Comparison of Efficacy and Safety of Angiotensin Receptor-Neprilysin Inhibitors in Patients With Heart Failure With Reduced Ejection Fraction: A Meta-Analysis

The present meta-analysis was conducted to compare the safety and efficacy of angiontensin receptor neprilysin inhibitor (ARNI) with angiotensin receptor blockers (ARBs) and angiotensin-converting-enzyme inhibitors (ACEi) in patients with heart failure with reduced ejection fraction (HFrEF). This meta-analysis was conducted and reported in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Two authors carried out a scientific literature search on online databases, including EMBASE, PubMed, and the Cochrane Library. The following keywords or corresponding Medical Subject Headings (MeSH) were used for the search of relevant articles: "heart failure with reduced ejection fraction," "angiotensin receptor-neprilysin inhibitor," "Angiotensin receptor blockers," and "clinical outcomes." Outcomes assessed in the present meta-analysis included changes in ejection fraction (EF) from baseline in percentage. Other outcomes assessed in the present meta-analysis included all-cause mortality, cardiovascular death, and hospitalization due to heart failure. Adverse events assessed in the present meta-analysis included hypokalemia, acute kidney injury, and hypotension. Total 10 studies were included. This meta-analysis showed that treatment with ARNI was associated with a significantly lower risk of all-cause mortality and cardiovascular death compared to control groups. There was no significant difference between the two groups in terms of change of EF from baseline or hospitalization related to heart failure. However, the risk of hypotension was significantly higher in patients receiving ARNI. The study findings support the use of ARNI as first-line therapy for heart failure with reduced ejection fraction. Further studies are required to determine the optimal use of ARNI in heart failure management and to investigate the mechanisms underlying the increased risk of hypotension.