of race and genetic factors on BB effectiveness, measured by clinical events (time to hospitalization or death) and health status. Ultimately these data will clarify the benefit of BB in African Americans, and contribute to improved targeting of BB therapy to those with highest likelihood of favorable response while avoiding those likely to respond unfavorably.

描述（由申请人提供）：心力衰竭 (HF) 是一个巨大的公共卫生问题，每年有超过 500,000 例病例，非裔美国人承担着不成比例的负担，包括与白人相比更高的患病率和死亡率。 β 肾上腺素能拮抗剂（β 受体阻滞剂，BB）是现代心力衰竭治疗的基础，但其对非裔美国人的有效性尚不清楚。令人遗憾的是，BB 治疗心力衰竭的关键临床试验在评估非洲裔美国患者方面的效力严重不足，许多专家认为，与白人患者相比，BB 对非洲裔美国患者的益处存在差异。这个问题需要更多的数据和清晰度，因为提高对这种差异的理解和消除这种差异是国家研究的优先事项（Healthy People 2010）。多种因素可能导致 BB 效应存在种族差异，例如遗传因素、药物依从性和合并症。必须详细描述所有这些因素，以便评估哪些因素对此产生影响。现有的药物遗传学研究表明，特定变异可能解释 BB 有效性的种族差异，但这些研究并未量化药物暴露或依从性，也没有纳入足够数量的非裔美国人。为了回答这些问题，我们提议对 1000 名心力衰竭患者进行种族多样化、前瞻性药物基因组登记。我们中心拥有实现这一目标的重要优势，包括我们大约一半的心力衰竭患者是非裔美国人，并且我们拥有使用药房索赔数据量化依从性和药物暴露的经验和基础设施。利用这个队列，我们将通过临床事件（住院或死亡时间）和健康状况来衡量种族和遗传因素对 BB 有效性的影响。最终，这些数据将阐明 BB 对非裔美国人的益处，并有助于改善 BB 疗法针对那些最有可能产生有利反应的人，同时避免那些可能产生不利反应的人。