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50万例病例，非裔美国人承担了不成比例的这种负担，与白人相比，他们的患病率和死亡率更高。β-肾上腺素能拮抗剂(β-受体阻滞剂，BB)是现代心力衰竭护理的基础，但其在非裔美国人中的有效性尚不清楚。可悲的是，心力衰竭中BB的关键临床试验对非裔美国人患者的评估能力不足，许多专家建议，与白人患者相比，非裔美国人患者的BB益处不同。这个问题需要更多的数据和清晰度，因为改善对这种差异的理解和消除是国家研究的优先事项(健康人，2010年)。多种因素可能导致BB效应的种族差异，如遗传因素、服药依从性和并存疾病。所有这些因素都必须详细描述，才能评估哪个因素(S)对此做出了贡献。现有的药物遗传学研究表明，特定的变异可能解释了BB疗效的种族差异，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裔美国人。为了回答这些问题，我们建议对1000名心力衰竭患者进行种族多元化、前瞻性的药物基因组登记。我们的中心拥有实现这一目标的重要优势，包括我们大约一半的HF患者是非裔美国人，我们在使用药房索赔数据量化依从性和药物暴露方面拥有经验和基础设施。利用这个队列，我们将评估种族和遗传因素对BB疗效的影响，通过临床事件(住院或死亡时间)和健康状况来衡量。最终，这些数据将澄清BB在非裔美国人中的好处，并有助于改善BB治疗的针对性，使其针对那些反应良好的可能性最高的人，同时避免那些可能反应不利的人。

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.