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

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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.