Efficacy and Safety of Sacubitril/Valsartan in the Management of Heart Failure with Preserved Ejection Fraction: A Comprehensive Review

Heart failure with preserved ejection fraction (HFpEF) represents a significant clinical challenge due to its complex pathophysiology, limited therapeutic options, and growing prevalence, particularly in aging populations. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), has emerged as a potential therapeutic intervention in HFpEF. While sacubitril/valsartan has demonstrated substantial benefits in heart failure with reduced ejection fraction (HFrEF), its role in HFpEF has been the subject of extensive clinical investigations. This review aims to evaluate the efficacy, safety, and clinical implications of sacubitril/valsartan in the treatment of HFpEF. We will discuss the pharmacological mechanisms of the ARNI combination, key clinical trials, and their outcomes, including the PARAGON-HF trial, and assess its impact on morbidity, mortality, functional status, and quality of life in HFpEF patients. Additionally, we will explore potential biomarkers for response to therapy and the relevance of phenotyping HFpEF subgroups to optimize therapeutic strategies.