29 July 2020
With an estimated 6.2 million adults affected in the USA, heart failure remains a leading cause of morbidity, mortality, and health-care costs, despite the use of guideline-based medical therapies. The search for a more efficient therapy was rekindled when findings from the Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial demonstrated evidence for cardiovascular and mortality benefit of sacubitril/valsartan, a dual angiotensin receptor blocker and neprilysin inhibitor (ARNI), over enalapril (an angiotensin-converting enzyme inhibitor) in patients with heart failure and reduced rjection fraction (HFrEF). Following the trial’s compelling results, recommendations for the use of sacubitril/valsartan as a replacement for an angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker were incorporated into the 2016 American College of Cardiology (ACC), the American Heart Association (AHA), and the Heart Failure Society of America recommended (HFSA) guidelines for the management of heart failure. This review aims to gain insight into the benefits as well as limitations associated with the use of sacubitril/valsartan in the treatment of heart failure (HF) through exploration of various subgroup analyses of the PARADIGM-HF trial, subsequent retrospective analyses, and randomized controlled trials that followed this landmark trial.