Neurohormonal Blockade and Outcomes in Diastolic Heart Failure

舒张性心力衰竭的神经激素阻断和结果

• 批准号: 7699418
• 负责人: ALI AHMED
• 金额: $ 51.28万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7699418
• 关键词: Abbreviations; Adrenergic beta-Antagonists; Aging; Alabama; Aldosterone Antagonists; American; American Heart Association; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor; Angiotensin-Converting Enzyme Inhibitors; Blinded; Cardiology; Cardiovascular system; Caring; Censuses; Chronic; Chronic Kidney Failure; Clinical; Clinical Practice Guideline; Communities; Confidence Intervals; Data; Data Analyses; Databases; Diastolic heart failure; Digitalis preparation; Elderly; Elderly woman; Enrollment; Equilibrium; Goals; Guidelines; Health; Heart; Heart failure; Hospitalization; Hospitals; Inpatients; Investigation; Left; Left Ventricular Dysfunction; Left Ventricular Ejection Fraction; Life; Link; Literature; Long-Term Effects; Medical Surveillance; Medicare; Methods; Morbidity - disease rate; Myocardial; National Heart, Lung, and Blood Institute; Nature; New York; Observational Study; Odds Ratio; Outcome; Outcome Study; Participant; Pathogenesis; Patient Care; Patients; Peer Review; Peptidyl-Dipeptidase A; Population; Practice Management; Prevalence; Principal Investigator; Provider; Public Health; Publications; Randomized Clinical Trials; Reader; Recommendation; Registries; Relative (related person); Renin-Angiotensin-Aldosterone System; Research; Research Design; Research Personnel; Risk Adjustment; Scoring Method; Source; Specific qualifier value; Systolic heart failure; United States; United States Centers for Medicare and Medicaid Services; United States National Institutes of Health; Universities; Vacuum; Ventricular; Vital Status; Work; base; beneficiary; cancer statistics; clinical practice; cohort; college; cost; design; drug efficacy; evidence base; experience; hazard; human old age (65+); improved; inhibitor/antagonist; male; mortality; outcome forecast; programs; public health relevance; tool

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.

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。这些患者中的大多数是老年人，HF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或伴有中度至重度左心室射血分数降低的HF非常相似。然而，舒张期HF患者传统上被排除在HF的主要随机临床试验（RCT）之外，并且几乎没有证据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舒张期心力衰竭住院患者救生治疗计划（OPTIMIZE-HF）参与者中的长期作用。OPTIMIZE-HF是一个大型（N= 48，612，舒张期HF n = 21，149）、当代（2003-2004）和国家（涉及来自48个州的259家医院）的真实住院HF患者数据库，这些患者通常被排除在大型RCT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，并研究神经激素阻滞与合格患者长期结局的相关性。我们假设，神经激素阻滞与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将减少这些患者的死亡率和住院治疗。我们的假设是基于以下观察结果：尽管左心室功能障碍的性质不同，但收缩期和舒张期HF的发病机制（包括神经激素激活）、临床表现和结局非常相似，并且这三种神经激素调节剂治疗已显示可降低收缩期HF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滞剂在舒张期HF中的作用。然而，当随机对照试验是不道德的或不切实际的，精心设计的观察性研究可以提供数据，以获得最佳实践方法。倾向评分匹配最近已成为设计非RCT研究（如RCT）的工具，在RCT中，研究者在研究设计期间对研究结果不知情。我们的长期目标是提供证据，指导舒张期HF（占所有HF患者的一半）的临床指南和实践，并提高这些患者的护理质量和结局。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性心力衰竭的结局，但没有证据表明其对舒张性心力衰竭的影响。拟定的研究将检查神经激素阻滞剂在舒张性心力衰竭倾向匹配的OPTIMIZE-HF受试者中的作用。