Patients With HFpEF Administered Sacubitril/Valsartan Gain Renal Benefits

Study results from Taiwan, conducted among patients with heart failure and comorbid chronic kidney disease, are showing a drop in the risk of renal function decline among patients with heart failure with preserved ejection fraction (HFpEF) administered sacubitril/valsartan. These findings appeared in a recent issue of Scientific Reports.

The combination neprilysin inhibitor/angiotensin II receptor blocker, sold as Entresto by Novartis, recently became the first medication specifically approved by the FDA to treat HFpEF.

“Sacubitril/valsartan is a combined neprilysin inhibitor/angiotensin II receptor blocker designed for treatment of heart failure,” the study authors wrote. “Nonetheless, its renal protective effect remained an issue of debate.”

In providing background for their study, the researchers noted that a separate study from the United States showed 61.9% of patients with heart failure had at least 1 noncardiovascular-related hospitalization, “showing an important role of noncardiac comorbidities in HF patients.”

Their retrospective cohort study, which took place between January 1, 2016, and October 31, 2018, comprised 274 patients from Wanfang Hospital, Taipei Medical University (sacubitril/valsartan, n = 137; valsartan only, n = 137; mean [SD] age, 72.7 [14.9] years; 65.7% male) matched 1:1 on gender, age, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LVEF). The mean baseline mean eGFR was 70.9 (24.7) mL/min/1.73 m² and mean LVEF, 54.0% (15.7%). The study end point was sacubitril/valsartan or valsartan stoppage and all-cause death.

During the 18-month follow-up period—with measures taken at 3, 6, 12, and 18 months—the primary outcomes were end eGFR, renal function decline (drop of ≥ 20% in eGFR), mortality, and heart failure–related hospitalization. There was a significantly greater improvement overall in eGFR in the sacubitril/valsartan group vs the valsartan-only group (P < .01) and among the subgroup of patients with HFpEF (LVEF ≥ 40%) or the participants who had a baseline eGFR of ≥ 60 mL/min/1.73 m².

Risks of cardiovascular mortality, all-cause mortality, or heart failure–related mortality did not change.

However, renal function decline risk was halved (HR, 0.5; 95% CI, 0.3-0.9), and the authors called this a significant reduction, following a multivariate Cox regression analysis.

Analyses produced the following results by the 18-month mark:

• eGFRs of 69.4 and 63.9 mL/min/1.73 m² in the sacubitril/valsartan and valsartan-only groups
• 7.2 mL/min/1.73 m² (95% CI, 2.9-11.5) higher eGFR, via generalized estimating equation, in the sacubitril/valsartan group compared with the valsartan-only group (P < .01)
• Among patients with HFpEF, an 8.2 mL/min/1.73 m² (95% CI, 3.8-12.6) higher eGFR compared with the valsartan-only group (P < .01)
• For patients with a baseline eGFR of ≥ 60 mL/min/1.73 m², an 8.0 mL/min/1.73 m² (95% CI, 1.3-14.6) higher eGFR in the sacubitril/valsartan vs the valsartan-only group (P = .02)
• For patients with a baseline eGFR of < 60 to ≥ 30 mL/min/1.73 m², a 12.7 mL/min/1.73 m² (95% CI, 5.7-19.8) higher eGFR in the sacubitril/valsartan vs the valsartan-only group (P < .01)
• No change in LVEF, hemoglobin, or serum creatinine levels between the groups for the duration of the study.
• No significant improvement in eGFR among patients with heart failure with reduced ejection fraction (LVEF < 40%) or a baseline eGFR < 30 mL/min/1.73 m².

The authors attribute the renal protective effect seen to neprilysin inhibition, and they highlight that this “may be restricted to patients with HF, especially in those with HFpEF,” but that future studies should confirm these findings among patients susceptible to the benefits of sacubitril/valsartan.

The retrospective study design, lack of data on albumineria as an outcome variable, small case number, and including only patients of Asian ethnicity mark limitations to these findings.

Reference

Hsieh H-L, Chen C-Y, Chen C-H, et al. Renal protective effect of sacubitril/valsartan in patients with heart failure. Sci Rep. Published online February 25, 2021. doi:10.1038/s41598-021-84118-8