Ten Years Real-World Experience With Sacubitril/Valsartan in Patients With Heart Failure With Reduced Ejection Fraction

Abstract Aims To provide a comprehensive overview of real-world evidence (RWE) regarding the implementation, clinical effectiveness, and safety of Sacubitril/valsartan (Sac/Val) in patients with Heart Failure (HF) with reduced ejection fraction (HFrEF). Methods A systematic literature search of PubMed was conducted through March 2024 following PRISMA guidelines. Results The review included 45 manuscripts from 30 different studies, primarily from Europe (44%) and the US (30%). RWE confirmed that Sac/Val was associated with a lower risk of cardiovascular mortality (10%-16%), HF hospitalization (10%-38%), and all-cause mortality (10%-25%). Sac/Val was significantly associated with cardiac reverse remodeling and lower-grade mitral regurgitation. Despite these benefits, implementation gaps persist, with only 15%-25% of patients achieving target doses in clinical practice. The most common reported adverse event with Sac/Val was hypotension (up to 17.6%), though severe hyperkalemia and renal decline were similar when compared with traditional renin angiotensin system inhibitors. Conclusion Real-world data mirror the efficacy and safety profiles seen in randomized controlled trials, establishing Sac/Val as a cornerstone of HFrEF therapy. However, significant barriers remain, including delayed initiation and suboptimal dose titration. Enhancing clinician and patient awareness is needed to bridge these implementation gaps and fully realize the drug's potential to reduce the global healthcare burden of HF.