Background:
In patients with heart failure, chronic kidney disease (CKD) is associated with a higher risk of renal events than in patients without CKD, irrespective of the ejection fraction. We assessed the renal effects of angiotensin/neprilysin inhibition in patients with heart failure in a pooled analysis of 13,195 patients with reduced and preserved ejection fraction.
Methods:
We combined data from PARADIGM-HF (LVEF eligibility≤40%; n=8,399) and PARAGON-HF (LVEF eligibility≥45%; n=4,796) in a prespecified pooled analysis. We assessed the effect of treatment (sacubitril/valsartan compared with enalapril or valsartan) on the renal composite outcome, defined as the time to first occurrence of either: ≥50% reduction in eGFR, end-stage renal disease, or death from renal causes. We also assessed the influence of therapy on eGFR slope.
Results:
At randomization, eGFR was 68±20 ml/min/1.73m
2
in PARADIGM-HF and 63±19 ml/min/1.73m
2
in PARAGON-HF. The composite renal outcome occurred in 70 of the 6594 patients (1.1%) in the sacubitril/valsartan group and 123 of the 6601 patients (1.9%) in the valsartan or enalapril group, with a risk reduction of 44% (HR 0.56, 95%CI 0.42-0.75; P<0.001). The treatment effect on the composite renal endpoint did not differ according to the baseline eGFR (<60 vs ≥ 60 ml/min/1.73 m
2
; P-interaction=0.46) or baseline ejection fraction (P-interaction=0.35). From randomization, the mean decline in eGFR was -1.8 (95%CI -1.9 to -1.7) ml/min/1.73 m
2
per year for the sacubitril/valsartan group, compared with -2.4 (95%CI -2.5 to -2.2) ml/min/1.73 m
2
per year for the valsartan or enalapril group, with an adjusted mean difference of 0.6 (95%CI 0.4 to 0.7; P<0.001) ml/min/1.73 m
2
per year.
Conclusions:
In patients with heart failure, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, compared with valsartan or enalapril, across the spectrum of ejection fraction.
Heart failure with improved ejection fraction: A review and pooled analysis of pathophysiology, diagnosis and clinical management
