Angiotensin Receptor-Neprilysin Inhibition in Heart Failure

Abstract This chapter appraises the PARADIGM-HF trial, which compared sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor, with enalapril in treating heart failure with reduced ejection fraction (HFrEF). The trial showed that sacubitril-valsartan significantly reduces cardiovascular deaths and hospitalizations compared to enalapril and improves patient-reported symptoms and physical limitations. Although sacubitril-valsartan led to higher rates of adverse events such as hypotension and hyperkalemia, it resulted in fewer treatment discontinuations due to side effects. The benefits of sacubitril-valsartan were consistent across various subgroups, including patients with milder heart failure. Finally, the chapter discusses sacubitril-valsartan's role as a cornerstone therapy for HFrEF, while acknowledging its limited application in patients with severe comorbidities.