Neurohormonal Blockade and Outcomes in Diastolic Heart Failure

描述(由申请人提供)：在美国估计的500万(预计到2040年将达到1000万)心力衰竭(HF)患者中，近一半的人患有舒张性心力衰竭或心力衰竭，其左心室射血分数正常或接近正常。这些患者大多是老年人，对他们来说，心力衰竭是住院的主要原因(每年约100万)。舒张性心力衰竭的总体预后与收缩心力衰竭或中度至重度左心室射血分数降低的心力衰竭非常相似。然而，舒张期心力衰竭患者传统上被排除在心力衰竭的主要随机临床试验(RCT)之外，几乎没有证据来指导这些患者的治疗。我们的近期目标是研究三种神经激素拮抗剂：血管紧张素转换酶抑制剂(或血管紧张素受体阻滞剂)、β受体阻滞剂和醛固酮拮抗剂在三个倾向匹配的人群中的长期效果。OPTIMIZE-HF是一个大型(N=48,612，n对于舒张期HF=21,149)、当代(2003-2004年)和国家(涉及48个州的259家医院)的真实住院HF患者的数据库，这些患者经常被排除在大型随机对照试验之外。我们将与研究数据援助中心(ResDAC)合作，从医疗保险和医疗补助服务中心(CMS)获得关于死亡率和住院时间的长期数据，并研究神经激素阻断与符合条件的患者的长期结果之间的关系。我们假设，用血管紧张素转换酶抑制剂(或血管紧张素受体阻滞剂)、β受体阻滞剂或醛固酮拮抗剂阻断神经激素将减少这些患者的死亡率和住院时间。我们的假设基于这样的观察：尽管左心功能不全的性质不同，但收缩和舒张期心衰的发病机制(包括神经激素激活)、临床表现和结局非常相似，这三种神经激素调节剂的治疗已被证明可以减少收缩心力衰竭的死亡率和住院时间。最好有明确的随机对照试验来研究神经激素阻断对舒张期心衰的影响。然而，当随机对照试验是不道德的或不切实际的时候，设计良好的观察性研究可以提供数据来得出最佳实践方法。倾向评分匹配最近已成为设计非随机对照试验等非随机对照试验的工具，在随机对照试验中，研究人员在研究设计期间对研究结果视而不见。我们的长期目标是提供证据，指导舒张性心力衰竭的临床指南和实践，并改善这些患者的护理质量和结果。舒张性心力衰竭占所有心力衰竭患者的一半。公共卫生相关性：近一半的心力衰竭患者患有舒张性心力衰竭，其预后与收缩期心力衰竭相似。神经激素拮抗剂改善了收缩性心力衰竭的预后，但没有证据表明它们对舒张性心力衰竭的影响。这项拟议的研究将检验神经激素阻断对患有舒张性心力衰竭的倾向匹配的OPTIME-HF参与者的影响。

DESCRIPTION (provided by applicant): Nearly half of the estimated 5 million (projected to be 10 million by 2040) heart failure (HF) patients in the United States have diastolic HF or HF with normal or near-normal left ventricular ejection fraction. Most of these patients are older adults, for whom HF is the leading (~1 million per year) cause for hospitalization. The overall prognosis of diastolic HF is very similar to systolic HF or HF with moderately to severely reduced left ventricular ejection fraction. Yet, diastolic HF patients have traditionally been excluded from major randomized clinical trials (RCTs) of HF and there is little evidence to guide therapy for these patients. Our immediate goal is to study the long-term effects of three neurohormonal antagonists: angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), beta-blockers and aldosterone antagonists, in three propensity-matched populations of Organized Program to Initiate Life-Saving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) participants with diastolic HF. The OPTIMIZE-HF is a large (N=48,612, n for diastolic HF=21,149), contemporary (2003-2004) and national (involving 259 hospital from 48 states) database of real-life hospitalized HF patients who have often been excluded from large RCTs. We will work with the Research Data Assistance Center (ResDAC) to obtain long-term data on mortality and hospitalization from the Center for Medicare and Medicaid Services (CMS) and study the associations of neurohormonal blockade and long-term outcome in eligible patients. We hypothesize that neurohormonal blockade with angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), beta-blockers or aldosterone antagonists will reduce mortality and hospitalization in these patients. We base our hypothesis on the observations that despite differences in nature of left ventricular dysfunction, the pathogenesis (including neurohormonal activation), clinical presentation, and outcomes in systolic and diastolic HF are very similar and therapy with these three neurohormonal modulators have been shown to reduce mortality and hospitalization in systolic HF. It would be ideal to have definitive RCTs to study the effect of neurohormonal blockade in diastolic HF. However, when RCTs are either unethical or impractical, well-designed observational studies can provide data to derive best practice methods. Propensity score matching has recently emerged as a tool to design non-RCT studies like RCTs in which investigators are blinded to study outcomes during study design. Our long-term goal is to provide evidence that will guide clinical guidelines and practice for the management of diastolic HF, who comprise half of all HF patients, and improve quality and outcomes of care for these patients. PUBLIC HEALTH RELEVANCE: Nearly half of all heart failure patients have diastolic heart failure, which have similar prognosis as in systolic heart failure. Neurohormonal antagonists improve outcomes in systolic heart failure but there is no evidence regarding their effect in diastolic heart failure. The proposed study will examine the effect of neurohormonal blockade in propensity matched OPTIMIZE-HF participants with diastolic heart failure.