Heart failure with reduced ejection fraction remains a prevalent clinical syndrome associated with significant morbidity and mortality. Despite significant advances in heart failure with reduced ejection fraction pharmacotherapy, 5-year mortality remains 50%. Sacubitril/valsartan is a first-in-class angiotensin-receptor-neprilysin inhibitor, Food and Drug Administration–approved to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure with reduced ejection fraction. Sacubitril/valsartan is recognized as a significant therapeutic advancement and endorsed by national guidelines, yet adoption into clinical practice has lagged across the United States. Recommendations for use differ greatly between the Prospective Comparison of Angiotensin-Receptor-Neprilysin Inhibitor with Angiotensin-Converting-Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure clinical trial, international guidelines, and the Food and Drug Administration-approved labeling, which can lead to uncertainty with prescribing. It is essential to establish an evidence-based, pragmatic approach to patient selection and management of sacubitril-valsartan facilitate integration into clinical practice. This review summarizes the pharmacology of sacubitril/valsartan, its known benefits and risks, and important considerations for incorporating sacubitril/valsartan into chronic heart failure management.
Magnesium Dynamics and Sympathetic Nervous System Activity in Patients With Chronic Heart Failure
