For heart failure patients with reduced ejection fraction (HFrEF), sacubitril/valsartan helped preserve kidney function, as assessed by estimated glomerular filtration rate (eGFR), according to a post hoc analysis of a pivotal study.

The original Phase III heart failure study, PARADIGM-HF, showed that treatment with sacubitril/valsartan reduced the risk of dying from a cardiovascular cause by 20%, reduced heart failure hospitalizations by 21% and reduced the risk of dying from any cause by 16%, as compared to enalapril. Now, a new analysis published in The Lancet Diabetes & Endocrinology, demonstrated significant benefits of the treatment related to kidney function.

Physicians interview dialysis patient. (Source: 15th Wing Air Force)

Compared to those treated with the ACE inhibitor enalapril, HFrEF patients treated with sacubitril/valsartan had a slower rate of decline in eGFR. In fact, for a sub group of patients who had both HFrEF and diabetes, the magnitude of benefit was twice as high, according to the analysis.

The findings are especially significant because as many as 40% of HF patients have diabetes, which is associated with greater risk of developing chronic kidney disease, which can also lead to worse cardiovascular outcomes.

“For patients in whom the renin-angiotensin system is already maximally blocked, the addition of neprilysin inhibition attenuates the effect of diabetes to accelerate the deterioration of renal function that occurs in patients with chronic heart failure,” the Baylor University Medical Center-led researchers wrote.

The randomized, double-blind PARADIGM-HF trial compared the effects of sacubitril/valsartan (97 mg/103 mg twice daily) with enalapril (10 mg twice daily) in 8,399 patients with mild-to-moderate chronic heart failure and systolic dysfunction.

For the secondary intention-to-treat analysis, the study team assessed the change in estimated glomerular filtration rate (eGFR) over a 44-month follow-up period in 3,784 patients with type 2 diabetes and 4,615 patients without.

The study determined that eGFR decreased by 1·1 mL/min per 1·73 m² per year (95% CI 1·0–1·2) in patients without diabetes, but by 2·0 mL/min per 1·73 m² per year (1·9–2·1) in those with diabetes (p<0·0001).

“Compared with patients treated with enalapril, those treated with sacubitril/valsartan had a slower rate of decline in eGFR (−1·3 vs −1·8 mL/min per 1·73 m² per year; p<0·0001), and the magnitude of the benefit was larger in patients with versus those without diabetes (difference 0·6 mL/min per 1·73 m² per year [95% CI 0·4–0·8] in patients with vs 0·3 mL/min per 1·73 m² per year [0·2–0·5] in those without diabetes; p_interaction=0·038).,” the researchers wrote.

Researchers added that the expanded effect of neprilysin inhibition in patients with diabetes could not be explained by the effects of treatment on the course of heart failure or on HbA_1c. The incremental benefit of sacubitril/valsartan in patients with diabetes was no longer apparent when changes in eGFR were adjusted for urinary cyclic guanosine monophosphate (p=0·41), researchers also wrote.