Angiotensin-Neprilysin Inhibition in Hemodialysis Initiation

Eligibility Criteria

• * Adults ≥18 years initiating HD (within 90 days of first HD session)
• * Thrice-weekly HD
• * Informed consent
• * Hemodynamically Stable: Sitting pre-dialysis SBP ≥110 mmHg averaged over prior two weeks or at the baseline visit; no symptomatic hypotension in prior two weeks; no use of midodrine.
• * Has not taken an ACEi for 36 hours prior to randomization
• * Anuria (daily urine volume \<100 mL/day)
• * Current or any use of sacubitril/valsartan within the past 30 days
• * History of hypersensitivity or intolerance to any of the study drugs, including ARBs or sacubitril/valsartan
• * Angioedema related to previous ACE inhibitor, ARB, or ARNI therapy
• * Serum potassium \>5.5 mEq/L at screening (pre-HD if already on HD)
• * Acute coronary syndrome, stroke, TIA, major CV surgery, percutaneous coronary intervention or carotid angioplasty within one month
• * Intended coronary or carotid revascularization within 4 months
• * Implantation of a cardiac resynchronization therapy device (CRTD) within 3 months or intent to implant a CRTD
• * History of heart transplant, or planned heart transplant, or with left ventricular assist device
• * Planned renal transplant within 4 months
• * Documented untreated ventricular arrhythmia with syncopal episodes within 3 months
• * Symptomatic bradycardia or 2nd or 3rd degree heart block without a pacemaker
• * Presence of hemodynamically significant valvular disease or hypertrophic cardiomyopathy or infiltrative cardiomyopathy including suspected or confirmed amyloid heart disease (amyloidosis)
• * History of malignancy of any organ system within the past year (exceptions: squamous and basal cell carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence)
• * Liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis with evidence of portal hypertension); Alanine aminotransferase (ALT) levels \>2.0 times the upper limit of normal (ULN) or total bilirubin \>1.5 times the ULN, unless consistent with Gilbert's disease
• * Pregnant (positive hCG test) or lactating women
• * Enrollment in another interventional trial
• * Received an active investigational drug (including vaccines) other than a placebo agent, or used an investigational medical device within 12 weeks before Day 1/baseline
• * Does not have capacity to consent (Folstein mini-mental score of 23 or less)
• * Any condition that in the opinion of the investigator would make participation not in the best interest of the subject
• * Women of child-bearing age, unless using two birth control methods. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of investigational drug and for 7 days off of study drug.