The Efficacy of Angiotensin Receptor-Neprilysin Inhibitor Versus Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Post Myocardial Infarction: A Meta-Analysis

Abstract

Acute myocardial infarction (MI) is one of the leading global healthcare emergencies, contributing to over three million global deaths. The purpose of this study is to investigate further the efficacy of sacubitril/valsartan over angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in reducing the risk of heart failure (HF) in post-MI patients and providing a clear evidence-based medicine guideline for future use. An electronic database search was conducted on English databases. Eight articles were included, fulfilling our inclusion criteria, i.e., adult patients of ≥18 years with a recent diagnosis of acute MI. Pooled analysis was done using Review Manager version 5.4.1 (Cochrane Collaboration, London, England), and the data for each outcome were analyzed as dichotomous variables. A total of eight clinical trials were included in the meta-analysis. Six studies analyzed the sacubitril/valsartan and ACEI combination. The pooled analysis reported a significant increase in the risk of hypotension (relative risk {RR}: 1.29 {1.18, 1.41}) in the sacubitril/valsartan compared to the ACEI alone group. In addition, a significant increase was observed in the left ventricle ejection fraction (LVEF) after using the sacubitril/valsartan combination compared to using ACEI alone (RR: 3.08 {2.68, 4.48}). Furthermore, no significant difference was observed between the groups in terms of mortality rate (RR: 0.86 {0.73, 1.02}), the risk of heart failure (RR: 0.62 {0.39, 1.00}), the frequency of recurrent MI (RR: 0.86 {0.27, 2.76}), and the mean difference of N-terminal pro-B-type natriuretic peptide (NT-proBNP) (weighted mean difference {WMD}: -174.36 {-414.18, 65.46}) between both the groups. However, the sacubitril/valsartan combination proved to be beneficial in significantly reducing the risk of major adverse cardiac events (MACE) (RR: 0.64 {0.48, 0.84}) and rehospitalizations (RR: 0.53 {0.39, 0.71}) as compared to ACEI post MI. Additionally, sacubitril/valsartan and ARB's combination was reported in two studies. This led to a significant decrease in NT-proBNP concentration (WMD: -71.91 {-138.43, -5.39}) post MI in the sacubitril/valsartan combination group compared to the ARB usage alone. However, no significant difference was observed in the improvement of LVEF (WMD: 0.88 {-5.11, 6.87}) between both groups. Although the sacubitril/valsartan combination has no difference in mortality and outcomes compared to ACEI, there is evidence that using it proves to be more beneficial post MI compared to ACEI and ARB usage alone.

Keywords: angiotensin-converting enzyme inhibitors; meta-analysis; mi; myocardial infarction; neprilysin inhibitor.

Figure 1. PRISMA flow chart for the included studies

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

Figure 2. Cochrane risk-of-bias tool for the included RCTs

Source: [10-17] RCTs: randomized controlled trials

Figure 3. Forest plot of improvement in LVEF outcome for sacubitril/valsartan versus ACEI studies

Source: [10-12] ACEI, angiotensin-converting enzyme inhibitor; SD, standard deviation; CI, confidence interval; IV, inverse variance; LVEF, left ventricle ejection fraction; df, degrees of freedom

Figure 4. Forest plot of mortality outcome for sacubitril/valsartan versus ACEI studies

Source: [10,11,15,16] ACEI, angiotensin-converting enzyme inhibitor; CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel

Figure 5. Forest plot of heart failure outcome for sacubitril/valsartan versus ACEI studies

Source: [10,12,15,16] ACEI, angiotensin-converting enzyme inhibitor; CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel

Figure 6. Forest plot of major adverse cardiac event (MACE) outcome for sacubitril/valsartan versus ACEI studies

ACEI, angiotensin-converting enzyme inhibitor; CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel Source: [10-12]

Figure 7. Forest plot of NT-proBNP outcome for sacubitril/valsartan versus ACEI studies

Source: [11,12,15] ACEI, angiotensin-converting enzyme inhibitor; SD, standard deviation; CI, confidence interval; IV, inverse variance; df, degrees of freedom; NT-proBNP, N-terminal pro-B-type natriuretic peptide

Figure 8. Forest plot for sacubitril/valsartan versus ARB N-terminal pro-B-type natriuretic peptide (NT-proBNP) outcome

Source: [14,17] ARB, angiotensin receptor blocker; SD, standard deviation; CI, confidence interval; IV, inverse variance; df, degrees of freedom

Figure 9. Forest plot for sacubitril/valsartan versus ARB left ventricle ejection fraction (LVEF) outcome

Source: [14,17] ARB, angiotensin receptor blocker; SD, standard deviation; CI, confidence interval; IV, inverse variance; df, degrees of freedom