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

基本信息

批准号：
7929469
负责人：
ALI AHMED
金额：
$ 40.27万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7929469
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

项目摘要

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500万估计的500万（预计为1000万）的一半在美国的心力衰竭（HF）患者患有舒张期HF或HF，左心室射血分数正常或接近正常的HF。这些患者大多数是老年人，HF是住院的主要原因（每年约100万）。舒张期HF的总体预后与收缩的HF或HF非常相似，而左心室射血分数则严重降低。然而，传统上，舒张期HF患者被排除在HF的主要随机临床试验（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影响：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，在三种强度匹配的有组织计划中，有组织的有组织的计划，以促进医院的患者的生命治疗（最佳心脏故障患者）的参与者（最佳患者）参与者（Imptim Imigizizizizizizize Imake Imake HART）。优化HF是一个大型（舒张压HF = 21,149），当代（2003-2004）和国家（涉及48个州的259位医院）数据库的大型HF（n = 48,612，N = 48,612，N = 21,149）。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）获取有关死亡率和住院的长期数据，并研究合格患者的神经瘤封锁和长期结局的关联。我们假设具有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会降低这些患者的死亡率和住院治疗。我们的假设基于观察结果，即左心室功能障碍的性质差异，发病机理（包括神经激活），临床表现以及收缩压和舒张性HF的结果非常相似，并且对这三种神经型调节剂的治疗却非常相似，已经证明了这三种神经型调节剂可降低Systolic HF中的死亡率和住院。具有确定的RCT研究神经激素阻滞在舒张期HF中的影响是理想的选择。但是，当RCT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得出最佳实践方法。倾向得分匹配最近已成为设计非RCT研究的工具，例如RCT，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，以指导舒张期HF的管理临床准则和实践，这些HF占所有HF患者的一半，并提高对这些患者的质量和护理结果。公共卫生相关性：几乎一半的心力衰竭患者患有舒张期心力衰竭，预后与收缩性心力衰竭相似。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在舒张性心力衰竭中的作用。拟议的研究将检查神经激素阻滞在倾向与舒张性心力衰竭的优化参与者匹配中的影响。