Acute myocardial infarction (AMI) is a significant global health issue characterized by high morbidity and mortality rates, imposing substantial economic and medical burdens (Mensah et al., 2023). AMI is usually caused by coronary artery disease, and research has found that AMI can be associated with cerebrovascular diseases, making clinical diagnosis and treatment more difficult due to comorbidities of the heart and brain (Suzuki et al., 2023). Over the past decade, the management of AMI in China has made some progress. However, the China Cardiovascular Health and Disease Report 2023 Summary revealed an increase in AMI mortality in China from 2002 to 2021 (National Center Cardiovascular Diseases, 2024). With the active promotion of secondary prevention measures for coronary heart disease and early reperfusion therapy for AMI, the mortality rate of AMI patients has decreased (Roger et al., 2010). There are still several unresolved issues after reperfusion, including decreased myocardial contractility, ventricular arrhythmia, and no-reflow phenomenon (Thiele et al., 2017). These complications have a significant impact on the prognosis of patients (Heusch and Gersh, 2017). Therefore, exploring additional effective treatment methods remains essential.

Traditional Chinese medicine (TCM) can play a unique role in improving the clinical prognosis of AMI. Research has found that for STEMI patients, on the basis of standardized biomedicine treatment (including reperfusion therapy and optimal drug therapy), Tongxinluo can significantly improve clinical prognosis, and reduce the risk of major adverse cardiovascular and cerebrovascular events at 30°days and 1°year (Yang et al., 2023). Consequently, there is a growing interest among Chinese medical professionals in exploring therapeutic approaches from TCM to help reduce AMI mortality. This research direction aligns with the principles exemplified by Professor Tu Youyou, the Nobel Prize laureate who successfully extracted artemisinin from Artemisia annua, thereby revolutionizing malaria treatment.

One such intervention gaining attention is the use of traditional Chinese medicine injections for tonifying qi (TCMi-TQs), which possess comparable effects of regulating energy metabolism (Li et al., 2023; Wang et al., 2022; Wang A. et al., 2024; Yang et al., 2022). TCMi-TQs have shown promise in reducing mortality and the incidence of re-infarction among AMI patients (Jia et al., 2023; Lu et al., 2018). To obtain high-quality evidence regarding the safety and efficacy of TCMi-TQs in AMI, this study initiated a search for TCMi-TQs used in the treatment of AMI. The search yielded four TCMi-TQs: Shengmai injection (SGMI), Shenmai injection (SMI), Shenfu injection (SFI), and Astragalus injection (AI). Research has demonstrated that these four TCMi-TQs and their main active metabolites play a significant role in modulating myocardial energy metabolism in patients with myocardial ischemia. SGMI increases the number of myocardial cell mitochondria and scavenges oxygen-free radicals (Lu et al., 2005). SMI enhances myocardial microcirculation parameters (Yang and Wang, 2021), while SFI mitigates mitochondrial oxidative stress (Lu and Xiang, 2023). The primary active compound of AI, astragaloside IV, regulates myocardial cell oxidative stress and enhances mitochondrial function (Guan et al., 2023). Detailed information on these four TCMi-TQs is provided in Supplementary Tables S1–S4. The objective of this study is to systematically collect and analyze the data from these four randomized controlled trials (RCTs) investigating TCMi-TQs in the treatment of AMI, with the aim of evaluating its efficacy and safety for AMI patients presenting with relevant indications based on the current evidence. This study has the potential to bridge the gap between TCMi-TQs and modern medicine for AMI treatment and open up avenues for integrative care models for AMI patients.

The systematic review has been registered in the PROSPERO platform for prospective registration with the registration number CRD42024573818. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (Moher et al., 2015; Page et al., 2021) were employed to conduct our network meta-analysis, as seen in Supplementary Material. To ensure accurate reporting of four TCMIs in this analysis, we adhered to the guidelines established in the consensus statement on the Phytochemical Characterization of Medicinal Plant extract (ConPhyMP) (Supplementary Tables S1–S4) (Heinrich et al., 2022).

In China, the integration of TCM and biomedicine is increasingly becoming an anticipated model of medical development, as it contributes to addressing clinical issues more effectively. Taking AMI as an example, despite the rapid development of modern medical techniques, including PCI, in China, a turning point in the reduction of AMI mortality has not yet been observed (Tsao et al., 2022; GBD 2013 Mortality and Causes of Death Collaborators, 2015). Early intervention and diagnosis of diseases can reduce the incidence rate of AMI, but these areas need further research (Wang et al., 2024b; Wang et al., 2024c; Jaiswal et al., 2023). The standardized application of TCM may serve as a valuable approach to addressing this clinical issue. However, the process of integrating traditional and modern medicine requires support from high-quality evidence-based research. Our study contributes precisely to this by conducting relevant work.

Traditional Chinese Medicine injection (TCMi) refers to a sterile preparation extracted and purified from TCM, which can be in the form of a solution, emulsion, lyophilized powder, or concentrated solution (Zhang et al., 2021; Chen et al., 2022). It is known for its high bioavailability and precise therapeutic effects and has been widely used in China particularly in the treatment of AMI.

It is important to mention a concept in TCM known as “tong zheng yi bing” or “different diseases with the same pattern.” Specifically, even if it is not AMI, the same qi deficiency syndrome can be treated with medications that have the function of tonifying qi. Therefore, the use of TCMi may present issues with inappropriate indications. The TCMi selected in this study were those that have the function of tonifying qi. We identified four such TCMi through our search.

In Chinese medicine theory, qi is considered one of the fundamental substances that constitute the human body and maintain vital life activities. Functionally, qi serves roles in promoting, warming, defending, consolidating, and facilitating gasification. Thus, qi can regulate the blood, fluids, and essence; maintain body temperature; defend the body; and sustain the overall connectivity between the interior and exterior of the body. Qi transformation refers to the process of metabolism and the mutual transformation of energy among essence, blood, fluids, and other substances. None of this can be separated from the movement of qi; it can be said that qi, in its forms of ascending, descending, outgoing, and incoming, is the fundamental driving force of all life activities (Wang et al., 2023). It is evident that qi serves as the prime mover of all life activities within the human body. Mitochondria produce ATP, which is the primary source of energy for the body and the main source of power for cardiomyocytes, and the normal structure and function of mitochondria are crucial for myocardial energy metabolism (Lopaschuk and Jaswal, 2010). There is a correlation between qi and mitochondria in terms of their origin, morphology, function, and lesions (Lin et al., 2014; Zhang et al., 2001). Systematic reviews and meta-analyses of RCTs show that Qi-regulating formulations, such as Wenxin Keli and Yangxinshi tablet, may be effective and safe for treating ischemic heart disease (IHD) (Wang et al., 2016; Guo et al., 2023). Research h+as found that they play a certain role in regulating cardiac mitochondrial function (Wu et al., 2020), glucose metabolism, lipid metabolism, and amino acid metabolism (Zhang H. et al., 2018; Jiang et al., 2017). The active metabolite Ginsenoside Rb1 from Panax ginseng, known for its qi-tonifying effects, may promote myocardial recovery in AMI via mechanisms involving mitochondrial autophagy, as demonstrated by both in vivo and in vitro studies (Hu et al., 2022). Therefore, tonifying qi may have certain potential in regulating cardiac energy metabolism.

SGMI is made up of Ginseng Rubra Radix; Ophiopogonis Radix; Schisandrae Chinensis Fructus, and the main pharmacodynamic substances include ginsenoside metabolites and lignans. Clinical studies have demonstrated that SGMI can inhibit the inflammatory response in acute-phase AMI patients (Wang LM. et al., 2019). For patients in the recovery phase of AMI, SGMI can enhance clinical efficacy, boost cardiac function, improve tissue perfusion, and optimize oxygen metabolism (Luan et al., 2022). Additionally, it reduces levels of inflammatory factors (Lu and Yao, 2022), restores endothelial function (Tang, 2019), and improves hemorheological parameters (Wang, 2017). Ginsenosides, schizandrin, and ophiopogonin D are the primary active constituents of SGMI. Jiang et al. (2014) investigated the effects of this combination therapy on energy metabolism in rats with AMI and found that it can stimulate fatty acid oxidation and inhibit glycolysis, there by counteracting the metabolic reprogramming associated with AMI (Jiang et al., 2014). Li et al. (2019) found that SGMI can protect the mitochondrial structure of cardiomyocytes from Ang II-induced damage, stabilize mitochondrial membrane potential, and enhance mitochondrial oxygen utilization. Additionally, it can upregulate the expression of genes related to free fatty acid oxidation, glucose oxidation, and mitochondrial biogenesis by activating the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which is crucial for energy metabolism (Li et al., 2019). Zhan et al. (2016) used comparative proteomics techniques to discover that SGMI may exert myocardial protection by modulating multiple energy metabolism pathways: promoting carbohydrate metabolism, inhibiting lipid metabolism, restoring the tricarboxylic acid cycle, and enhancing respiratory chain ATP production (Zhan et al., 2016).

SMI is a compound injection made of Ginseng Rubra Radix and ophiopogonis Radix, and the main pharmacodynamic substances include ginsenosides and ophiopogon saponins (Wang et al., 2020). Studies have found that SMI can alleviate oxidative stress in patients during the acute phase of AMI (Cao et al., 2022), improve vascular endothelial injury and apoptosis (Yang FF. et al., 2017), and enhance hemodynamic parameters (Qin, 2021). For patients in the recovery phase of AMI, SMI can effectively suppress inflammatory responses, reduce blood viscosity, and improve cardiac function (Zhou, 2024; Zhan and Cui, 2023). Wang et al. (2018) utilized network analysis to discover that SMI can significantly reverse the downregulation of energy metabolism-related proteins such as ATP synthase and malate dehydrogenase caused by ischemia, thereby modulating signaling pathways associated with oxidative phosphorylation and mitochondrial dysfunction. In a primary cardiomyocyte model of hypoxic injury in rats, they found that SMI can stabilize mitochondrial membrane potential, restore intracellular ATP levels, increase maximal mitochondrial respiration rate, and enhance oxygen reserve capacity, thus reversing energy metabolic imbalance (Wang Y. et al., 2018). Wang et al. (2019) found that SMI can reduce myocardial cell injury following ischemia-reperfusion (I/R). It increases the expression of glucose transporter 4, cluster of differentiation 36, and fructose-6-phosphate kinase, thereby enhancing the utilization of both free fatty acids and glucose (Wang S. et al., 2019).

SFI is made up of Ginseng Rubra Radix and Aconiti Lateralis Radix Praeparata (black shunpian), and the main active metabolites are ginsenosides and panaxynol (Zheng et al., 2022). For patients with acute-phase AMI, SFI can improve hemodynamic parameters (Zhuo et al., 2018) and reduce levels of inflammatory factors (Jin et al., 2017). For patients in the recovery phase of AMI, SFI can mitigate inflammatory responses (Li et al., 2017), improve hemorheological indicators (You and Wang, 2019), enhance fibrinolytic activity (Zhu et al., 2020), improve vascular endothelial function, and reduce oxidative damage (Jia et al., 2016). Studies have found that SFI can protect against myocardial injury by modulating mitochondrial dynamics, improving mitochondrial energy metabolism, reducing mitochondrial oxidative stress, and inhibiting structural damage to mitochondria (Lu and Xiang, 2023). Bai et al. (2018) investigated the effects of SFI on I/R injury in rats and found that it could enhance the clearance of oxygen free radicals, reduce cellular damage, reduce intracellular Ca²⁺ influx, increase ATP levels, and inhibit inflammation (Bo et al., 2018). Zhan et al. (2024) found that SFI can mediate mitochondrial autophagy in rats with I/R injury by regulating the HIF-1α/BNIP3 pathway, thereby protecting the mitochondrial structure and reducing myocardial cell apoptosis (Zhan et al., 2024). Ji et al. (2011) studied the effects of SFI on myocardial dysfunction following cardiac arrest and resuscitation in pigs and found that it could increase the activity of Na⁺-K⁺-ATPase and Ca²⁺-ATPase, and left ventricular superoxide dismutase, thereby modulating energy metabolism and enhancing antioxidant capacity (Ji et al., 2011). Additionally, Huang et al. (2020) found that Shenfu Formula could synergistically mediate metabolic flexibility of fatty acids and glucose in cardiac energy metabolism in heart failure mice induced by transverse aortic constriction through the AMPK-related pathway, thereby inhibiting cardiac metabolic remodeling (Huang et al., 2020).

AI is an injection made from Astragali Radix, and its main active metabolites include flavonoids, saponins, and amino acids (Yu H. et al., 2019). For patients with acute-phase AMI, AI can improve immune-inflammatory responses and ventricular remodeling (Hou et al., 2012). For patients in the recovery phase of AMI, AI can enhance cellular antioxidant capacity (Zhou et al., 2019), protect vascular endothelium, and increase overall antioxidant ability (Chen et al., 2015). Huang et al. (2018) investigated the effects of major extracts from Astragalus membranaceus on tert-butyl hydroperoxide-induced H9C2 cells and found that they could alleviate oxidative stress and increase cell survival by regulating mitochondrial membrane potential and enhancing mitochondrial bioenergetics parameters, including basal respiration, proton leak, maximal respiration, and non-mitochondrial respiration (Huang et al., 2018). Jin et al. (2014) found that Astragalus can correct impaired free fatty acid and glucose metabolism in AMI model rats, increase myocardial ATP, ADP, and total adenine nucleotide levels, thereby protect ischemic myocardium (Jin et al., 2014). Astragaloside IV, the primary active metabolite of AI, plays a crucial role in regulating cardiac energy metabolism. The underlying mechanisms likely involve multiple pathways: it induces the expression of mitochondria-related proteins (Wang Q. et al., 2021; Zang et al., 2020), protects the structural integrity of cardiac mitochondria (Lu et al., 2015), and modulates mitochondrial function (Dong et al., 2017).

These TCMi-TQs exhibit comparable effects. However, the safety of TCMi has become a growing concern. A retrospective investigation based on China PEACE revealed no benefits of TCMi in patients with acute heart failure (Yu Y. et al., 2019). The annual report on national adverse drug reaction monitoring (2023) revealed 2.627 million cases of suspected adverse drug reactions/events, of which traditional Chinese medicine accounted for 12.6%. Tonifying qi and yin drugs among the top five, and 25.9% of the cases involved injectable drug delivery (National Center For ADR Monitoring C, 2024). Considering the widespread use of TCMi-TQ in the AMI patient population (Spatz et al., 2018), it is necessary to conduct a high-quality systematic evaluation of its efficacy and safety.

This meta-analysis included 113 studies involving 10,779 participants. The results demonstrated that the combined application of TCMi-TQ was more effective in reducing in-hospital mortality, decreasing the occurrence of malignant arrhythmias, reducing the incidence of adverse events, and improving LVEF than biomedicine alone. Safety was also assessed in this meta-analysis, with 32 studies reporting on safety outcomes. No serious adverse events were observed, and the common adverse events included bleeding, ecchymosis, and gastrointestinal discomfort, which could be alleviated through drug withdrawal or symptomatic treatment.

Mortality rate is a crucial indicator reflecting the prognosis of AMI patients (Long et al., 2022). A retrospective study found no significant association between early application of TCMi and in-hospital bleeding or mortality rate in AMI patients (Spatz et al., 2018). However, our study revealed that the combined use of TCMi-TQ significantly reduced AMI mortality, which aligns with the findings of previous systematic reviews examining the effects of SGMI (Lu et al., 2018), SMI (Wang et al., 2015), SFI (Zhu et al., 2018), and AI (Su et al., 2017) in AMI treatment. These findings suggest that TCMi with the specific function of tonifying qi plays a unique role in reducing AMI mortality, possibly due to its comparable effects of regulating energy metabolism. Additionally, this study attempted to investigate the impact of TCMi-TQ combined with CT on the long-term mortality rate of AMI patients. However, due to the limited number of studies evaluating long-term mortality, we were unable to identify potential benefits of TCMi-TQ in long-term mortality, highlighting the need for further research.

Malignant arrhythmia is a significant cause of death in patients with acute myocardial infarction (AMI) (Eryol et al., 2002; Nasution et al., 2020). Studies have consistently demonstrated that malignant arrhythmia accompanies 60%–100% of deaths during the acute phase of AMI (Eldar et al., 1994; Berg et al., 2001). Unfortunately, the benefits of antiarrhythmic drugs for such patients are limited (Piccini et al., 2011). Although a few clinical cases have suggested that TCMi may have adverse effects leading to the occurrence of malignant arrhythmias (Jin, 2013; Zhao et al., 1995; Wu and Li, 1988), a meta-analysis revealed that the combined use of TCMi with tonifying qi properties can reduce the risk of malignant arrhythmias during hospitalization in AMI patients. This reduction in risk may be attributed to the clinical effect of TCMi-TQ in improving myocardial ischemia.

Following myocardial infarction, the loss of myocardial cells leads to myocardial remodeling and the development of heart failure (Author Anonymous, 2020), which significantly impacts the patients’ quality of life and long-term prognosis. LVEF is an essential indicator of cardiac function (McDonagh et al., 2021). This study found that the combined use of TCMi-TQ demonstrates clinically relevant improvements in cardiac function, consistent with previous meta-analysis results (Zhu et al., 2018; Wei et al., 2021). The protective effect of TCMi-TQ on ischemic myocardium may explain this improvement. However, significant heterogeneity was observed in the analysis results, and subgroup analysis and sensitivity analysis did not identify a clear source of heterogeneity. This heterogeneity may be attributed to differences in the ultrasound equipment and technical standards used for LVEF assessment. Therefore, caution must be exercised when interpreting the aforementioned results due to the presence of these heterogeneity factors.

Our meta-analysis results demonstrate that the combined administration of TCMi-TQ does not increase the occurrence of adverse events in AMI patients. Nevertheless, TCMi, when administered through direct bloodstream injection, can be influenced by various factors such as co-solvents, particulates during the manufacturing process, and solvents. This often leads to a higher occurrence of adverse reactions compared to other TCM formulations (Zhang and Niu, 2018). Therefore, healthcare providers should exercise caution in prescribing medications, prioritizing oral formulations. For patients with complex or severe conditions requiring traditional TCM injections, intramuscular administration should be preferred. In emergency situations, TCM injections via intravenous infusion may be necessary (Gao et al., 2012). Healthcare providers should strictly adhere to medication guidelines for the rational and standardized use of TCM injections. Providers should carefully prepare medications, standardize dosages and treatment plans, and accurately identify and document the evidence basis for medication use (Yu et al., 2023). Hospitals should enhance quality control and inspection during the procurement of medications. These TCM injections should be classified, stored separately, and subjected to enhanced supervision and consultation to ensure their proper use. Additionally, hospitals should integrate the quality of TCM intravenous formulations into clinical safety monitoring systems to enable traceability (Peng and Li, 2019). Assigning specialized TCM pharmacists to systematically manage these formulations can further enhance oversight and safety. Research has shown that pharmacist involvement in prescription review, dispensing, drug preparation, and patient counseling significantly reduces the incidence of adverse reactions (Deng et al., 2024). Therefore, hospitals should establish standardized management systems for TCMi and foster effective communication between pharmacists, clinical doctors, and patients to reduce the incidence of adverse reactions.

In summary, this study has the following characteristics compared to previous meta-analyses on TCMi (Mensah et al., 2023): The TCMi included in this study all possess the function of tonifying qi. This is because energy metabolism is one of the main therapeutic principles in TCM for treating AMI, reflecting the representativeness of this study (Suzuki et al., 2023). This study primarily focuses on the observing mortality rate. Meta-analyses of TCMi with mortality, a hard endpoint, as the primary outcome have been relatively rare. The conclusions of this study will provide a more valuable reference for clinical decision-making by healthcare professionals.

The present study underwent a rigorous research process, adhering strictly to a pre-registered protocol. Nonetheless, this meta-analysis still has certain limitations (Mensah et al., 2023): Regarding methodological quality, the overall quality of the included studies is suboptimal, particularly due to insufficient reporting of random sequence generation, allocation concealment methods, blinding implementation, medical follow-up, and independent assessment of the purity/potency of the TCMi-TQ utilized in the studies. These factors may introduce risks of selection bias and performance bias. Researchers should adhere to RCT design standards (Chan et al., 2013) and reporting guidelines (Butcher et al., 2022). In future clinical studies, independent collaborative laboratories should be incorporated, utilizing advanced technologies such as HPLC and GC-MS to assess the purity and efficacy of TCMi-TQ, accurately identify and quantitatively analyze active ingredients, and promote the scientific and standardized generation of high-quality clinical evidence in TCM. This will enhance the rigor and reliability of clinical trials (Suzuki et al., 2023). Regarding long-term efficacy, the included studies fail to evaluate long-term mortality, which limits the assessment of the long-term prognosis of AMI patients receiving TCMi-TQs. It is recommended to expand the evaluation of long-term survival outcomes in AMI patients who receive TCMi-TQs. This would provide a more comprehensive assessment of the clinical significance and practical application value of these treatments (National Center Cardiovascular Diseases, 2024). Regarding heterogeneity, there is notable heterogeneity in the results concerning LVEF, thereby affecting the certainty of the outcomes. These discrepancies may stem from variations in ultrasound equipment and technical standards for LVEF evaluation. To minimize the impact of human factors and ensure consistent, reliable results, it is recommended to enhance the standardization of ultrasound equipment and evaluation techniques (Roger et al., 2010). Regarding the generalizability of research results, all the included studies were conducted within China and involved a single ethnic group. While our findings provide a preliminary foundation for multicenter research, further evaluation is necessary to determine the generalizability of the conclusions. We recommend conducting multicenter trials outside of China to generate more reliable and generalizable clinical evidence.

The present study proposes that integrating TCMi-TQ with conventional biomedicine treatment has a favorable impact on reducing mortality rates, the incidence of malignant arrhythmias, the incidence of adverse events, and enhancing cardiac function among patients with AMI. Given the low methodological quality observed in the included studies, it is imperative to approach this conclusion with caution. Nevertheless, these findings hold significant potential for informing clinical practice guidelines, and we look forward to achieving the scientific integration of TCMi-TQ with standard care in the future.