Efficacy of early angiotensin receptor/neprilysin inhibition in post-myocardial infarction patients: a meta-analysis of randomized controlled trials

Background Early intervention with angiotensin receptor/neprilysin inhibitors (ARNI) following acute myocardial infarction (AMI) has emerged as a promising strategy to improve cardiac outcomes in high-risk patients. Although ARNI has demonstrated significant benefits in chronic heart failure, its early application in post-AMI patients—particularly those with left ventricular (LV) dysfunction and symptomatic heart failure—remains underexplored. Furthermore, the potential synergy between ARNI therapy and successful percutaneous coronary intervention (PCI) merits investigation. Purpose To determine whether early ARNI administration improves cardiac remodeling and clinical outcomes compared to ACEi/ARBs in high-risk AMI patients and assess geographical variations in treatment responses. Methods We performed a meta-analysis of 13 randomized controlled trials, comprising a total of 7,309 patients, to compare early ARNI treatment with standard ACE inhibitor/angiotensin receptor blocker (ACEI/ARB) therapy in high-risk post-AMI patients. Primary outcomes included changes in LV ejection fraction (LVEF) and levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), while secondary outcomes comprised heart failure hospitalization, cardiovascular death, and all-cause mortality. A random-effects model was employed for pooled analyses, and meta-regression was conducted to evaluate the impact of PCI on treatment efficacy. Results Our results indicate that early ARNI therapy significantly improved LVEF (mean difference of approximately +2.5%; 95% CI: +1.3 to +3.7) and reduced NT-proBNP levels (mean difference of approximately –446 pg/mL) compared with ACEI/ARB therapy. Moreover, ARNI treatment was associated with a markedly lower risk of heart failure hospitalization (risk ratio around 0.55), although no significant differences were observed in cardiovascular or all-cause mortality between the groups. Importantly, meta-regression analysis revealed that for every 1% increase in the proportion of patients receiving PCI at admission, the LVEF improvement with ARNI increased by approximately 0.397% (p = 0.002), suggesting a synergistic effect between PCI and ARNI therapy. These benefits were consistently observed across both Asian and non-Asian populations. Conclusions Early ARNI administration in high-risk post-AMI patients enhances cardiac function and reduces heart failure events when compared to conventional ACEI/ARB therapy. The additional benefit observed with concomitant PCI underscores the potential for a synergistic treatment approach. These findings support the integration of early ARNI therapy into post-AMI management, while future studies should further validate long-term outcomes and explore its efficacy across diverse patient populations.