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

• 批准号: 8733261
• 负责人: David E Lanfear
• 金额: $ 21.32万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 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/8733261
• 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

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）：