Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, and has been recently indicated as a new treatment option with a strong level of recommendation (class I, level of evidence B) in the main international guidelines. Cardiovascular disease (CVD) is the most common cause of death in end stage renal disease (ESRD) patients undergoing hemodialysis (HD). Hence, treatments to improve mortality and specifically cardiovascular outcomes in this population are greatly needed. So far, no data available about the efficacy and safety of sacubitril/valsartan in ESRD patients undergoing hemodialysis, although this medication was noted to be effective and comparably well tolerable in those with estimated glomerular filtration rate(eGFR) 20 to 60 mL/min/1.73 m2 in the United Kingdom Heart and Renal Protection-III trial.

The purpose of this open label, randomized controlled study with prospective data collection is to assess the efficacy and safety of sacubitril/valsartan in maintenance hemodialysis patients with heart failure.

Inclusion Criteria:

• Written informed consent obtained before any study assessment is performed.
• End stage renal disease (ESRD) patients (eGFR<15ml/min/1.73m² as measured by the Chronic Kidney Disease Epidemiology Collaboration formula at screening) who have been receiving hemodialysis 3 times a week for at least 12 weeks before registration.
• Chronic heart failure (NYHA class ≥ II) with reduced ejection fraction, defined as known LVEF ≤ 50%.
• Mean sitting systolic blood pressure(msSBP)≥110 mmHg.
• Use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker for at least 2 weeks.
• Good compliance.

Exclusion Criteria:

• Acute renal failure with hemodialysis.
• Isolated right heart failure owing to pulmonary disease, primary cause of dyspnea due to noncardiac, non-HF causes such as acute or chronic respiratory disorders.
• Systolic blood pressure lower than 100 mmHg at screening (<95 mmHg at the randomization visit).
• Previous history of intolerance to recommended target doses of angiotensin receptor blockers.
• Significant laboratory abnormalities at screening interfering with assessment of study drug safety or efficacy (such as serum potassium>5.5 or <3.5mmol/L, serum sodium<130mmol/L or alanine aminotransferase or aspartate aminotransferase>2 times the upper limit of the normal range)
• History of hypersensitivity to any of the study drugs or their excipients or to drugs of similar chemical classes.
• History of angioedema.
• Any medications that have potential for drug-drug interaction with LCZ696 will not be allowed during the study.
• Pregnant female.
• Use of sacubitril/valsartan prior to week-2.