Sacubitril/Valsartan Off-Label Uses for Heart Failure

•Sacubitril/valsartan can be used in inpatients who are hemodynamically stable after acute decompensated heart failure.•There is no compelling indication to use sacubitril/valsartan rather than angiotensin receptor-neprilysin inhibitors in patients with acute coronary syndrome with left ventricular ejection fraction ≤ 40%.•Sacubitril/valsartan may be indicated in patients with left ventricular assist devices or chemotherapy-induced cardiomyopathy or patients with heart failure who are on dialysis. Sacubitril/valsartan is an angiotensin receptor/neprilysin inhibitor that the Food and Drug Administration has indicated to reduce the risk of cardiovascular hospitalization and death in patients with left ventricular ejection fraction below normal and with no specified ejection-fraction cut-off. However, clinically significant patient groups were excluded or minimally represented in sacubitril/valsartan's pivotal clinical trials. Clinicians often encounter scenarios in which a sacubitril/valsartan off-label use may be beneficial, but limited resources are available to evaluate the efficacy and safety in these patients. This state-of-the-art review describes contemporary literature for sacubitril/valsartan Food and Drug Administration off-label indications to help clinicians assess its appropriateness in these selected, clinically important groups of patients: those with acute decompensated heart failure, acute coronary syndrome, peripartum cardiomyopathy, chemotherapy-induced cardiomyopathy, adult congenital heart disease, cardiomyopathy in dialysis patients, right ventricular failure, or durable left ventricular assist device.