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）：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性心力衰竭或左心室射血分数正常或接近正常的心力衰竭。这些患者大多数是老年人，心力衰竭是他们住院的主要原因（每年约 100 万人）。舒张期心力衰竭的总体预后与收缩期心力衰竭或左心室射血分数中度至严重降低的心力衰竭非常相似。然而，舒张性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，并且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，对启动救生治疗组织计划的三个倾向匹配人群的长期影响患有舒张性心力衰竭的住院心力衰竭患者 (OPTIMIZE-HF) 参与者。 OPTIMIZE-HF 是一个大型（N=48,612，舒张期心力衰竭 n=21,149）、当代（2003-2004 年）和全国性（涉及 48 个州的 259 家医院）数据库，记录了现实生活中住院的心力衰竭患者，这些患者经常被排除在外。大型随机对照试验。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) 获取死亡率和住院治疗的长期数据，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联。我们假设使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进行神经激素阻断将降低这些患者的死亡率和住院率。我们的假设基于以下观察：尽管左心室功能障碍的性质存在差异，但收缩期和舒张期心力衰竭的发病机制（包括神经激素激活）、临床表现和结果非常相似，并且使用这三种神经激素调节剂进行治疗已被证明可以减少收缩性心力衰竭的死亡率和住院率。最好有明确的随机对照试验来研究神经激素阻断对舒张性心力衰竭的影响。然而，当随机对照试验不道德或不切实际时，精心设计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（例如随机对照试验）的工具，其中研究人员在研究设计过程中对研究结果不知情。我们的长期目标是提供证据来指导舒张期心力衰竭（占所有心力衰竭患者的一半）治疗的临床指南和实践，并提高这些患者的护理质量和结果。公共卫生相关性：所有心力衰竭患者中近一半患有舒张性心力衰竭，其预后与收缩性心力衰竭相似。神经激素拮抗剂可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作用。拟议的研究将检查神经激素阻断对患有舒张性心力衰竭的倾向匹配 OPTIMIZE-HF 参与者的影响。