January 5, 2022European Journal of Heart Failure48 citationsOpen Access
Angiotensin–neprilysin inhibition and renal outcomes across the spectrum of ejection fraction in heart failure
Key Result
In patients with heart failure, sacubitril/valsartan reduced the risk of serious adverse renal outcomes compared with valsartan or enalapril (1.1% vs 1.9%; HR 0.56; 95% CI 0.42–0.75; p<0.001).
Study Design
Type
Meta-Analysis (n=13,195)
Randomization
randomized
Structured PICO
Does sacubitril/valsartan reduce adverse renal outcomes and slow eGFR decline compared to enalapril or valsartan in patients with heart failure across the spectrum of ejection fraction?
P
Population
13,195 patients with heart failure with reduced (EF ≤40%) and preserved (EF ≥45%) ejection fraction from a pooled analysis of the PARADIGM-HF and PARAGON-HF trials.
I
Intervention
Sacubitril/valsartan
C
Comparator
RAS inhibitor (enalapril or valsartan)
O
Outcome
Composite of either ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), or death from renal causescomposite
In patients with heart failure across the spectrum of ejection fraction, sacubitril/valsartan significantly reduced the risk of serious adverse renal outcomes and slowed the decline in eGFR compared with enalapril or valsartan.
Main Result
Hazard Ratio: 0.56 (95% CI 0.42–0.75)
Absolute Event Rate: 1.1% vs 1.9%
p-value: p=< 0.001
Abstract
Abstract Aims Patients with heart failure are at higher risk of progression to end‐stage renal disease (ESRD), regardless of ejection fraction (EF). We assessed the renal effects of angiotensin–neprilysin inhibition in a pooled analysis of 13 195 patients with heart failure with reduced and preserved EF. Methods and results We combined data from PARADIGM‐HF (EF ≤40%; n = 8399) and PARAGON‐HF (EF ≥45%; n = 4796) in a pre‐specified pooled analysis. We assessed the effect of treatment (sacubitril/valsartan vs. enalapril or valsartan) on a composite of either ≥50% reduction in estimated glomerular filtration rate (eGFR), ESRD, or death from renal causes, in addition to changes in eGFR slope. We assessed whether baseline renal function or EF modified the effect of therapy on renal outcomes. At randomization, eGFR was 68 ± 20 ml/min/1.73 m 2 in PARADIGM‐HF and 63 ± 19 ml/min/1.73 m 2 in PARAGON‐HF. The composite renal outcome occurred in 70 of 6594 patients (1.1%) in the sacubitril/valsartan group and in 123 of 6601 patients (1.9%) in the valsartan or enalapril group (hazard ratio 0.56, 95% confidence interval CI 0.42–0.75; p < 0.001). The mean eGFR change was −1.8 (95% CI −1.9 to −1.7) ml/min/1.73 m 2 /year for the sacubitril/valsartan group, compared with −2.4 (95% CI −2.5 to −2.2) ml/min/1.73 m 2 /year for the valsartan or enalapril group. The treatment effect on the composite renal endpoint was not modified by categories of baseline eGFR ( p ‐interaction = 0.64), but was most pronounced in those with baseline EF between 30% and 60% ( p ‐interaction = 0.001). Conclusions In patients with heart failure, sacubitril/valsartan reduced the risk of serious adverse renal outcomes and slowed decline in eGFR, compared with valsartan or enalapril, independent of baseline renal function.