Determinants and Consequences of Renal Function Variations with Aldosterone Blocker Therapy in Heart Failure Patients Post Myocardial Infarction. Insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS)
Background—We evaluated the effect of the selective mineralocorticoid receptor antagonist, eplerenone, on renal function and the interaction between changes in renal function and subsequent cardiovascular (CV) outcomes, in patients with heart failure (HF) and left ventricular systolic dysfunction due to an acute myocardial infarction (AMI) in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS).
Methods and Results—Serial changes in estimated glomerular filtration rate (eGFR) were available in 5792 patients during a 24-month follow-up. Patients assigned to eplerenone had a decline in eGFR with an adjusted mean difference of -1.4±0.3 ml/min/1.73m2 compared with placebo (p<0.0001), an effect that appeared within the first month (-1.3±0.4 ml/min/1.73m2) and persisted throughout the study. Overall, 914 patients experienced a decline in eGFR > 20% in the first month, respectively 16.9% and 14.7% in the eplerenone and placebo groups (OR=1.15[1.02-1.30]; p=0.017). In multivariate analyses, determinants of this early decline in eGFR were female sex, age ≥ 65 yr, smoking, left ventricular ejection fraction < 35%, eplerenone and loop diuretic use. An early decline in eGFR by > 20% was associated with worse CV outcomes, independent of baseline eGFR and of the use of eplerenone which retained its prognostic benefits even under these circumstances.
Conclusions—In patients with HF after AMI and receiving standard medical care, an early decline in eGFR is not uncommon and is associated with poor long-term outcome. Eplerenone induced a moderately more frequent early decline in eGFR, which did not affect its clinical benefit on CV outcomes.
- Received March 25, 2011.
- Accepted November 16, 2011.
- Copyright © 2011, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited