Dr Zhixing Fan, Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, 181 Yilin Road, Yichang, Hubei 443000, P.R. China
To evaluate the effects and safety of sacubitril/valsartan in patients with acute myocardial infarction (AMI), a total of four databases, including PubMed, Cochrane Library, Embase and Web of Science, and the
Acute myocardial infarction (AMI) is a major cause of disability and mortality worldwide (
In recent years, although the application of conventional heart failure treatment following myocardial infarction has reduced the mortality of patients to a certain extent, the incidence of cardiac insufficiency following AMI remains high (
The inclusion criteria were defined according to the Population, Intervention, Comparison, Outcome and Study design tool (
The exclusion criteria (in terms of the publications) were as follows: Republished studies, studies with no available data, studies in which the full text was not available, and studies written in a language other than English.
PubMed (
Two researchers (SSL and BY) independently searched and screened the literature according to the inclusion and exclusion criteria. Any potential disagreements were resolved by discussion until either a consensus was reached, or a third author (BW or ZXF) was consulted. The extracted information included the basic information of the study in question and the original research data of the outcomes. The data that could not be directly extracted were obtained either by data transformation or by contacting the authors.
The Cochrane collaboration bias risk assessment tool recommended by the Cochrane handbook (
Statistical analysis of the data was performed using Review Manager 5.3 (
A total of 684 articles were obtained by searching the databases, and a total of 386 articles were retrieved after removing duplicates. By reading the titles and abstracts, 375 articles were initially excluded according to the inclusion and exclusion criteria (189 were found not to be clinical trials, 125 were not intervention studies, 34 were not dealing with patients with AMI, and 27 articles were not concerned with sacubitril and valsartan interventions). A total of 11 articles were subsequently investigated, and seven of them were excluded upon reading their full text. For the seven excluded articles, three were not RCTs, three articles had unavailable outcomes and one was without available data. Ultimately, four studies were included in the meta-analysis (
A total of four studies were included. The basic information of the included studies is shown in
Quality assessment of the included studies is shown in
An overall analysis for the primary outcomes is presented in
Following AMI, disordered ventricular muscle contraction, activation of the RAAS and ventricular remodeling may lead to cardiac insufficiency, or even pump failure (
As the first dual-effect compound preparation of an enkephalinase inhibitor and ARB, sacubitril and valsartan have been reported to exert a dual role in neuroendocrine system activity (
Recently published clinical studies have revealed that early application of sacubitril/valsartan following emergency PCI in patients with AMI can effectively improve left ventricular remodeling, reduce the occurrence of cardiac insufficiency and adverse cardiovascular events, and reduce the rehospitalization rate (
The present study has a number of limitations. First, the number of included studies was only four and the study sample size was small. Hence, although there were no significant differences in hypotension between the two groups, it must be emphasized that attention should be paid to changes in blood pressure considering that this is the most common side effect of sacubitril/valsartan. Furthermore, certain studies did not provide blinding of participants. In addition, certain articles did not specify what the specific medications for the conventional/control treatment were. The heterogeneity in the meta-analysis of the primary outcome, adverse events, was significant. The differences in study design, including differences in patient age, severity of MI, comorbidities, the dose of sacubitril/valsartan and the specific medications for conventional treatment, may have resulted in heterogeneity in the meta-analysis of adverse events. However, the type of adverse event may be slightly different, which may cause the heterogeneity. Rezq
In conclusion, the present meta-analysis revealed that sacubitril/valsartan may effectively reduce the incidence of MACCEs, readmission and AHF in patients with AMI following revascularization without any obvious adverse events. However, given the limitations in the quality and quantity of the included articles and the risk of bias, these findings need to be further confirmed by big-data and high-quality prospective randomized controlled studies in order to provide corroborating evidence.
The authors would like to thank Dr Chaojun Yang, Dr Jun Yang and Dr Jian Yang (Department of Cardiology, Three Gorges University, Yichang, China) for editing the English text of a draft of this manuscript and for the registration in PROSPERO.
The present meta-analysis was performed, and has been reported, according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (CRD42021269433,
BY and ZXF conceived and designed the current study, defined the content of the research, conducted literature search, performed statistical analysis and prepared and edited the manuscript. SSL is the guarantor of study integrity, designed the current study, defined the content of the research and reviewed the manuscript. BW conducted the literature search, acquired data and performed statistical analysis. BY and ZXF confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.
Not applicable.
Not applicable.
The authors declare that they have no competing interests.
Flow diagram showing the study selection protocol. RCT, randomized controlled trial.
Quality evaluation of the included studies. (A) Risk of bias graph and (B) risk of bias summary.
Forest plots of (A) MACCEs, (B) readmission, (C) adverse events, (D) incidence of AHFs and (E) hypotension. MACCEs, major adverse cardiovascular and cerebrovascular events; AHF, acute heart failure; 95% CI, 95% confidence interval.
Forest plots of (A) NT-proBNP, (B) LVEF and (C) sST2. NT-proBNP, N-terminal pro B-type natriuretic peptide; LVEF, left ventricular ejection fraction; sST2, soluble suppression of tumorigenesis-2; 95% CI, 95% confidence interval.
Sensitivity analysis of LVEF. The S-axis presents the odds ratio with the respective study omitted. LVEF, left ventricular ejection fraction; CI, confidence interval.
Characteristics of the included studies.
Sex, M/F | Mean age ± SD, years | Intervention | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
First author, year | Country | Research | Characteristics | Sample size, T/C | T | C | T | C | Type of AMI | AMI treatment | T | C | Dosage of Sal/Val | Time between AMI and intervention | Follow-up, months | (Refs.) |
Zhang, |
China | Prospective single-center RCT | Not double- blinded | 79/77 | 59/20 | 55/22 | 60.30±11.70 | 60.00±10.90 | All STEMI | All PCI | Sal/Val + RBT | Perindopril + RBT | According to patient condition | Early administration of Sal/Val within 24 h after PCI | 6 | ( |
Wang, |
China | Prospective single-center RCT | Blinded | 68/69 | 52/16 | 54/15 | 59.13±7.15 | 60.56±7.62 | All STEMI | All PCI | Sal/Val + RBT | Enalapril + RBT | 24/26 or 49/51 mg bid and then up titration | When hemodynamic stabilization reached after PCI | 6 | ( |
Rezq, |
Egypt | Prospective multicenter RCT | Double- blinded | 100/100 | 86/14 | 88/12 | 52.00±9.20 | 57.00±11.60 | All STEMI | All PCI | Sal/Val + RBT | Ramipril + RBT | 50 or 100 mg bid | After PCI | 6 | ( |
Docherty, |
UK | Prospective multicenter RCT | Double- blinded | 47/46 | 42/5 | 43/3 | 61.80±10.60 | 57.00±11.60 | 90 STEMI and 30 NSTEMI | 86 PCI, one thrombolysis and three CABG | Sal/Val + RBT | Valsartan + RBT | 24/26, 49/51 and 97/103 mg bid | >3 months after PCI | 12 | ( |
RCT, randomized controlled trial; T, experimental group; C, control group; AMI, acute myocardial infarction; STEMI, ST segment elevation myocardial infarction; NSTEMI, non-ST segment elevation myocardial infarction; PCI, percutaneous transluminal coronary intervention; CABG, coronary artery bypass grafting; Sal, sacubitril; Val, valsartan; RBT, routine basic treatment; bid, two times per day; M, male; F, female.