Sacubitril/Valsartan in Heart Failure Hospitalization: Two Pills a Day to Keep Hospitalizations Away?

Heart failure (HF) is a clinical syndrome with signs and symptoms that result from any structural or functional deterioration of ventricular filling or ejection of blood. It is the final stage of various cardiovascular diseases (e.g., coronary artery disease, hypertension, previous myocardial infarction) and remains one of the leading causes of hospitalization. It poses severe health and economic burden worldwide. Patients usually present with shortness of breath due to impaired cardiac ventricular filling and decreased cardiac output. Cardiac remodeling due to the renin-angiotensin-aldosterone system overactivation is the final pathological mechanism leading to these changes. The natriuretic peptide system is also activated to stop the remodeling. Sacubitril/valsartan, an angiotensin-receptor neprilysin inhibitor, has prompted a substantial conceptual change in HF treatment. Its primary mechanism is the inhibition of cardiac remodeling and the prevention of natriuretic peptide degradation by inhibiting the enzyme neprilysin. It is an efficacious, safe, and cost-effective therapy that improves the quality of life and survival rate in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction. It has been demonstrated to significantly reduce hospitalization rates and rehospitalization for HF when compared to enalapril. In this review, we have discussed the benefits of sacubitril/valsartan in treating patients with HFrEF, particularly in reducing hospitalizations and readmissions. We have also compiled studies to examine the drug's effect on adverse cardiac events. Finally, the cost benefits of the drug and optimal dosing strategies are also reviewed. Our review article, combined with the recommendations of the 2022 American Heart Association guidelines for heart failure, strongly suggests that sacubitril/valsartan is a cost-effective strategy that reduces hospitalizations for HFrEF patients when started early with optimal doses. There is still much uncertainty regarding the optimal usage of this drug, its use in HFrEF, and the cost benefits when used alone compared with enalapril.