The Safety and Efficacy of the Early Use of Sacubitril/Valsartan After Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials

Abstract

Acute myocardial infarction (AMI) is a significant global cause of mortality, necessitating the exploration of innovative treatments against the condition. Angiotensin receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor-neprilysin inhibitors (ARNIs) such as sacubitril/valsartan have demonstrated promise in managing acute heart failure (HF). However, despite favorable evidence from clinical trials for the use of sacubitril/valsartan in AMI, its overall efficacy remains a subject of debate. Hence, we conducted this review and meta-analysis, by adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and aligned with European Society of Cardiology recommendations, to compare sacubitril/valsartan with traditional ACEI/ARB treatments for AMI. We employed Review Manager 5.4 for statistical analysis, the Risk of Bias Tool 2.0 was utilized for quality assessment, and publication bias was assessed using a funnel plot. A p-value <0.05 was considered statistically significant. Eight randomized controlled trials (RCTs) were included in this meta-analysis. Our findings revealed that participants treated with sacubitril experienced significantly improved outcomes in terms of HF (OR=0.79; 95% CI: 0.66-0.95; p=0.01; I²=23%), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (MD = -1.58; 95% CI: -1.78 to -1.37, p<0.00001; I²=97%), and major adverse cardiovascular events (MACE) (OR=0.84; 95% CI: 0.72-0.99; p=0.03; I²=44%). However, left ventricular ejection fraction (LVEF) (MD=3.68; 95% CI: 3.35-4.01, p<0.00001; I²=71%) showed greater improvement in the control group compared to the experimental group. Our meta-analysis suggests that sacubitril offers a favorable balance between safety and effectiveness. Sacubitril significantly improved outcomes in terms of HF, MACE, and NT-proBNP levels when compared to the control group. However, improvement in LVEF was notably higher in the control group over the sacubitril/valsartan group.

Keywords: acute myocardial infarction; early use; efficacy; meta-analysis; randomized controlled trials; sacubitril/valsartan; safety.

Figure 1. Quality assessment

Figure 2. Funnel plot for the outcome of HF

HF: heart failure

Figure 3. PRISMA flow diagram illustrating the selection of studies

PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analysis

Figure 4. Forest plot for the outcome of LVEF

LVEF: left ventricular ejection fraction

Figure 5. Sensitivity analysis for the outcome of LVEF

LVEF: left ventricular ejection fraction

Figure 6. Forest plot for the outcome of NT-proBNP

NT-proBNP: N-terminal pro–B-type natriuretic peptide

Figure 7. Forest plot for the outcome of HF

HF: heart failure

Figure 8. Forest plot for the outcome of MACE

MACE: major adverse cardiovascular events