Hindawi

Journal of Healthcare Engineering

Volume 2022, Article ID 7840852, 8 pages
https://doi.org/10.1155/2022/7840852

Review Article
Effects and Safety of Sacubitril/Valsartan for Patients with
Myocardial Infarction: A Systematic Review and Meta-Analysis

Lang Liu,1 Xiaofang Ding,1 Yaxiang Han,1 and Jianfeng Lv 2

1
General Hospital of Ningxia Medical University, Yinchuan City 750000, China
2
Affiliated RenHe Hospital of China, Three Gorges University Second Clinical Medical College of China Three Gorges University,
Yichang City 443000, China

Correspondence should be addressed to Jianfeng Lv; [email protected]

Received 20 October 2021; Revised 19 November 2021; Accepted 27 November 2021; Published 5 January 2022

Academic Editor: Rahim Khan

Copyright © 2022 Lang Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Patients who develop heart failure (HF) after an acute myocardial infarction (AMI) are at higher risk of adverse fatal and nonfatal
outcomes. Studies have shown sacubitril/valsartan can further reduce the risk of cardiovascular death or hospitalization for heart
failure by 20% compared with enalapril. At the same time, its tolerance and safety are better. However, the current evidence
regarding the efficacy of sacubitril/valsartan in patients with heart failure after acute myocardial infarction is controversial. To
assess the effect of sacubitril/valsartan on heart failure after acute myocardial infarction, we conducted a systematic review of the
literature and a meta-analysis of existing randomized clinical trials. Meta-analysis of randomized controlled trails is used where
data are collected from PubMed, the Cochrane library, Embase, and Web of Science. Data about sacubitril/valsartan were available
from 5 studies. Forest plots showed that the sacubitril/valsartan group had a 299% higher value of sacubitril/valsartan to the
control group (MD � 2.99%, 95% CI: 2.01, 3.96, I2 � 78%, P < 0.00001, Figure 2), and the difference was statistically significant.
Forest plots showed that the sacubitril/valsartan group had a 531% lower value of LVEF to the control group (MD � −5.31%, 95%
CI: −7.36, −3.26, I2 � 91%, P < 0.00001, Figure 2), and the difference was statistically significant. Forest plots showed that the
sacubitril/valsartan group had a 133% lower value of NT-proBNP to the control group (MD � −1.33%, 95% CI: −1.54, −1.12,
I2 � 96%, P < 0.00001, Figure 3). Forest plots showed that the sacubitril/valsartan group had a 49% lower risk of heart failure to the
control group (MD � 0.49, 95% CI: 0.27, 0.89, I2 � 0%, P � 0.02, Figure 3). The patients in experimental showed an obviously lower
OR of MACE (OR � 0.47, 95% CI: 0.27, 0.82, P � 0.007, Figure 3). The data were statistically significant. We have observed that for
patients with heart failure after acute myocardial infarction, early administration of sacubitril/valsartan can significantly reduce
the incidence of heart rate, left ventricular ejection fraction, NT-proBNP, and MACE. Our meta-analysis suggests that taking
sacubitril/valsartan is relatively safe and effective, especially if started early after acute myocardial infarction.

1. Introduction significantly lower than before [2]. Although emergency PCI

can revascularize and save part of dying and damaged
Acute myocardial infarction (AMI) refers to the rapid re- myocardium, some patients could still experience left ven-
duction or interruption of coronary blood supply caused by tricular remodeling postmyocardial infarction [3,4]. Ven-
plaque rupture, thrombosis, or coronary artery spasm on the tricular remodeling includes myocardial hypertrophy,
basis of atherosclerosis, resulting in sustained and severe interstitial fibrosis, increased cardiac volume, and reduced
acute ischemia of the corresponding myocardial tissue and diastolic function. LV systolic dysfunction caused by post-
eventually lead to heart muscle cell death disease [1]. In the acute myocardial infarction caused the sympathetic nervous
absence of timely and effective vascular opening, patients die system (SNS) increased excitability, and overactivation of
within a short period of time from malignant arrhythmias, the rennin-angiotensin-aldosterone system (RAAS) pro-
acute heart failure, cardiac rupture, and cardiogenic shock. motes the release of norepinephrine (NE), angiotensin II
In recent years, due to the continuous expansion of chest (II), aldosterone, endothelin, and other vasoconstrictor
pain centers in China, the mortality rate of AMI patients is substances in the circulatory system. At the same time, the
2 Journal of Healthcare Engineering

secretion of the natriuretic peptide system (NPS) synthe- failure after acute myocardial infarction, early administra-
sized by cardiomyocytes themselves to counter the action of tion of sacubitril/valsartan can significantly reduce the in-
the above active substances is absolutely insufficient or cidence of heart rate, left ventricular ejection fraction, NT-
relatively insufficient, resulting in neurohumoral regulation proBNP, and MACE. Our meta-analysis suggests that taking
disorder imbalance, acute hemodynamic disorders, and sacubitril/valsartan is relatively safe and effective, especially
ultimately heart failure [5]. Therefore, early postoperative if started early after acute myocardial infarction.
application of angiotensin-converting enzyme (ACEI) in- The remaining sections and contents are organized as
hibitors or angiotensin receptor blockers, β-blockers, and follows. In subsequent section, proposed methods along
mineralocorticoid antagonist has shown to reduce the risk of with an efficient search method, which is utilized during the
developing HF and death in patients at high risk of devel- proposed study, is described in detail. In Section 3, exper-
oping HF after MI is important [6–12]. imental results and observations were discussed along with
Sacubitril/valsartan is an inhibitor of angiotensin II various issues with the existing state of the art approaches.
receptor enkephalinase (ARNI). It is composed of angio- Finally, concluding remarks along with sufficient future
tensin II receptor blocker (ARB) valsartan and enkephalin directions are provided.
inhibitor (NEPI) precursor AHU377 in a 1 : 1 ratio [13]. On
the one hand, valsartan can block angiotensin type 1 re-
2. Proposed Methods
ceptor (AT1), inhibit the release of Ang II dependent al-
dosterone, and antagonize RAAS. It is beneficial to slow 2.1. Search Strategy. This meta-analysis was performed
down the development of heart failure by reducing sym- according to the Preferred Reporting Items for Systematic
pathetic nerve excitability and myocardial oxygen con- Reviews and Meta-Analyses (PRISMA) guidelines. PubMed,
sumption, improving hemodynamics, and inhibiting Cochrane library, Embase, and Web of Science were used to
myocardial fibrosis [14]. On the other hand, the degradation retrieve all relevant articles with the search terms LCZ696,
of natriuretic peptide system by enkephalinase (NEP) was sacubitril/valsartan, entresto, neprilysin inhibitor, and
inhibited by sacubitril, thus enhancing the natriuretic myocardial infarction. The references of the initial identified
peptide system. For the atrial natriuretic peptide (ANP), literatures were also screen to identify other relevant articles.
brain natriuretic peptide (BNP), and C-type natriuretic The literature search was restricted to English language.
peptide (CNP) system, NPS mainly mediates sodium ex- Patients or the public were not involved in our research.
cretion, diuresis, vasodilation, antagonism against RAAS,
and inhibition of aldosterone secretion by activating
membrane-bound NPS receptor and its second messenger 2.2. Study Selection and Data Extraction. Selection criteria of
loop guanosine monophosphate (cGMP) [15]. Animal ex- various studies are as follows: studies including patients with
periments have shown that [16] ANP inhibits aldosterone- myocardial infarction, studies in the experimental group
mediated myocardial fibrosis and has the effects of sodium including patients administered sacubitril/valsartan, ran-
excretion, diuresis, vasodilation, and heart protection. domized clinical trials are included, and studies with eligible
According to the guidelines for the diagnosis and treatment outcomes.
of acute and chronic heart failure published in ESC in 2016 Exclusion criteria are as follows: we excluded those
[17], ARNI was recommended to replace ACEI/ARB in the studied where randomized control trials are not available
treatment of heart failure patients. and absence of efficacy data and increase in heterogeneity
After the publication of the primary results of PARA- was questionable. For multiple publications that were
DIGM-HF (prospective comparison of angiotensin recep- identified reporting on the same clinical study, the one with
tor-neprilysin inhibitor with ACE inhibitor to determine the most complete publication data was eligible. Any dis-
impact on global mortality and morbidity in heart failure), a crepancies were resolved by discussion. Detailed reviews of
series of subsequent prespecified and post hoc analyses have full-text articles on research design, baseline characteristics,
provided detailed insight into the clinical and quality of life outcomes, and toxicity were completed by Lang Liu and
benefits of sacubitril/valsartan compared to enalapril [11,18]. Peng Bao independently. The publication year, author’s
However, in the latest results of the PARADISE-MI trial name, study design, number of patients, median age,
(prospective angiotensin receptor-neprilysin inhibitor ver- abruption, antepartum hemorrhage, perinatal death, and
sus ACE inhibitor trial to determine superiority in reducing preterm preeclampsia were reported in the articles, and
heart failure events after MI), sacubitril/valsartan has Supplementary Materials were obtained from each included
aroused wide academic discussion. The efficacy of sacubitril/ study (Table 1).
valsartan in acute myocardial infarction has not been clearly
defined, so a large number of clinical trials have been carried
out and achieved certain results. 2.3. Quality Assessment. We assessed the quality of the in-
In this study, we comprehensively searched and sys- cluded literature using the risk of bias in the Cochrane
tematically evaluated the randomized controlled trials of Collaboration. These areas include sequence generation,
sacubitril/valsartan in acute myocardial infarction, provid- allocation hiding, blinding, incomplete result data, selective
ing further evidence-based medical evidence for the clinical result reporting, and other sources of bias. The risk of bias in
application of sacubitril and valsartan in acute myocardial each study was classified as high, low, or unclear. We resolve
infarction. We have observed that for patients with heart any differences by consensus.
Journal of Healthcare Engineering 3

Table 1: Baseline characteristics of included studies.

Sex of Sex of
No. of No. of Intervention
Author Year Disease Age of exp. No. of con. exp. con. Intervention (exp.)
exp. con. (con.)
(M/total) (M/total)
Acute
Chi Chen 2021 myocardial 42 39 51.28 ± 6.27 51.3 ± 6.21 27/42 24/39 Sacubitril/valsartan Bisoprolol
infarction
Kieran Myocardial
2021 47 46 61.8 ± 10.6 59.7 ± 10.1 42/47 43/46 Sacubitril/valsartan Valsartan
F. Docherty infarction
ST-segment
Ahmed
elevation
Rwzq, MD. 2020 100 100 52 ± 9.2 57 ± 11.6 86/100 88/100 Sacubitril/valsartan Ramipril
myocardial
PHD.
infarction
Acute
Haiyan anterior wall
2020 68 69 59.13 ± 7.15 60.56 ± 7.62 52/68 54/69 Sacubitril/valsartan Enalapril
Wang myocardial
infarction
ST-elevation
Yi Zhang 2020 myocardial 79 77 60.3 ± 11.7 60 ± 10.9 59/79 55/77 Sacubitril/valsartan ACEI
infarction

2.4. Statistical Analyses. For the statistical analysis, we have 3.2. NT-proBNP, HF, and MACE. Data containing the value
used the Review Manager 5.3 software (The Cochrane of NT-proBNP were available from 4 studies. According to our
Collaboration; Copenhagen, Denmark). Continuous out- results, forest plots showed that the sacubitril/valsartan group
comes were expressed as standard mean differences (SMDs) had a 133% lower value of NT-proBNP to the control group
or mean differences (MDs) with 95% confidence intervals (MD � −1.33%, 95% CI: −1.54, −1.12, I2 � 96%, P < 0.00001,
(95% CIs). Dichotomous outcomes were expressed as risk Figure 3), and the difference was statistically significant.
ratio (OR) with 95% confidence intervals (95% CIs). Chi- Data containing heart failure data were available from 3
square-based Q-tests and I2 statistic were assessed to the studies. According to our results, forest plots showed that
heterogeneity among studies. If P values <0.10 or I2 >50%, the sacubitril/valsartan group had a 49% lower risk of heart
the random effects model was adopted to meta-analysis. failure to the control group (MD � 0.49, 95% CI: 0.27, 0.89,
Otherwise, the fixed effect model would be used. Sensitivity I2 � 0%, P � 0.02, Figure 3), and the difference was statis-
analysis was performed by omitting of any one study from tically significant.
the meta-analysis. Subgroup analysis for outcomes was also Data were available from 3 studies. The patients in ex-
performed to explore the influencing factors. perimental showed an obviously lower OR of MACE
(OR � 0.47, 95% CI: 0.27, 0.82, P � 0.007, Figure 3). The data
3. Results were statistically significant.

The baseline characteristics of the 5 eligible studies are given

in Table 1. 1012 relevant articles were identified by eligible 3.3. Publication Bias. We have conducted a publication bias
studies, characteristics literature search, and review of ref- test on 5 articles, and the test results prove that there is a
erence lists. After screening and eligibility assessment, we certain publication bias. For patients with heart failure after
included in the systematic review and meta-analysis a total acute myocardial infarction, early administration of sacu-
of 5 clinical trials involving the group of patients treated with bitril/valsartan can significantly reduce the incidence of
sacubitril/valsartan and the control treatment (Figure 1). heart rate, left ventricular ejection fraction, NT-proBNP,
and MACE. Our meta-analysis suggests that taking sacu-
bitril/valsartan is relatively safe and effective, especially if
3.1. LVEF and Heart Rate. Data about sacubitril/valsartan started early after acute myocardial infarction.
were available from 5 studies. Forest plots showed that the
sacubitril/valsartan group had a 299% higher value of 4. Discussion
sacubitril/valsartan to the control group (MD � 2.99%, 95%
CI: 2.01, 3.96, I2 � 78%, P < 0.00001, Figure 2), and the With the understanding of the concept of early myocardial
difference was statistically significant. reperfusion and the maturity of interventional techniques, the
Data about sacubitril/valsartan were available from 2 nosocomial mortality of AMI is significantly reduced, but
studies. Forest plots showed that the sacubitril/valsartan ARIC studies show that the incidence and mortality of HF after
group had a 531% lower value of sacubitril/valsartan to the myocardial infarction are still very high [19]. Even after suc-
control group (MD � −5.31%, 95% CI: −7.36, −3.26, cessful PCI, 30% of patients still experienced ventricular
I2 � 91%, P < 0.00001, Figure 2), and the difference was remodeling 6 months after surgery, increasing the risk of HF
statistically significant. and death after myocardial infarction. Therefore, prevention
4 Journal of Healthcare Engineering

2089 of records 25 of additional

identified through records identified
database through other
searching sources

467 of records after duplicates

removed

1647 of records
635 of records excluded
screened

1005 excluded
-Not English articles (n=19)
-Not related to myocardial infarction (n=231)
1012 of full-text -Not related to sacubitril/valsartan (n=144)
articles assessed -Not RCTs (n=611)
for eligibility

7 of studies included in
qualitative synthesis

5 of studies included in
quantitative synthesis
(meta-analysis)

Figure 1: Forest plots of flow diagram.

and reversal of ventricular remodeling to reduce the risk of and enhance the pumping function of the heart, so as to achieve
death or rehospitalization in patients with heart failure after MI normal blood supply to the heart [22]. RAAS can be divided
is the main therapeutic goal. The results of this retrospective into the cyclic RAAS pathway and organization RAAS pathway
analysis indicated that the effects of sacubitril/valsartan and [23]. The former affects the sodium metabolism and arterial
enalapril were similar, and the LVEF of the experimental group compliance to regulate arterial pressure and has short-term
was significantly higher than that of the control group after effects on pathophysiology [24]. The latter has long-term effects
treatment, indicating that sacubitril/valsartan effectively im- [25], converting angiotensin I to angiotensin II. Angiotensin II
proved left ventricular function, which was consistent with the secretion promotes the growth of cardiomyocytes and blood
results of the PARADIGM-HF trial [20]. Previous EVALU- vessels [26], increasing the amount of blood returning to the
ATE-HF study showed that [21] oral administration of sacu- heart. However, after long-term secretion, the sympathetic
bitril/valsartan significantly improved ventricular remodeling nervous system will continue to be activated, and aldosterone is
compared with oral administration and enalapril. Ventricular secreted in large quantities, accelerating the process of ven-
remodeling is an important pathophysiological basis of heart tricular remodeling, increasing myocardial contractility, ac-
failure after myocardial infarction. After the occurrence of celerating heart rate, water and sodium retention, and other
acute myocardial infarction, the human body automatically changes. Increased heart rate may also worsen heart failure and
activates the sympathetic nervous system and the RAAS system is emerging as a new therapeutic target [27]. Patients with acute
to increase blood volume, improve myocardial contractility, heart failure often have a higher basal heart rate than patients
Journal of Healthcare Engineering 5

Experimental Control Weight Mean Difference Mean Difference

Study or Subgroup Mean SD Total Mean SD Total (%) IV. Fixed. 95% Cl IV. Fixed. 95% Cl

Chi Chen 2021 56.1 3.47 42 51.3 3.68 39 39.3 4.80 [3.24, 6.36]
Haiyan Wang 2020 46.45 5.32 68 43.65 4.52 69 34.9 2.80 [1.15, 4.45]
Kieran F. Docherty 2021 36.9 6.6 46 39.1 7.3 46 11.8 -2.20 [-5.04, 0.64]
Yi Zhang 2020 49.8 11.8 79 47.2 11.3 77 7.3 2.60 [-1.03, 6.23]
Yi Zhang´ 2020 46.1 12.4 79 43.2 11.7 77 6.7 2.90 [-0.88, 6.68]

Total (95% Cl) 314 308 100.0 2.99 [2.01,3.96]

Heterogeneity: Chi2 = 18.06, df = 4 (P = 0.001); I2 = 78%
Test for overall effect: Z = 5 99 (P < 0.00001) –100 –50 0 50 100
Favours [experimental] Favours [control]

Experimental Control Weight Mean Difference Mean Difference

Study or Subgroup Mean SD Total Mean SD Total (%) IV. Fixed. 95% Cl IV. Fixed. 95% Cl

Chi Chen 2021 71.63 7.68 42 81.45 7.62 39 37.8 -9.82 [-13.15,-6.49]
Haiyan Wang 2020 74.73 8.77 68 77.3 6.56 69 62.2 -2.57 [-5.17,0.03]

Total(95%Cl) 110 108 100.0 -5.31 [-7.36,-3.26]

Heterogeneity: Chi2 = 11.31, df = 1 (P = 0.0008); I2 = 91%
–100 –50 0 50 100
Test for overall effect: Z = 5.08 (P < 0.00001)
Favours [experimental] Favours [control]

Figure 2: Forest plots of LVEF and heart rate.

Experimental Control Weight Std. Mean Difference Std. Mean Difference

Study or Subgroup Mean SD Total Mean SD Total (%) IV. Fixed. 95% Cl IV. Fixed. 95% Cl

Chi Chen 2021 410.3 38.88 42 510.52 38.62 39 12.5 -2.56 [-3.16, -1.97]
Haiyan Wang 2020 335.3 73.29 68 593.24 285.72 69 33.1 -1.23 [-1.59, -0.86]
Kieran F. Docherty 2021 168 18.97 46 235 21.32 46 11.0 -3.29 [-3.93, -2.66]
Yi Zhang 2020 1,760 537 79 2,079 615 77 43.3 -0.55 [-0.87, -0.23]

Total (95% Cl) 235 231 100.0 -1.33 [-1.54, -1.12]

Heterogeneity: Chi2 = 76.27, df = 3 (P < 0.00001); I2 = 96%
-4 -2 0 2 4
Test for overall effect: Z = 12.36 (P < 0.00001) Favours [experimental] Favours [control]

Experimental Control Weight Odds Ratio Odds Ratio

Study or Subgroup Events Total Events Total (%) M-H, Fixed, 95% Cl M-H, Fixed, 95% Cl

Chi Chen 2021 3 42 6 39 18.2 0.42 [0.10,1.82]

Haiyan Wang 2020 15 68 21 69 51.1 0.65 [0.30,1.40]
Yi Zhang 2020 3 79 10 77 30.7 0.26 [0.07,1.00]

Total (95% Cl) 189 185 100.0 0.49 [0.27,0.89]

Total events 12 37
Heterogeneity: Chi2 = 1.37, df = 2 (P = 0.51); l2 = 0%
0.01 0.1 1 10 100
Test for overall effect: Z = 2.35 (P = 0.02)
Favours [experimental] Favours [control]

Experimental Control Weight Odds Ratio Odds Ratio

Study or Subgroup Events Total Events Total (%) M-H, Fixed, 95% Cl M-H, Fixed, 95% Cl

Chi Chen 2021 4 42 10 39 24.5 0.31 [0.09, 1.07]

Haiyan Wang 2020 27 68 37 69 57.7 0.57 [0.29, 1.12]
Yi Zhang 2020 3 79 7 77 17.8 0.39 [0.10, 1.59]

Total (95% Cl) 189 185 100.0 0.47 [0.27, 0.82]

Total events 34 54
Heterogeneity: Chi2 = 0.82, df = 2 (P = 0.66); I2 = 0%
Test for overall effect: Z = 2.69 (P = 0.007) 0.01 0.1 1 10 100
Favours [experimental] Favours [control]

Figure 3: Forest plots of NT-proBNP, HF, and MACE.

with chronic heart failure [28]. Previous studies have shown heart rate decreases by more than HR 27 during hospitaliza-
that the incidence of all-cause death and readmission is sig- tion. At the same time, it is suggested that clinical stability and
nificantly reduced in patients with acute heart failure if their discharge are the key stages of heart rate control, and heart rate
6 Journal of Healthcare Engineering

should be closely monitored and controlled [29]. Although patients [40]. Our analysis showed that the incidence of
heart rate control in patients with acute heart failure can be MACE was lower in the observation group than in the
beneficial, rate control in clinical practice centers is unsatis- control group after treatment with sacubitril/valsartan.
factory. A European study showed that although >80% patients The limitations of this study are as follows: the overall
were treated with beta-blockers, only <25% of patients reached quality of the literature is not high, and the sample size is
the target dose, and <50% patients with acute heart failure small; due to the quality of the articles, some literatures did
reached the target heart rate (<70 beats/min) before discharge not specify specific random methods; some literatures did
[30], limits the benefit patients can get from controlling their not specify the specific use of Western medicine for con-
heart rate. The results of this analysis showed that the heart rate ventional treatment and only limited the drugs recom-
of the experimental group was significantly lower than that of mended by the guidelines; meanwhile, differences in
the control group. Therefore, sacubitril/valsartan can safely and subjects’ age and concomitant diseases may increase the
effectively reduce the heart rate of patients with acute clinical heterogeneity between studies; and high clinical
decompensated heart failure. costs of sacubitril/valsartan.
Second, the results of this retrospective analysis showed Therefore, we demonstrated that sacubitril/valsartan
that the NT-proBNP decreased significantly after the sodium tablets can inhibit ventricular remodeling after acute
treatment of sacubitril/valsartan, and the experimental myocardial infarction, improve cardiac function, reduce the
group was superior to the control group, suggesting that incidence of adverse cardiovascular events, the rate of
sacubitril/valsartan were safe and effective in the treatment rehospitalization and mortality after myocardial infarction,
of AMI with cardiac insufficiency. Coincidentally, it is and improve disease prognosis without significant adverse
consistent with the results of PIONEER-HF experimental reactions. However, due to the limitations of the quality and
study [31,32]. BNP and NT-proBNP are neuroendocrine quantity of the included literature and the risk of bias, its
hormones secreted by the heart, which have been proved to efficacy will be overevaluated, which needs to be further
be important indicators for clinical diagnosis, treatment, and confirmed by big data and high-quality prospective ran-
prognosis of patients with heart failure [33,34]. BNP was first domized controlled studies to provide higher evidence-
isolated from pigs and subsequently found to be mainly based medical evidence.
synthesized in ventricles. Its concentration can change with
ventricular wall tension and has a negative feedback regu- 5. Conclusion and Future Directives
lating effect on ventricular filling pressure, so it has become
an important biomarker. ProBNP is a precursor of BNP, an To assess the effect of sacubitril/valsartan on heart failure
amino acid polypeptide, found in heart muscle cells. The after acute myocardial infarction, we conducted a systematic
gene transcription of BNP is induced by stretching the review of the literature and a meta-analysis of existing
myocardial wall, such as ventricular remodeling, resulting in randomized clinical trials. Meta-analysis of randomized
the lysis of proBNP into two fragments, namely, NT- controlled trails is used where data are collected from
proBNP and active BNP fragments. Active BNP can cause a PubMed, the Cochrane library, Embase, and Web of Science.
series of responses to ventricular dilation, such as natriuretic, Data about sacubitril/valsartan were available from 5 studies.
diuretic, vasodilator, inhibition of renin, and aldosterone Forest plots showed that the sacubitril/valsartan group had a
secretion [35]. At the same time of the occurrence of AMI, 299% higher value of sacubitril/valsartan to the control
the BNP synthesis gene of the living cells around the infarct group (MD � 2.99%, 95% CI: 2.01, 3.96, I2 � 78%,
area and the cells in the noninfarct area rapidly transcribed P < 0.00001, Figure 2), and the difference was statistically
mRNA, and the increase of ventricular volume load further significant. Forest plots showed that the sacubitril/valsartan
induced the overexpression of mRNA, and BNP was rapidly group had a 531% lower value of LVEF to the control group
synthesized and released into blood. BNP has a half-life of (MD � −5.31%, 95% CI: −7.36, −3.26, I2 � 91%, P < 0.00001,
about 20 minutes, while NT-proBNP has a half-life of about Figure 2), and the difference was statistically significant.
60–120 minutes, which is more stable than BNP [36]. Forest plots showed that the sacubitril/valsartan group had a
Therefore, NT-proBNP plays an important role in evaluating 133% lower value of NT-proBNP to the control group
the size of myocardial infarction, the therapeutic effect of (MD � −1.33%, 95% CI: −1.54, −1.12, I2 � 96%, P < 0.00001,
myocardial cell reperfusion, and the prediction of late Figure 3). Forest plots showed that the sacubitril/valsartan
myocardial remodeling [18]. Large-scale clinical studies group had a 49% lower risk of heart failure to the control
[37–39] showed that in STEMI and NSTEMI patients, group (MD � 0.49, 95% CI: 0.27, 0.89, I2 � 0%, P � 0.02,
plasma levels of BNP and NT-proBNP at admission were Figure 3). The patients in experimental showed an obviously
positively correlated with the incidence of subsequent ad- lower OR of MACE (OR � 0.47, 95% CI: 0.27, 0.82,
verse events such as death from all causes, recurrent P � 0.007, Figure 3). The data were statistically significant.
myocardial infarction, rehospitalization, and prolonged We have observed that for patients with heart failure after
hospital stay. MACE in patients with acute myocardial in- acute myocardial infarction, early administration of sacu-
farction after PCI will seriously threaten their life, health, bitril/valsartan can significantly reduce the incidence of
and quality of life, and accurate prediction of the risk of heart rate, left ventricular ejection fraction, NT-proBNP,
MACE after PCI is conducive to early adoption of corre- and MACE. Our meta-analysis suggests that taking sacu-
sponding prevention and control measures, so as to reduce bitril/valsartan is relatively safe and effective, especially if
the occurrence of MACE and ensure good outcomes of started early after acute myocardial infarction.
Journal of Healthcare Engineering 7

Data Availability Myocardial Infarction Trial (VALIANT).” Journal of the

American College of Cardiology, vol. 47, no. 4, 2006.
The datasets used during the current study are available from [13] J. J. V. McMurray, M. Packer, and A. S. Desai, “Angio-
the corresponding author upon request. tensin–neprilysin inhibition versus enalapril in heart failure,”
New England Journal of Medicine, vol. 371, pp. 993–1004,
Conflicts of Interest 2014.
[14] Toru, K. Nakamura, D. Miura et al., “Effect of LCZ696, a dual
The authors declare that they have no conflicts of interest. angiotensin receptor neprilysin inhibitor, on isoproterenol-
induced cardiac hypertrophy, fibrosis, and hemodynamic
change in rats,” . Cardiology journal, vol. 26, no. 5, 2019.
References [15] Schoenfeld, T. West, P. B. Verghese et al., “The effect of
[1] F. Arslan, L. Bongartz, J. M. Berg et al., “ESC guidelines for the angiotensin receptor neprilysin inhibitor, sacubitril/valsartan,
management of acute myocardial infarction in patients pre- on central nervous system amyloid-β concentrations and
senting with ST-segment elevation:comments from the Dutch clearance in the cynomolgus monkey,” Toxicology and Applied
ACS working group,” Netherlands Heart Journal Monthly Pharmacology, vol. 323, pp. 53–65, 2017.
Journal of the Netherlands Society of Cardiology&the Nethe- [16] H. Nakagawa, O. Heike, O. Nikolaev Viacheslav et al., “Atrial
rlands Heart Foundation, vol. 26, pp. 1–5, 2017. natriuretic peptide locally counteracts the deleterious effects
[2] Y. Huo, “Promoting chest pain center accreditation is an of cardiomyocyte mineralocorticoid receptor activation,” .
essential way to improve the management of acute myocardial Circulation. Heart failure, vol. 7, no. 5, 2014.
infarction in China,” . Zhonghua xin xue guan bing za zhi, [17] Ponikowski, A. A. Voors, S. D. Anker et al., “ESC guidelines
vol. 42, no. 8, pp. 637–8, 2014. for the diagnosis and treatment of acute and chronic heart
[3] Marek, K.-W. Magdalena, W. Maciej et al., “Left ventricular failure,” Revista Española de Cardiologı́a, vol. 69, no. 12, 2016.
reverse remodeling in patients with anterior wall ST-segment [18] F. Docherty Kieran, V. Muthiah, and D. Solomon Scott,
elevation acute myocardial infarction treated with primary “McMurray john J V. Sacubitril/valsartan: neprilysin inhi-
percutaneous coronary intervention.” Postepy w kardiologii bition 5 Years after PARADIGM-HF,” JACC. Heart failure,
interwencyjnej � Advances in interventional cardiology, vol. 14, vol. 8, no. 10, 2020.
no. 4, pp. 373–382, 2018. [19] T. Qureshi, Z.-M. Zhang, P. P. Chang et al., “Silent myocardial
[4] P. van der Bijl, R. Abou, G. Laurien et al., “Left ventricular infarction and long-term risk of heart failure,” Journal of the
remodelling after ST-segment elevation myocardial infarc- American College of Cardiology, vol. 71, no. 1, 2018.
tion: sex differences and prognosis,” . ESC heart failure, vol. 7, [20] J. V. McMurray John, P. Milton, S. Desai Akshay et al., “Dual
no. 2, 2020. angiotensin receptor and neprilysin inhibition as an alter-
[5] Greco, S. Rosato, P. D’Errigo, G. F Mureddu, E. Lacorte, and native to angiotensin-converting enzyme inhibition in pa-
F. Seccareccia, “Trends in mortality and heart failure after tients with chronic systolic heart failure: rationale for and
acute myocardial infarction in Italy from 2001 to 2011,” In- design of the Prospective comparison of ARNI with ACEI to
ternational Journal of Cardiology, vol. 1, pp. 115–121, 2015. Determine Impact on Global Mortality and morbidity in
[6] A. Pfeffer Marc, E. Braunwald, A. Moyé lemuel et al., “Effect of Heart Failure trial (PARADIGM-HF),” . European journal of
captopril on mortality and morbidity in patients with left heart failure, vol. 15, no. 9, 2013.
ventricular dysfunction after myocardial infarction:results of [21] S. Desai, D. Scott, A. M. S. Solomon et al., “Effects of sacu-
the survival and ventricular enlargement trial,” New England bitril-valsartan compared with enalapril on arterial hemo-
Journal of Medicine, vol. 327, no. 10, 1992. dynamics, cardiac remodeling, and quality of life in patients
[7] H. J. Dargie, “Effect of carvedilol on outcome after myocardial
with heart failure and reduced ejection fraction,” Journal of
infarction in patients with left-ventricular dysfunction: the
Cardiac Failure, vol. 25, no. 11, 2019.
CAPRICORN randomised trial,” The Lancet, vol. 357, 2001.
[22] M. Schmidt, E. Mansfield Kathryn, B. Krishnan et al., “Ad-
[8] Zannad, M. Gheorghiade, K. Henry, T.-C. Chu, R. Patni, and
herence to guidelines for creatinine and potassium moni-
B. Pitt, “The effect of eplerenone on all-cause mortality and
toring and discontinuation following renin-angiotensin
heart failure hospitalization in the eplerenone post-acute
myocardial infarction heart failure efficacy and survival study system blockade: a UK general practice-based cohort study,”
(EPHESUS),” Journal of Cardiac Failure, vol. 10, no. 4, 2004. BMJ open, vol. 7, no. 1, 2017.
[9] The Acute Infarction Ramipril Efficacy (AIRE) Study Inves- [23] K. Park, C. Gaze David, O. Collinson Paul, and S. Marber
tigators, “Effect of ramipril on mortality and morbidity of Michael, “Cardiac troponins: from myocardial infarction to
survivors of acute myocardial infarction with clinical evidence chronic disease,” Cardiovascular research, vol. 113, no. 14,
of heart failure,” Clinical Trail, vol. 342, 1993. 2017.
[10] L. Køber, C. Torp-Pedersen, J. E. Carlsen et al., “A clinical trial [24] Liao, K. Chen, X. Dong et al., “Berberine inhibits cardiac
of the angiotensin-converting-enzyme inhibitor trandolapril remodeling of heart failure after myocardialinfarction by
in patients with left ventricular dysfunction after myocardial reducing myocardial cell apoptosis in rats,” Experimental and
infarction. Trandolapril Cardiac Evaluation (TRACE) study Therapeutic Medicine, vol. 16, no. 3, 2018.
group,” The New England journal of medicine, vol. 333, no. 25, [25] “ats,” Frontiers in Physiology, vol. 9, p. 1242, 2018.
1995. [26] R. Zullo, S. Sadia, M. S. Yoojin Lee et al., “Secondary pre-
[11] A. P. Robin, P. B. M. Weir, C. J. Petrie et al., “Left ventricular vention medication use after myocardial infarction in U.S.
remodeling after acute myocardial infarction: does eplerenone Nursing home residents,” Journal of the American Geriatrics
have an effect?” American Heart Journal, vol. 157, no. 6, 2009. Society, vol. 65, no. 11, 2017.
[12] S. Scott, P. Karen, S. Reed et al., “The effect of valsartan, [27] Patrizio, A. Arnaud, M. Julien, F. Giovanni, and A. Piérard
captopril, or both on atherosclerotic events after acute Luc, “Elevated heart rate at 24-36h after admission and in-
myocardial infarction: an analysis of the Valsartan in Acute hospital mortality in acute in non-arrhythmic heart failure,”
8 Journal of Healthcare Engineering

International Journal of Cardiology, vol. 182, pp. 426–430,

2015.
[28] Luigi, S. Michele, M. Marco et al., “Multicenter prospective
observational study on acute and chronic heart failure: one-
year follow-up results of IN-HF (Italian network on heart
failure) outcome registry,” Circulation. Heart Failure, vol. 6,
no. 3, 2013.
[29] Takahama, H. Yokoyama, A. Kada et al., “The extent of heart
rate reduction during hospitalization using beta-blockers, not
the achieved heart rate itself at discharge, predicts the clinical
outcome in patients with acute heart failure syndromes,”
Journal of Cardiology, vol. 61, no. 1, 2013.
[30] Farmakis, J. Parissis, A. Karavidas et al., “In-hospital man-
agement of acute heart failure: practical recommendations
and future perspectives,” International Journal of Cardiology,
vol. 201, pp. 231–236, 2015.
[31] J. Velazquez Eric, A. Morrow David, D. DeVore Adam et al.,
“Angiotensin-neprilysin inhibition in acute decompensated
heart failure.” New England Journal of Medicine, vol. 380,
no. 6, 2019.
[32] A. Morrow, E. J. Velazquez, A. D. DeVore et al., “Clinical
outcomes in patients with acute decompensated heart failure
randomly assigned to sacubitril/valsartan or enalapril in the
PIONEER-HF trial,” Circulation, vol. 139, no. 19, 2019.
[33] S. L. Chow, A. S. Maisel, I. Anand et al., “Role of biomarkers
for the prevention, assessment, and management of heart
failure: a scientific statement from the American heart as-
sociation,” Circulation, vol. 135, no. 22, 2017.
[34] R. Troughton, G. Michael Felker, and J. L. Januzzi, “Natri-
uretic peptide-guided heart failure management,” European
Heart Journal, vol. 35, no. 1, 2014.
[35] -Na Kim and J. L. Januzzi, “Natriuretic peptide testing in heart
failure,” Circulation, vol. 123, no. 18, 2011.
[36] P. Jin Joo, D.-J. Choi, Y. Chang-Hwan et al., “Prognostic value
of C-reactive protein as an inflammatory and N-terminal
probrain natriuretic peptide as a neurohumoral marker in
acute heart failure (from the Korean heart failure registry),”
The American Journal of Cardiology, vol. 113, no. 3, pp. 511–1,
2014.
[37] A. Morrow David, A. de Lemos James, S. Sabatine Marc et al.,
“Evaluation of B-type natriuretic peptide for risk assessment
in unstable angina/non-ST-elevation myocardial infarction:
B-type natriuretic peptide and prognosis in TACTICS-TIMI
18.” Journal of the American College of Cardiology, vol. 41,
no. 8, pp. 533–541, 2003.
[38] R. E. Manenti Euler, C. Bodanese Luiz, A. Camey Suzi, and
A. Polanczyk Carisi, “Prognostic value of serum biomarkers in
association with TIMI risk score for acute coronary syn-
dromes.” Clinical Cardiology, vol. 29, no. 9, 2006.
[39] K. James, B. Lindahl, and A. Siegbahn, “N-terminal pro-brain
natriuretic peptide and other risk markers for the separate
prediction of mortality and subsequent myocardial infarction
in patients with unstable coronary artery disease: a global
utilization of strategies to open occluded arteries (GUSTO)-
IV substudy circulation,” ACC Current Journal Review,
vol. 12, no. 6, 2003.
[40] B. Yuli Setianto, A. Budi Hartopo, I. Sukmasari, and
I. Puspitawati, “On-admission high endothelin-1 level inde-
pendently predicts in-hospital adverse cardiac events fol-
lowing ST-elevation acute myocardial infarction,”
International Journal of Cardiology, vol. 220, 2016.