Neurohormonal Blockade and Outcomes in Diastolic Heart Failure

描述（由申请人提供）：美国估计有500万（预计到2040年将达到1000万）心力衰竭（HF）患者，其中近一半患有舒张期HF或左心室射血分数正常或接近正常的HF。这些患者大多是老年人，心衰是他们住院的主要原因（每年约100万）。舒张期HF的总体预后与收缩期HF或左室射血分数中度至重度降低的HF非常相似。然而，舒张性心衰患者一直被排除在主要的心衰随机临床试验（rct）之外，几乎没有证据可以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的长期效果：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，在三个倾向匹配的有组织的计划中启动挽救心力衰竭住院患者生命的治疗（优化-HF）参与者舒张期心力衰竭。OPTIMIZE-HF是一个大型（N=48,612，舒张期HF N= 21,149）、当代（2003-2004）和国家（涉及48个州的259家医院）的现实住院HF患者数据库，这些患者通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）获得死亡率和住院率的长期数据，并研究符合条件的患者神经激素阻断与长期预后的关系。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）、-受体阻滞剂或醛固酮拮抗剂阻断神经激素将降低这些患者的死亡率和住院率。尽管左心室功能障碍的性质不同，但收缩期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，使用这三种神经激素调节剂治疗已被证明可以降低收缩期心衰的死亡率和住院率。理想的情况是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，当随机对照试验不道德或不切实际时，设计良好的观察性研究可以提供数据，以获得最佳实践方法。倾向评分匹配最近成为一种设计非随机对照试验的工具，如随机对照试验，在研究设计过程中，研究者对研究结果是盲目的。我们的长期目标是为舒张性心衰（占所有心衰患者的一半）的临床指导和实践提供证据，并改善这些患者的护理质量和结果。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，其预后与收缩性心力衰竭相似。神经激素拮抗剂改善收缩期心力衰竭的预后，但没有证据表明它们对舒张期心力衰竭的影响。拟议的研究将检查神经激素阻断对倾向匹配的optime - hf患者舒张性心力衰竭的影响。

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.