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

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，非裔美国人承担了不成比例的负担，包括与白色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HF治疗的基础，但其在非洲裔美国人中的有效性尚不清楚。BB在HF中的初步临床试验评估非洲裔美国人患者的效力不足，许多专家认为与白色患者相比，非洲裔美国人患者的BB获益不同。这个问题需要更多的数据和明确性，因为提高认识和消除这种差异是国家研究的优先事项（健康人2010）。多种因素可能导致BB效应的种族差异，如遗传因素、药物依从性和共病。所有这些因素都必须详细描述，以评估哪些因素对此有贡献。现有的药物遗传学研究表明，特定的变异可能解释BB有效性的种族差异，但这些研究没有量化药物暴露或依从性，也没有包括足够数量的非洲裔美国人。为了回答这些问题，我们提出了一个种族多样的，前瞻性的，药物基因组学注册的1000例HF患者。我们的中心在实现这一目标方面具有重要的优势，包括我们大约一半的HF患者是非洲裔美国人，并且我们在使用药房索赔数据量化依从性和药物暴露方面具有经验和基础设施。使用该队列，我们将评估种族和遗传因素对BB有效性的影响，通过临床事件（至住院或死亡的时间）和健康状况进行测量。最终，这些数据将阐明BB在非洲裔美国人中的益处，并有助于改善BB治疗对最有可能产生有利反应的患者的靶向，同时避免那些可能产生不利反应的患者。

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.