Prognostic importance of early worsening renal function after initiation of angiotensin-converting enzyme inhibitor therapy in patients with cardiac dysfunction

• Published in: Circulation. Heart failure Vol. 4; no. 6; pp. 685 - 691
• Main Authors: Testani, Jeffrey M, Kimmel, Stephen E, Dries, Daniel L, Coca, Steven G
• Format: Journal Article
• Language: English
• Published: United States 01.11.2011
• Subjects: Aged; Angiotensin-Converting Enzyme Inhibitors - adverse effects; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Cardio-Renal Syndrome - diagnosis; Cardio-Renal Syndrome - etiology; Cardio-Renal Syndrome - mortality; Enalapril - adverse effects; Enalapril - pharmacology; Enalapril - therapeutic use; Female; Glomerular Filtration Rate - drug effects; Heart Failure - complications; Heart Failure - drug therapy; Heart Failure - physiopathology; Humans; Kidney - drug effects; Kidney - physiopathology; Male; Middle Aged; Prognosis; Retrospective Studies; Survival Rate; Ventricular Dysfunction, Left - complications; Ventricular Dysfunction, Left - drug therapy; Ventricular Dysfunction, Left - physiopathology
• ISSN: 1941-3289; 1941-3297
• DOI: 10.1161/CIRCHEARTFAILURE.111.963256

Worsening renal function (WRF) in the setting of heart failure has been associated with increased mortality. However, it is unclear if this decreased survival is a direct result of the reduction in glomerular filtration rate (GFR) or if the mechanism underlying the deterioration in GFR is driving prognosis. Given that WRF in the setting of angiotensin-converting enzyme inhibitor (ACE-I) initiation is likely mechanistically distinct from spontaneously occurring WRF, we investigated the relative early WRF-associated mortality rates in subjects randomized to ACE-I or placebo. Subjects in the Studies Of Left Ventricular Dysfunction (SOLVD) limited data set (n=6337) were studied. The interaction between early WRF (decrease in estimated GFR ≥20% at 14 days), randomization to enalapril, and mortality was the primary end point. In the overall population, early WRF was associated with increased mortality (adjusted hazard ratio [HR], 1.2; 95% CI, 1.0-1.4; P=0.037). When analysis was restricted to the placebo group, this association strengthened (adjusted HR, 1.4; 95% CI, 1.1-1.8; P=0.004). However, in the enalapril group, early WRF had no adverse prognostic significance (adjusted HR, 1.0; 95% CI, 0.8-1.3; P=1.0; P=0.09 for the interaction). In patients who continued to receive study drug despite early WRF, a survival advantage remained with enalapril therapy (adjusted HR, 0.66; 95% CI, 0.5-0.9; P=0.018). These data support the notion that the mechanism underlying WRF is important in determining its prognostic significance. Specifically, early WRF in the setting of ACE-I initiation appears to represent a benign event that is not associated with a loss of benefit from continued ACE-I therapy.