Heart failure, chronic kidney disease, and renin-angiotensin system inhibition

描述（由申请人提供）：大多数心力衰竭（HF）患者患有慢性肾脏疾病（CKD）。慢性肾脏病心衰患者的病情最差，但他们也最不可能接受挽救生命的药物，如血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂（ACEI/ARB）。目前还没有ACEI/ARB在HF-CKD患者中的随机对照试验（RCT）来指导临床实践，而且近期也不太可能进行。此外，临床医生通常将ACE/AB相关的血清肌酐升高视为肾损伤的指征。如果没有强有力的证据表明ACEI/ARB对HF-CKD患者的生存获益，这种根深蒂固的传统教学信念和实践不太可能改变。我们的假设是ACEI/ARB可以降低心衰伴CKD患者的死亡率和住院率。我们的假设是基于这样一个事实，即激活的肾素-血管紧张素系统（RAS）形成的基础上的发病机制和进展的HF和CKD，抑制其形成的基础上的心脏和肾脏保护特性的ACEI/ARB。因此，我们假设HF和CKD患者将从这些药物中获益。亚拉巴马HF项目（AHFP）是一个大型（来自106家医院的8555例患者）、最近（1998-2001）和丰富的数据集，包含约200个定义明确的变量，包括血清肌酐、射血分数和药物。AHFP队列在年龄（平均77岁）和多样性（>50%女性，> 20%非白人）方面与现实生活中的HF患者非常相似，允许对经常被排除在RCT之外的患者进行评估。此外，左心室功能障碍研究（SOLVD）（N=2569; 83家医院;平均年龄61岁，20%为女性，20%为非白人）数据将用于研究ACEI对CKD非卧床收缩期HF患者的影响。本研究的具体目的是确定ACEI/ARB对收缩期和舒张期心力衰竭伴CKD患者死亡率和住院率的影响，以及ARB（与ACEI相比）对HF-CKD患者死亡率和住院率的影响。我们的长期目标是根据严格设计和实施的非随机研究，提供强有力的证据，挑战现有的HF-CKD患者不使用/未充分使用ACEI/ARB的临床实践，并改善HF护理的质量和结局。

DESCRIPTION (provided by applicant): Most heart failure (HF) patients suffer from chronic kidney disease (CKD). HF patients with CKD have one of the poorest prognoses, yet they are also least likely to receive life-saving medications such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB). There have been no randomized controlled trials (RCT) of ACEI/ARB in HF-CKD patients to guide clinical practice, and none are likely to be conducted soon. Moreover, clinicians often perceive ACE/AB-associated rise in serum creatinine as an indication of renal damage. This belief and practice engrained in traditional teaching is unlikely to change without strong evidence of survival benefit of ACEI/ARB in HF-CKD patients. Our specific hypothesis is that ACEI/ARB would reduce mortality and hospitalization in HF patients with CKD. We base our hypothesis on the fact that activation of the renin-angiotensin system (RAS) forms the basis of the pathogenesis and progression of both HF and CKD, suppression of which forms the basis of cardio- and reno-protective properties of ACEI/ARB. Therefore, we postulate that patients with both HF and CKD will benefit from these drugs. Alabama HF Project (AHFP) is a large (8555 patients from 106 hospitals), recent (1998-2001), and rich dataset with -200 well-defined variables including serum creatinine, ejection fraction, and medications. The AHFP cohort closely resembles real-life HF patients in terms of age (mean 77 years) and diversity (>50% women, > 20% non-whites), allowing the assessment of patients often excluded from RCT. In addition, Studies of Left Ventricular Dysfunction (SOLVD) (N=2569; 83 hospitals; mean age 61 years, 20% women, 20% nonwhite) data will be use to study the effect of ACEI of ambulatory systolic HF patients with CKD. The specific aims of this study are to determine the effects of ACEI/ARB on mortality and hospitalization in systolic and diastolic HF patients with CKD, and the effect of ARB (versus ACEI) on mortality and hospitalization in HF-CKD patients using propensity score technique. Our long-term goal is to produce strong evidence, based on a rigorously designed and conducted non- randomized study, which will challenge existing clinical practice of nonuse/underuse of ACEI/ARB in HF- CKD patients, and improve quality and outcomes of HF care.