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Circ Heart Fail. 2011 Nov;4(6):685-91. doi: 10.1161/CIRCHEARTFAILURE.111.963256. Epub 2011 Sep 8.

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

Author information

  • 1Cardiovascular Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA. jeffrey.testani@uphs.upenn.edu

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.

METHODS AND 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.

PMID:
21903907
[PubMed - indexed for MEDLINE]
PMCID:
PMC3248247
Free PMC Article
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