3.1. Search results and basic information of patients
A total of 75 records were identified in the initial retrieval. After screening, a total of 7 studies[10–16] with 964 patients were included for the meta-analysis. The process of study inclusion was shown in Fig. 1. At the same time, researchers summarized basic information of patients from extracted data, which was illustrated in Table 1.
3.2. Results of quality evaluation
Most of the researchers[10–14] used randomization in their trials, including random draws, the table of random digits, random permuted blocks, and a computer-generated list. Only two studies[15, 16] conducted allocation concealment method. In addition, Zhang[16] notified that the clinical trial was not double-blind because of the limitation of local conditions. Wang[15] and Dong[11] reported the loss of follow-up, but its influence on experimental outcomes was unclear. No evidence for selective reporting was detected. Other bias of all studies remained unclear. The outcomes of quality evaluation were summarized in Fig. 2 and Fig. 3.
3.3. Meta-analysis of rehospitalization for HF
The rehospitalization for HF after STEMI was analyzed in a total of 5 studies with 784 patients. The outcomes of heterogeneity test showed that P = 0.45 and I2 = 0%, which indicated that there was no significant heterogeneity. Therefore, fixed-effects model was adopted for combined analysis. The results of combined analysis were RR = 0.45 (95% CI: 0.35 to 0.66). Meanwhile, the results of significance test were Z = 4.55 and P < 0.00001, indicating that there were significant statistical differences between Sac/Val group and ACEI/ARB group. The outcomes showed, compared with ACEI/ARB group, Sac/Val was able to significantly reduce rehospitalization for HF in patients with STEMI. More detailed data were shown in Fig. 4 (A).
3.4. Meta-analysis of LVEF
The LVEF after STEMI was analyzed in a total of 7 studies with 964 patients. The outcomes of heterogeneity test showed that P = 0.11 and I2 = 42%, which indicated there was no significant heterogeneity. Therefore, fixed-effects model was adopted for combined analysis. The results of combined analysis were MD = 3.44 (95% CI: 2.66 to 4.22). Meanwhile, the results of significance test were Z = 8.66 and P < 0.00001, indicating that there were significant statistical differences between Sac/Val group and ACEI/ARB group. The outcomes showed, compared with ACEI/ARB group, patients’ cardiac functions were better in Sac/Val group. More detailed data were shown in Fig. 4 (B).
3.5. Meta-analysis of MACEs
The MACEs after STEMI were analyzed in a total of 7 studies with 964 patients. The outcomes of heterogeneity test showed that P = 0.10 and I2 = 44%, which indicated there was no significant heterogeneity. Therefore, fixed-effects model was adopted for combined analysis. The results of combined analysis were RR = 0.50 (95% CI: 0.40 to 0.62). Meanwhile, the results of significance test were Z = 6.06 and P < 0.00001, indicating that there were significant statistical differences between Sac/Val group and ACEI/ARB group. The outcomes showed patients in Sac/Val group had smaller MACEs incidence than those in ACEI/ARB group. More detailed data were shown in Fig. 4 (C).
3.6. Meta-analysis of NT-proBNP concentration at 24 weeks
The NT-proBNP concentration at 24 weeks after STEMI was analyzed in a total of 4 studies with 377 patients. The outcomes of heterogeneity test showed P < 0.0001 and I2 = 91%, which indicated there was significant heterogeneity. Therefore, random-effects model was adopted for combined analysis. The results of combined analysis were MD=-155.55 (95% CI: -226.35 to -84.75). Meanwhile, the results of significance test were Z = 4.31 and P < 0.0001, indicating that there were significant statistical differences between Sac/Val group and ACEI/ARB group. The outcomes showed that Sac/Val was superior to ACEI/ARB in decreasing the concentration of NT-proBNP, indicating that Sac/Val could effectively relieve patients' HF. More detailed data were shown in Fig. 4 (D).
3.7. Meta-analysis of adverse side effects of medication
The adverse side effects of medication, including hypotension, hyperkalemia, cough, and worsening renal function, were analyzed in a total of 4 studies with 628 patients. The outcomes of adverse side effects were summarized in this paragraph.
In terms of hypotension, the outcomes of heterogeneity test showed P = 0.62 and I2 = 0%, which indicated there was no significant heterogeneity. Therefore, fixed-effects model was adopted for combined analysis. The results of combined analysis were RR = 1.81 (95% CI: 1.09 to 3.02). Meanwhile, the results of significance test were Z = 2.29 and P = 0.02, indicating that there were significant statistical differences between Sac/Val group and ACEI/ARB group. The outcomes showed that Sac/Val group might face a higher risk of drug-induced hypotension than ACEI/ARB group. More detailed data were shown in Fig. 4 (E).
In terms of hyperkalemia, the outcomes of heterogeneity test showed P = 0.55 and I2 = 0%, which indicated there was no significant heterogeneity. Therefore, fixed-effects model was adopted for combined analysis. The results of combined analysis were RR = 0.58 (95% CI: 0.17 to 1.93). Meanwhile, the results of significance test were Z = 0.89 and P = 0.37, indicating that there were no significant statistical differences between Sac/Val group and ACEI/ARB group. The outcomes showed, in the aspect of drug-induced hyperkalemia, Sac/Val was unable to gain statistical advantages over ACEI/ARB. More detailed data were shown in Fig. 4 (F).
In terms of cough, the outcomes of heterogeneity test showed P = 0.55 and I2 = 0%, which indicated there was no significant heterogeneity. Therefore, fixed-effects model was adopted for combined analysis. The results of combined analysis were RR = 0.84 (95% CI: 0.26 to 2.72). Meanwhile, the results of significance test were Z = 0.29 and P = 0.77, indicating that there were no significant statistical differences between Sac/Val group and ACEI/ARB group. The outcomes showed, in the aspect of drug-induced cough, Sac/Val was unable to gain statistical advantages over ACEI/ARB. More detailed data were shown in Fig. 4 (G).
In terms of worsening renal function, the outcomes of heterogeneity test showed P = 0.88 and I2 = 0%, which indicated there was no significant heterogeneity. Therefore, fixed-effects model was adopted for combined analysis. The results of combined analysis were RR = 0.55 (95% CI: 0.23 to 1.33). Meanwhile, the results of significance test were Z = 1.34 and P = 0.18, indicating that there were no significant statistical differences between Sac/Val group and ACEI/ARB group. The outcomes showed, in the aspect of drug-induced worsening renal function, Sac/Val was unable to gain statistical advantages over ACEI/ARB. More detailed data were shown in Fig. 4 (H).
3.8. Sensitivity analysis and evaluation of publication bias
In order to further explore the heterogeneity of included studies, sensitivity analysis was performed with StataMP 14.0 software. No study was identified as a source of heterogeneity, proving that the heterogeneity detected in the meta-analysis of NT-proBNP concentration at 24 weeks was not caused by a certain study. Considering the data of NT-proBNP concentration were collected through blood samples, researchers hypothesized that the differences in sampling and measuring methods between studies might be the explanation for the heterogeneity detected in the meta-analysis of NT-proBNP concentration at 24 weeks. More details were shown in Fig. 5 (A)-(H).
According to the Cochrane Handbook[17], the test of funnel plot should be used only when there were at least 10 studies included for meta-analysis. Yet in this analysis, only 7 studies were included. Thus, the test of funnel plot was not adopted. Instead, researchers performed more powerful Egger test to assess the publication bias. Unfortunately, due to the lack of data, the Egger tests of hyperkalemia and worsening renal function failed to conduct, leading to the publication bias of these two outcomes being unknown.
In the Egger test of publication bias, the P values and 95% CI of rehospitalization for HF, LVEF, MACEs, NT-proBNP concentration at 24 weeks, hypotension, and cough were P = 0.227 (95% CI: -2.42 to 0.86), P = 0.022 (95% CI: 2.11 to 17.01), P = 0.022 (95% CI: -2.08 to -0.25), P = 0.184 (95% CI: -25.85 to 15.04), P = 0.346 (95% CI: -15.07 to 19.59), and P = 0.765 (95% CI: -74.62 to 79.30). The outcomes of Egger test indicated that the meta-analysis of LVEF and MACEs might be influenced by publication bias. The details were shown in Fig. 6 (A)-(F).