title: Prognostic importance of early worsening renal function after initiation of angiotensin-converting enzyme inhibitor therapy in patients with cardiac dysfunction.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Cardiovascular Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA. jeffrey.testani@uphs.upenn.edu
authors: Jeffrey M
authors: JM
authors: Testani
authors: Stephen E
authors: SE
authors: Kimmel
authors: Daniel L
authors: DL
authors: Dries
authors: Steven G
authors: SG
authors: Coca
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D059347:Cardio-Renal Syndrome / Q000175:diagnosis / Q000209:etiology / Q000401:mortality*; D004656:Enalapril / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril