KI Video Abstract: Acute declines in estimated glomerular filtration rate on enalapril and mortality and cardiovascular outcomes in patients with heart failure with reduced ejection fraction
ISN Academy. McCallum W. 10/21/19; 285192
Wendy McCallum
Wendy McCallum
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Angiotensin-converting enzyme inhibitors (ACEI) are beneficial in patients with heart failure with reduced ejection failure (HFrEF) but are associated with acute declines in eGFR. The threshold of acute eGFR decline that can be tolerated after initiation of an ACEI has been difficult to evaluate, because of the challenge of how to account for medication-driven eGFR declines.

Using the Studies of Left Ventricular Dysfunction (SOLVD) trials (n=6245), Cox proportional hazards regression models were used to calculate hazard ratios of all-cause mortality and heart failure (HF) hospitalization associated with %eGFR decline at 2-weeks and 6-weeks after randomization to enalapril versus placebo.

​In a magnified estimate, where %eGFR decline on enalapril was examined in reference to equal %eGFR decline on placebo, any eGFR decline in the enalapril arm was associated with lower hazard of both outcomes. Under a conservative estimate using 0% eGFR decline in the placebo arm as the reference, up to a 10% decline with enalapril was associated with mortality benefit (HR=0.87 [0.77, 0.99]) while up to a 35% decline was associated with decreased risk of HF hospitalization (HR=0.78 [0.61, 0.98]). Under the intermediate estimate where the reference group was half of the degree of %eGFR decline on placebo, up to a 15% decline with enalapril was associated with a mortality benefit (HR=0.86 [0.77, 0.97] and all levels of eGFR decline were associated with decreased risk of HF hospitalization. There was no %eGFR decline, including up to 40%, in any of these models at either 2-weeks or 6-weeks where enalapril was associated with higher mortality risk. In patients with HFrEF, enalapril is associated with decreased risk of mortality and HF hospitalizations, and compelling reasons beyond moderate eGFR decline ought to be considered before its use is withdrawn.

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