Packer M, et al. - Authors evaluated the impacts of neprilysin inhibition on renal function in patients with type 2 diabetes. By the addition of neprilysin inhibition in patients in who have the renin-angiotensin system already maximally blocked, the influence of diabetes to hasten the decline of renal function occurring in patients with chronic heart failure was reduced.

Methods

• Authors 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 in the randomized, double-blind PARADIGM-HF trial.
• They evaluated the change in estimated glomerular filtration rate (eGFR) over a 44-month follow-up period in patients with (n=3,784) and those without (n=4,615) diabetes in this secondary intention-to-treat analysis.

Results

• Findings revealed a decrease in eGFR by 1.1 mL/min per 1.73 m²per year (95% CI 1.0–1.2) in patients without diabetes, but by 2.0 mL/min per 1.73 m²per year (1.9-2.1) in those with diabetes (p < 0.0001).
• As per data, those treated with sacubitril/valsartan had a slower rate of decline in eGFR (-1.3 vs -1.8 mL/min per 1.73 m²per year; p < 0.0001) vs patients treated with enalapril, and the scale of the benefit was larger in patients with vs those without diabetes (difference 0.6 mL/min per 1.73 m²per year [95% CI 0.4–0.8] in patients with vs 0.3 mL/min per 1.73 m²per year [0.2-0.5] in those without diabetes; p_interaction=0.038).
• In patients with diabetes, the greater effect of neprilysin inhibition could not be explained by the effects of treatment on the course of heart failure or on HbA_1c.
• Results demonstrated that in patients with diabetes, the incremental benefit of sacubitril/valsartan was no longer apparent when changes in eGFR were adjusted for urinary cyclic guanosine monophosphate (p=0.41).