COMPARING SACUBITRIL VALSARTAN AND TRADITIONAL ACE INHIBITORS FOR PREVENTING RECURRENT PULMONARY EDEMA IN HEART FAILURE PATIENTS

Zeeshan Khan, Abdur Rehman Jalali, Syeda Aleezey Jibran, Shaila Alam, Siffat Ullah, Coatsiana Brutus, Mahabuba Sudrul, Dr. Aqsa Islam, Khurram Khan, Tochukwu Anthony Akwue, *Husnain Ramzan, Ayesha Javed, Wasim Shakir

Background: Heart failure (HF) complicated by recurrent pulmonary edema remains a leading cause of emergency hospitalization and cardiovascular mortality worldwide. While ACE inhibitors (ACEi) have been the cornerstone of neurohormonal therapy for decades, the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan has demonstrated superior outcomes in landmark trials. However, a direct comparative analysis focused specifically on recurrent pulmonary edema prevention remains underexplored. Objective: This narrative review compares the efficacy, safety, and mechanistic basis of sacubitril/valsartan versus traditional ACE inhibitors in preventing recurrent pulmonary edema among patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Methods: A structured literature search was conducted across PubMed/MEDLINE and Google Scholar using Boolean search strings. Studies published from 2000 to 2026, with primary emphasis on 2015–2026, were included. Major randomized controlled trials (PARADIGM-HF, PIONEER-HF, PARAGON-HF, TRANSITION, SOLVD, CONSENSUS), meta-analyses, and current guideline documents (2022 ACC/AHA/HFSA, 2021 ESC Heart Failure Guidelines) were synthesized. Key Findings: Sacubitril/valsartan reduced the composite of cardiovascular death and HF hospitalization by 20% (HR 0.80) compared with enalapril in PARADIGM-HF, with a 29% greater reduction in NT-proBNP during acute decompensation in PIONEER-HF. These biomarker and hospitalization benefits translate directly to reduced recurrent pulmonary edema episodes. ACE inhibitors remain effective, guideline-endorsed, and cost-efficient alternatives when ARNI is not tolerated or accessible. Safety profiles are broadly comparable, though sacubitril/valsartan offers a significant advantage in cough reduction and is now preferred by international guidelines for eligible patients. Conclusion: Sacubitril/valsartan represents the preferred pharmacological strategy for recurrent pulmonary edema prevention in HFrEF, surpassing ACE inhibitors across multiple efficacy endpoints. ACE inhibitors retain an important role in practice, particularly in resource-limited settings or ARNI-intolerant patients. Future research should specifically address HFpEF and acute decompensation contexts.