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：
8451563
负责人：
David E Lanfear
金额：
$ 62.23万
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/8451563
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）是每年超过500,000例案例的巨大公共卫生问题，非裔美国人的个人承担不成比例的负担，包括与白人相比，较高的患病率和死亡率。 β肾上腺素能拮抗剂（Beta-Blockers，BB）是现代HF护理的基础，但他们在非裔美国人中的有效性尚不清楚。 HF中BB的关键临床试验对评估非裔美国人患者的能力严重不足，许多专家建议与白人患者相比，非裔美国人患者有差异性BB受益。这个问题需要其他数据和清晰度，因为改善了这种差异的理解和消除是国家研究的重点（Healthy People 2010）。多种因素可能导致BB效应的种族差异，例如遗传因素，药物依从性和合并症。所有这些因素必须详细表征，以评估哪些因素对此有助于这一因素。现有的药物遗传学研究表明，特定的变异可能解释了BB有效性的种族差异，但是这些研究尚未量化药物暴露或依从性，也没有包括足够数量的非裔美国人。为了回答这些问题，我们提出了1000名HF患者的种族多样，前瞻性的药物基因组登记册。我们的中心具有重要的优势来实现这一目标，包括大约一半的HF患者是非裔美国人，我们在使用药学索赔数据的量化依从性和药物暴露方面具有经验和基础设施。使用此队列，我们将评估种族和遗传因素对BB有效性的影响，这是通过临床事件（住院或死亡的时间）和健康状况来衡量的。最终，这些数据将阐明BB在非洲裔美国人中的好处，并有助于改善BB疗法对具有良好反应的可能性最高的人的靶向，同时避免可能反应不利的人。