Early in-hospital initiation of angiotensin-receptor–neprilysin inhibitor in post-acute myocardial infarction patients with impaired left ventricular systolic function: a systematic review and meta-analysis of randomized controlled trials

Aims: Heart failure (HF) is a common and serious complication following acute myocardial infarction (AMI), particularly in patients with impaired left ventricular systolic function [left ventricular ejection fraction (LVEF) < 50%] during hospitalization. Although angiotensin-receptor-neprilysin inhibitor (ARNI) therapy has proven benefit in chronic HF, evidence supporting its initiation during the index AMI admission remains limited. This study systematically evaluated the effects of early in-hospital initiation of ARNI therapy compared with angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy on cardiovascular outcomes in post- AMI patients with impaired systolic function. Methods: This systematic review and meta-analysis was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD420251007504). A comprehensive search was completed on 30 August 2025. We included randomized controlled trials (RCTs) enrolling hospitalized AMI patients with impaired systolic function (LVEF <50%) who initiated ARNI therapy during the index admission. The primary outcome was major adverse cardiovascular events (MACEs), defined as HF hospitalization, all-cause mortality, or recurrent acute coronary syndrome. Secondary outcomes included incidence of ventricular arrhythmia, cardiovascular death, stroke, changes in left-ventricular ejection fraction, NT-proBNP levels, and adverse events (AEs). Prespecified subgroup analyses and meta-regression were performed. Results: = 3,768) were included, with a mean follow-up of approximately 6 months. Early in-hospital ARNI initiation significantly reduced MACEs [risk ratio (RR) 0.58; 95% CI 0.41-0.83; number-needed-to-treat (NNT) ≈ 7] and ventricular arrhythmia (RR 0.51; 95% CI 0.35-0.75; NNT ≈ 25). ARNI therapy improved LVEF (mean difference +2.54%; 95% CI +1.34 to +3.75) and reduced NT-proBNP levels (mean difference -424 pg/mL; 95% CI -779 to -68). However, ARNI was associated with higher rates of AEs (RR 1.16; 95% CI 1.14-1.19), primarily symptomatic hypotension (RR 1.32; 95% CI 1.20-1.46). Results were consistent across subgroups, with greater incremental benefit observed among patients who underwent successful primary percutaneous coronary intervention. Conclusions: Among hospitalized post-AMI patients with impaired left ventricular systolic function, early in-hospital initiation of ARNI reduces MACEs, lowers the incidence of ventricular arrhythmia, and improves ventricular function compared with ACEI/ARB therapy, although careful monitoring for hypotension is required. These findings support early in-hospital ARNI adoption in this high-risk population and underscore the need for longer-term outcome studies.