Mo471use of Sacubitril/Valsartan in Patients With Chronic Kidney Disease: A New Approach

Abstract

Background and Aims Neprilysin inhibition (NEPi) combined with a renin-angiotensin system (RAS) blocker has been shown to play an important role among patients with heart failure (HF), whose main cause of inpatient admission is congestion, reducing effectively HF hospitalization and cardiovascular death. These benefits stem from NEPi being a natriuresis and diuresis factor while RAS, which activates subsequently, staying blocked. Thanks to this, sacubitril/valsartan is a promising tool targeting patients with chronic kidney disease (CKD) and HF, which frequently coexist and lead one to the other, challenging their management. There is evidence NEPi-RASb may be beneficial in this population but long-term outcome still lacks. The primary aim is to analyse potential improvement in HF and advanced CKD. Secondary, to evaluate the tolerability and safety profile in this population. Method A prospective observational study, conducted from October 2016 to December 2020. Twenty-five patients were included meeting the following criteria: diagnosis of HF plus reduced left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional class of II-IV with indication of sacubitril/valsartan, and CKD stages 3-4. All of them were followed periodically by a Nephrologist at our Department. Results The male:women ratio was 4:21, with a mean age of 73.2 ± 5.9 years. All patients had diagnosed hypertension, 32% type 2 diabetes, and 92% dyslipidemia. By December 2020, seven patients had completed three-year follow-up, whereas 17 were followed successfully through one year of treatment. Six patients died during the study (50% due to cardiovascular event, none due to renal malfunction), another discontinued treatment due to hypotension, and no patient started renal replacement therapy. The median of the studied time of treatment was 31 months (IQR 23.5 - 35). Cardiac and renal characteristics are listed in Table 1. At first year a significant improvement in LVEF was found (p=0.018). Although it is observed a tendency to this enhancement at second and third years, statistical analysis was not significative, arguably because a limited sample. Nonetheless, the number of visits to the Emergency Department (ED) regarding congestion symptoms were significantly reduced at these periods. More interesting, kidney function improved at first year when comparing serum creatinine (p=0.043) and eGFR (p=0.008), and this improvement stays in the long term at second and third years (p=0.019, p=0.046 respectively). There were no significant changes in potassium nor in blood pressure, still urine protein excretion was significantly higher at third year (p=0.043), understandable possibly due to hyperfiltration mechanisms and diabetic nephropathy progression. Conclusion Sacubitril/valsartan showed a long-term improvement in cardiac and kidney function, explaining a reduction in the number of visits to ED due to congestion and eventually a better quality of life. Besides, the improvement in kidney function cannot be totally understood in the context of enhanced LVEF at first year as this effect fades with time. Future research should explore this line.