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

描述(申请人提供)：大多数心力衰竭(HF)患者患有慢性肾脏疾病(CKD)。患有CKD的心力衰竭患者预后最差，但他们也最不可能接受血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂(ACEI/ARB)等救命药物的治疗。目前还没有针对HF-CKD患者的ACEI/ARB的随机对照试验(RCT)来指导临床实践，也不太可能在短期内进行。此外，临床医生通常认为ACE/AB相关的血清肌酐升高是肾脏损害的指标。如果没有强有力的证据证明ACEI/ARB对HF-CKD患者的生存益处，这种传统教学中根深蒂固的信念和做法不太可能改变。我们的特定假设是，ACEI/ARB可以减少CKD心力衰竭患者的死亡率和住院时间。我们的假设基于这样一个事实，即肾素-血管紧张素系统(RAS)的激活形成了HF和CKD的发病和进展的基础，而抑制RAS形成了ACEI/ARB的心脏和肾脏保护特性的基础。因此，我们假设同时患有心力衰竭和慢性肾脏病的患者将从这些药物中受益。阿拉巴马州心力衰竭计划(AHFP)是一个大型的(来自106家医院的8555名患者)、最近的(1998-2001)和丰富的数据集，具有200个明确的变量，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(女性占50%，非白人占20%)方面与现实生活中的心衰患者非常相似，因此可以对经常被排除在RCT之外的患者进行评估。此外，左心功能障碍研究(SOLVD)(N=2569；83家医院；平均年龄61岁，女性占20%，非白人占20%)的数据将被用来研究患有CKD的动态收缩期心衰患者的血管紧张素转换酶抑制剂的效果。本研究的具体目的是用倾向计分技术确定ACEI/ARB对CKD患者病死率和住院时间的影响，以及ARB(与ACEI相比)对HF-CKD患者死亡率和住院时间的影响。我们的长期目标是在严格设计和进行的非随机研究的基础上提供强有力的证据，这将挑战现有的在HF-CKD患者中不使用/未充分使用ACEI/ARB的临床实践，并改善HF护理的质量和结果。

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.