Clinical study of Yiqi Liangxue Shengji prescription (益气凉血生肌方) for improving cardiac function after myocardial ischemia reperfusion injury in patients with acute myocardial infarction: a randomized, double-blind, placebo-controlled trial

Abstract

OBJECTIVE:

To evaluate the effect of Yiqi Liangxue Shengji prescription (益气凉血生肌方, YQLXSJ) on cardiac function and outcomes in acute myocardial infarction (AMI) patients with myocardial ischemia-reperfusion injury (MIRI) and to determine its clinical efficacy.

METHODS:

This prospective, randomized, double-blind, placebo-controlled trial enrolled hospitalized patients with AMI who underwent percutaneous coronary intervention and experienced MIRI either intraoperatively or postoperatively. Participants were randomly allocated to the treatment group, which received YQLXSJ, or the control group, which received a placebo, concurrent with standard Western Medicine therapy. The intervention period lasted 8 weeks. The primary outcome measure was left ventricular ejection fraction (LVEF), determined by echocardiography. Secondary outcomes included N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) levels, left ventricular internal diameter, major adverse cardiovascular events (MACE), angina pectoris scores, and Chinese medicine evidence scores.

RESULTS:

Following 8 weeks of intervention, the treatment group demonstrated a significant increase in LVEF and a marked reduction in NT-proBNP when compared to the control group. There was also a significant decrease in peak cTnI levels, Chinese medicine evidence scores, and angina pectoris scores. The control group’s left ventricular end-systolic diameter (LVESD) significantly increased compared to baseline after 8 weeks (P < 0.05), whereas the treatment group's LVESD showed no significant change from baseline (P > 0.05). Although the treatment group showed a downward trend in MACE incidence compared to the control group, this difference was not statistically significant (P > 0.05).

CONCLUSIONS:

This study demonstrated that the addition of YQLXSJ to standard therapy can improve cardiac function and alleviate clinical symptoms in AMI patients with MIRI, and also showed a potential to mitigate the incidence of MACE. Furthermore, YQLXSJ displayed a favorable safety profile in clinical application.

1. INTRODUCTION

Acute myocardial infarction (AMI) stands as a pivotal contributor to heightened cardiovascular mortality rates. Although reperfusion therapy is crucial in remains managing AMI, nearly half of the patients treated experience adverse events post-therapy, such as arrhythmias, myocardial tonicity, no-reflow, and microvascular obstruction.¹ These events are known as myocardial ischemia-reperfusion injury (MIRI), which can lead to re-expansion of infarct size, accounting for up to 50% of the total infarct size.² Importantly, infarct size is significantly correlated with the development of heart failure.³ A smaller infarct size is associated with better cardiac function and a reduced incidence of major adverse cardiovascular events (MACE).⁴ Therefore, reducing MIRI and enhancing cardiac function are essential for improving the efficacy of reperfusion therapy and the prognosis of AMI patients.

Modern medical treatments for MIRI include both pharmacologic and non-pharmacologic strategies. Pharmacologic treatments involve the use of anti-inflammatory medications, mitochondria-targeting peptides, adenosine, and sodium nitrite,^5-9 although their clinical efficacy is suboptimal. Non-pharmacological approaches, such as ischemic preconditioning and distal limb ischemia management, have been investigated in clinical studies with inconsistent and controversial outcomes.^10-12 Therefore, the current therapeutic paradigm is considered inadequate.

Yiqi Liangxue Shengji prescription (益气凉血生肌方, YQLXSJ), developed by Prof. LIAO Jiazhen, consists of Huangqi (Radix Astragali Mongolici), Danshen (Radix Salviae Miltiorrhizae), Mudanpi (Cortex Moutan Radicis), and Jinyinhua (Flos Lonicerae). Prof. LIN Qian leads a team in conducting a series of clinical studies. It has demonstrated potential in reducing the incidence of MACE following percutaneous coronary intervention (PCI) for coronary artery disease¹³ and in enhancing quality of life.^14,15 Clinical application in perioperative AMI patients has shown improvements in symptoms of chest pain and fatigue.¹⁶ However, there is a lack of robust clinical evidence regarding its effects on cardiac function and prognosis after MIRI in AMI patients. Consequently, we conducted a randomized, double-blind, placebo-controlled trial to evaluate its clinical efficacy in this context.

2. MATERIALS AND METHODS

2.1. Design and oversight

This prospective, randomized, double-blind, placebo-controlled trial was conducted in the Department of Cardiology at Dongfang Hospital, Beijing University of Traditional Chinese Medicine, from January 2021 to December 2023. The study's objective was to evaluate the effects of adjunctive YQLXSJ on cardiac function and long-term outcomes in AMI patients with MIRI. The study protocol, including all amendments, was approved by the Ethics Committee of Dongfang Hospital, Beijing University of Chinese Medicine (JDF-IRB-2020031103), and registered with the China Clinical Trial Registry (ChiCTR2000038816). Compliance with the Comprehensive Criteria for Reporting Trials (CONSORT) was ensured, and all participants provided informed consent. The trial was supervised through a three-tiered review process involving the Ombudsman of the subject group, the hospital's Ethical Review Center, and the audit team of the Beijing Municipal Health Commission.

2.2. Participants

Seventy-six participants, aged 18 to 80 years, were enrolled in this study. All were diagnosed with AMI and had undergone successful PCI at our hospital, fulfilling the diagnostic criteria for MIRI.^17,18 Chinese medicine identified Qi deficiency, blood stasis, and heat.¹⁹ The MIRI diagnostic criteria were based on the Fourth Universal Definition of Myocardial Infarction (2018).²⁰ Exclusion criteria included acute PCI complications, uncontrolled hypertension, severe comorbidities, severe depletion, or malignancies. Detailed inclusion, exclusion, and diagnostic criteria are provided in the supplementary exhibits 1-4.

2.3. Interventions

Participants were randomly assigned to either the treatment or control groups and received guideline-directed conventional therapy for 8 weeks.^17,18 The intervention began at the time of enrollment. The treatment group received standard treatment plus YQLXSJ, whereas the control group received standard treatment plus a placebo. No additional Chinese or proprietary medicines for AMI were allowed. YQLXSJ was taken as one sachet twice daily. The placebo, which resembled Chinese medicine granules, contained dextrin and 5% of the original Chinese medicine, matching the appearance and taste of YQLXSJ, and was administration in the same manner as YQLXSJ.

2.4. Randomization and blinding

This study utilized a randomized allocation method to evenly form treatment and control groups. A third party was t responsible for generating the random allocation sequence using the random number table method, ensuring the maintenance of blinding. This blinding applied to investigators, participants, testers, and drug administrators. The group assignment was based on the random allocation sequence, with corresponding information enclosed in opaque sealed envelopes. These envelopes were opened after patients met the inclusion and exclusion criteria and were determined to enter the clinical trial. Details of the blinding procedures are provided in the supplementary exhibit 5.

2.5. Drugs preparation

YQLXSJ comprises four herbal components: Huangqi (Radix Astragali Mongolici) (30 g), Danshen (Radix Salviae Miltiorrhizae) (15 g), Mudanpi (Cortex Moutan Radicis) (10 g), and Jinyinhua (Flos Lonicerae) (10 g). YQLXSJ and placebos were obtained from Beijing Tcmages Pharmaceutical Co., Ltd. (Beijing, China). The batch numbers for the granules were as follows: Huangqi (Radix Astragali Mongolici) (20033251), Danshen (Radix Salviae Miltiorrhizae) (20031651, 20032001), Mudanpi (Cortex Moutan Radicis) (20043331), Jinyinhua (Flos Lonicerae) (20035981). The granules underwent preparation through a series of steps including boiling water extraction, concentration, separation, drying, modern pharmaceutical technology granulation, and final packing in medical bags, stored at 4 ℃. Ultra-performance liquid chromatography-tandem mass spectrometry was used to analyze the components, identifying 95 active ingredients in YQLXSJ.²¹

2.6. Sample size

The sample size was calculated based on left ventricular ejection fraction as the primary outcome measure, drawing from data from similar studies.²² Post-treatment, the mean left ventricular ejection fraction (LVEF) was 58% ± 8% in the treatment group and 53% ± 8% in the control group. Accounting for an anticipated 20% dropout rate, a 1:1 allocation ratio was applied to both groups. One-sided tests were performed with α = 0.05 and β = 0.20. Consequently, the total sample size calculated using the formula was 76.²³

2.7. Outcome measurements

The primary outcome measure was left ventricular ejection fraction, assessed via cardiac ultrasound. Secondary outcomes comprised NT-proBNP and cTnI levels, left ventricular internal diameter, major adverse cardiovascular events, angina pectoris scores, and Chinese medicine evidence scores.

Participants underwent daily cTnI level assessments for 7 d postoperatively. Test results obtained from the post-PCI period until treatment enrollment served as baseline data. The peak cTnI level within 7 d post-PCI was recorded.

Participants were monitored for MACE over 1 year, encompassing cardiac death, fatal/non-fatal stroke, myocardial infarction, ACS re-visit or re-hospitalization, repeated reperfusion therapy, coronary artery bypass grafting (CABG), severe arrhythmia, and heart failure. Additionally, all other outcome measures were evaluated at baseline post-PCI and after 8 weeks of treatment to assess efficacy. Supplementary exhibit 6-7 contain details of the Angina pectoris scores scale and Chinese medicine evidence scores scale.

2.8. Statistical analysis

All data underwent analysis using SPSS software version 20.0 (IBM Inc., Armonk, NY, USA). Normally distributed measurement data are presented as mean ± standard deviation; non-normally distributed continuous variables are reported as median (interquartile range, IQR). Categorical data are expressed as frequency (percentage). The t-test was employed when continuous data satisfied normality assumptions. For non-normally distributed continuous variables, comparisons used the Mann-Whitney U test. Categorical data were analyzed with the χ² test (unordered) or Mann-Whitney U/Kruskal-Wallis tests (ordered). A significance level of P < 0.05 was adopted to indicate statistical significance in this study.

3. RESULTS

3.1. Baseline measurements

A total of 76 participants were enrolled in this study (Figure 1). Follow-up was lost for 5 participants, yielding an overall attrition rate of 6.6%. Participants were randomly assigned to the treatment group or control group, with each group initially consisting of 38 participants. In the treatment group, three participants were excluded: one chose alternative Traditional Chinese Medicine and withdrew, and two declined further follow-up. In the control group, two participants were excluded: one voluntarily withdrew and refused follow-up, and the other was lost to follow-up after multiple contact attempts. Ultimately, 71 participants completed both the treatment and follow-up phases. No significant differences in general clinical characteristics were observed between the treatment and control groups (P > 0.05), confirming their comparability (Table 1).

Figure 1. CONSORT 2010 flow diagram.

Table 1.

Baseline characteristics of the patients

Item	Control (n = 36)	Treatment (n = 35)	P value
Baseline characteristic
Age [years, median (IQR)]	63 (55.75, 70.50)	59 (55.00, 63.00)	0.081
Sex [n (%)]
Female	11 (30.56)	9 (25.71)	0.650
Male	25 (69.44)	26 (74.29)
Risk factor [n (%)]
Hypertension	25 (69.44)	17 (48.57)	0.074
Diabetes	15 (41.67)	8 (22.86)	0.090
Dyslipidemia	16 (44.44)	19 (54.29)	0.407
Smoking history	15 (41.67)	21 (60.00)	0.122
Drinking history	5 (13.89)	11 (31.43)	0.077
Family history of coronary	7 (19.44)	8 (22.86)	0.725
Medical history [n (%)]
Myocardial infarction	4 (11.11)	4 (11.43)	1.000
Percutaneous coronary intervention	4 (11.11)	5 (14.29)	0.964
Presentation feature ($\overline{x}\pm s$)
Systolic blood pressure (mm Hg)	130.22±19.24	121.49±19.81	0.064
Diastolic blood pressure (mm Hg)	78.67±12.53	72.86±12.80	0.057
Heart rate (beats/min)	78.89±14.79	76.43±13.22	0.463
Culprit lesion [n (%)]
Left anterior descending branch	21 (58.33)	17 (48.57)	0.278
Left circumflex branch	8 (22.22)	14 (40.00)
Right coronary artery	6 (16.67)	4 (11.43)
Left main coronary artery	1 (2.78)	0 (0.00)
Type of vascular lesion [n (%)]
Single-vessel lesion	12 (33.33)	11 (31.43)	0.945
Double vessel lesion	13 (36.11)	14 (40.00)
Three-vessel disease	11 (30.56)	10 (28.57)
Characteristic of myocardial infarction
STEMI [n (%)]	25 (69.44)	24 (68.6)	0.937
NSTEMI [n (%)]	11 (30.56)	11 (31.43)
Infarctional Q wave [n (%)]	18 (50.00)	13 (37.14)	0.275
Non-infarctional Q wave [n (%)]	18 (50.00)	22 (62.86)
With arrhythmia [n (%)]	5 (13.88)	9 (25.71)	0.211
No arrhythmia [n (%)]	31 (86.11)	26 (74.29)
Number of cardiac stents [median (IQR)]	1.00 (1.00, 2.00)	1.00 (1.00, 2.00)	0.325
Number of drug balloons [median (IQR)]	0.00 (0.00, 1.00)	0.00 (0.00, 1.00)	0.669

Notes: the treatment group received standard treatment plus YQLXSJ, whereas the control group received standard treatment plus a placebo. YQLXSJ: Yiqi Liangxue Shengji prescription; IQR: interquartile range; STEMI: ST-segment elevation myocardial; NSTEMI: non-ST-segment elevation myocardial infarction Data are shown as median (IQR) or n (%). The t-test was employed when continuous data satisfied normality assumptions. For non-normally distributed continuous variables, comparisons used the Mann-Whitney U test. Categorical data were analyzed with the χ ² test (unordered) or Mann-Whitney U/Kruskal-Wallis tests (ordered). A significance level of P < 0.05 was adopted to indicate statistical significance in this study.

3.2. Primary outcome: LVEF

A total of 58 patients completed the indicator measurements, with 29 in each group (treatment and control). Comparing pre- and post-treatment effects, the LVEF in the treatment group significantly increased after 8 weeks of treatment relative to baseline (57.3% ± 10.2% vs 63.9% ± 8.3%, P < 0.001). In contrast, the control group showed a slight increase in LVEF post-treatment compared to baseline, but this change was not statistically significant (57.6% ± 10.4% vs 57.7% ± 9.9%, P = 0.941).

After treatment, the treatment group had significantly higher LVEF than the control group (63.9% ± 8.3% vs 57.7% ± 9.9%, P = 0.012). The treatment group also showed greater improvement in cardiac function.

3.3. Secondary outcomes

3.3.1. NT-proBNP

A total of 54 patients completed the indicator measurements, with 28 in treatment group and 26 in the control group. Following 8 weeks of treatment, NT-proBNP levels in both groups were non-normally distributed, necessitating non-parametric tests for analysis.

Comparing pre- and post-treatment effects, the NT-proBNP levels in the treatment group significantly decreased after 8 weeks of treatment relative to baseline [524.0 (123.0, 1780.0) vs 164.1 (43.4, 581.1) pg/mL, P < 0.001]. Similarly, the NT-proBNP levels in the control group showed a significant decrease post-treatment compared to baseline [860.3 (333.1, 1650.5) vs 277.8 (154.0, 878.3) pg/mL, P = 0.002]. After treatment, the treatment group had significantly lower NT-proBNP levels than the control group [164.1 (43.4, 581.1) vs 277.8 (154.0, 878.3) pg/mL, P = 0.036]. As NT-proBNP serves as an indirect marker of cardiac function, these findings suggest superior cardiac functional improvement in the treatment group.

3.3.2. cTnI levels

A total of 61 patients completed the index measurements, with 29 in the treatment group and 32 in the control group. The cTnI levels in both groups were not normally distributed, warranting the use of nonparametric tests for analysis. Patients were enrolled immediately following MIRI post-PCI, with serial monitoring of cTnI levels. Final analysis utilized peak cTnI levels within 7 postoperative days.ΔcTnI was calculated as peak minus baseline levels.

Comparing pre- and post-treatment effects, the treatment group showed a non-significant increase from baseline to peak [1.53 (0.33, 4.47) vs 2.39 (0.62, 11.68) ng/mL, P = 0.417], whereas the control group demonstrated a significant increase from baseline to peak [0.78 (0.20, 3.93) vs 7.52 (0.69, 34.10) ng/mL, P < 0.001]. After treatment, the treatment group showed no significant difference in cTNI peak levels versus the control group [2.39 (0.62, 11.68) vs 7.52 (0.69, 34.10) ng/mL; P > 0.05]. However, the treatment group versus the control group had significantly attenuated cTnI elevation as measured by ΔcTnI [0.27 (—2.17, 8.99) vs 4.90 (0.11, 25.82) ng/mL; P = 0.048]. These findings indicate substantially mitigated perioperative myocardial injury in the treatment group relative to controls.

3.3.3. Left ventricular internal diameter

A total of 57 patients completed the index measurements, with 28 in the treatment group and 29 in the control group. The left ventricular internal diameter encompasses both the left ventricular end-systolic diameter (LVESD) and the left ventricular end-diastolic diameter (LVEDD).

Comparing pre- and post-treatment effects, the LVEDD in the treatment group significantly increased after 8 weeks of treatment relative to baseline [(48 ± 5) vs (51 ± 4) mm; P = 0.023). Similarly, the LVEDD in the control group significantly increased relative to baseline [(48 ± 4) vs (50 ± 5) mm; P = 0.016]. After treatment, the treatment group showed no significant difference in LVEDD versus the control group [(51 ± 4) vs (50 ± 5) mm; P = 0.609].Comparing pre- and post-treatment effects, the LVESD in the treatment group showed a slight reduction after 8 weeks relative to baseline [(33 ± 5) vs (33 ± 5) mm; P = 0.626]. In contrast, the LVESD in the control group significantly increased relative to baseline [(32 ± 5) vs (34 ± 6) mm; P = 0.029]. After treatment, there was no significant difference in LVESD between the treatment and control groups [(33 ± 5) vs (34 ± 6) mm; P = 0.249]. These findings indicate that deterioration of myocardial contractile function was suppressed in the treatment group.

3.3.4. MACE

A total of 71 participants were included in the followed up, with those who withdrew from the study excluded. Investigators conducted telephone and outpatient follow-ups until December 2023 to ensure complete follow-up.

In terms of MACE, six participants in the treatment group and ten in the control group experienced such events (χ² = 1.15, P = 0.284). Regarding PCI, three participants in the treatment group and four in the control group were involved (P = 0.516). For CABG, one participant in the treatment group and none in the control group had this event (P = 0.493). In the case of lethal stroke, one participant in the treatment group and none in the control group were affected (P = 0.493). As for cardiac death, no participant in the treatment group and one in the control group had this outcome (P = 0.507). Regarding heart failure, one participant in the treatment group and four in the control group experienced it (P = 0.187). Finally, for Recurrent Myocardial Infarction, no participant in the treatment group and one in the control group had this event (P = 0.507).

MACE occurrence served as the endpoint event, and survival curves were generated using the Kaplan-Meier method. Differences in survival were evaluated using the log-rank test. While a declining trend in MACE incidence was observed in the treatment group compared to the control group, the disparity was not statistically significant (χ² = 1.15, P = 0.28) (Figure 2).

Figure 2. Survival curves for both groups of participants.

3.3.5. Angina pectoris scores

A total of 71 patients completed the index measurements, with 35 in the treatment group and 36 in the control group. Angina pectoris scores were evaluated both at baseline (Week 0) and at Week 8 after intervention. In the treatment group, the angina pectoris scores significantly decreased from baseline to Week 8 [18 (16, 20) vs 4 (0, 6); P < 0.001]. Similarly, in the control group, the angina pectoris scores also decreased significantly from baseline to Week 8 [18 (16, 20) vs 8 (6, 12); P < 0.001]. After treatment, the treatment group showed significantly lower angina pectoris scores compared to the control group [4 (0, 6) vs 8 (6, 12); P < 0.001].

3.3.6. Chinese medicine evidence scores

A total of 71 patients completed the index measurements, with 35 in the treatment group and 36 in the control group. Chinese medicine evidence scores were evaluated both at baseline (Week 0) and at Week 8 after intervention. In the treatment group, the Chinese medicine evidence scores significantly decreased from baseline to Week 8 [(23 ± 3) vs (12 ± 4); P < 0.001]. Similarly, in the control group, the Chinese medicine evidence scores also decreased significantly from baseline to Week 8 [(23 ± 4) vs (16 ± 4); P < 0.001]. After treatment, the treatment group showed significantly lower Chinese medicine evidence scores compared to the control group [(12 ± 4) vs (16 ± 4); P < 0.001].

3.4. Adverse event

Over the 8-week treatment period, one adverse event was reported in the treatment group, where a patient experienced diarrhea, with three episodes of stools daily, alleviated upon cessation of the medication. During the follow-up, a single case of gastrointestinal bleeding was recorded in the treatment group, attributed to a "colonic ulcer". This event was deemed unrelated to Traditional Chinese Medicine, based on the patient's medical history and medication timeline.

In contrast, the control group reported no adverse events during the treatment phase. However, one case of gastrointestinal bleeding was observed during the follow-up period. Nevertheless, since the patient had discontinued placebo usage for over 2 months, the incident was deemed unrelated to the placebo.

In summary, neither group recorded any serious adverse events. The events that occurred were typically self-relieving or resolved following medication withdrawal. Additionally, most adverse events were unrelated to Traditional Chinese Medicine treatment, indicating an overall high level of safety.

3.5. Combination medication situation

The participants in both groups received standard Western medical treatment, including dual antiplatelet drugs, lipid-lowering drugs, nitrates, β-blockers, calcium antagonists, ACEI/ARB, low-molecular-weight heparin, diuretics, and cardiotonic agents. Statistical analysis indicated no significant difference between the groups, ensuring comparability (P > 0.05) (Table 2).

Table 3.

Combination medication situation [n (%)]

Drug	Treatment	Control	χ 2 value	P value
Dual antiplatelet drugs	34 (97.14)	35 (97.22)	0.000	1.00
Lipid-lowering drugs	34 (97.14)	35 (97.22)	0.000	1.00
Nitrates	10 (28.57)	13 (36.11)	0.461	0.497
β-blockers	21 (60)	26 (72.22)	1.185	0.276
Calcium antagonists	3 (8.57)	5 (13.89)	0.111	0.739
ACEI/ARB	19 (54.29)	27 (75.00)	3.338	0.068
Low-molecular heparin, diuretics	33 (94.29)	35 (97.22)	0.001	0.980
Diuretics	5 (14.29)	6 (16.67)	0.077	0.782
Cardiotonic agents	3 (8.57)	1 (2.78)	0.296	0.587

Notes: the treatment group received standard treatment plus YQLXSJ, whereas the control group received standard treatment plus a placebo. YQLXSJ: Yiqi Liangxue Shengji prescription; ACEI: angiotensin-converting enzyme inhibitors; ARB: angiotensin II receptor blocker. Data are shown as n (%). Categorical data were analyzed with the χ ² test. A significance level of P < 0.05 was adopted to indicate statistical significance in this study.

4. DISCUSSION

Myocardial injury due to MIRI in patients with AMI can account for up to 50% of the final infarct size.² The enlargemen of the infarct size not only impairs cardiac function but also adversely affects patient prognosis, contributing to a reduced quality of life and heart failure.²⁴ Hence, reducing MIRI to minimize the infarct size, enhance cardiac function, and improve patient outcomes is an urgent clinical need.

Several clinical studies have explored therapeutic interventions aimed at preventing reperfusion injury and to assessing infarct size, cardiac function, and prognosis indicators in AMI patients, with mixed results. For example, the IL-1 receptor antagonist anakinra reduced inflammatory markers in patients with non-ST-segment elevation myocardial infarction but was associated with an increased incidence of MACE within one year.⁵ A clinical study suggested that post-ischemic management with inflation and deflation cycles using a plain balloon after PCI could improve cardiac function and reduce myocardial infarct size in AMI patients,²⁵ However, the DANAMI-3-DEFER trial, which included 510 patients with ST-segment elevation myocardial infarction (STEMI), indicated that such post-ischemic management did not reduce myocardial infarct size or the incidence of microvascular obstruction.²⁶ Furthermore, while one study showed a reduction in the risk of acute MIRI through distal ischemic treatment,²⁷ a randomized controlled trial involving 5,401 STEMI patients found that remote ischemic conditioning did not improve the 12-month rate of heart failure hospitalization or the risk of cardiac death.¹¹

Traditional Chinese Medicine scholars commonly attribute the underlying pathogenesis of MIRI to Qi deficiency and blood stasis.²⁸ They propose that treatment should focus on enhancing Qi and promoting blood circulation.^29,30 In this study, we employed the clinically established formula YQLXSJ, which has been in use for over two decades. This formula, comprising Huangqi (Radix Astragali Mongolici), Danshen (Radix Salviae Miltiorrhizae), Mudanpi (Cortex Moutan Radicis), and Jinyinhua (Flos Lonicerae), is recognized for its multifaceted effects, including enhancing Qi, promoting blood circulation, cooling blood, and fostering muscle growth, and has been awarded a national patent. Our preliminary research indicates that YQLXSJ can aid in the recovery from hypoxia/ reoxygenation-induced damage to vascular endothelial cells, potentially through improving endothelial cell energy metabolism, reducing oxidative stress, inhibition of AMPK activation, and modulation of the mammalian target of rapamycin protein complex 1 signaling pathway.³¹ Furthermore, YQLXSJ is shown to elevate serum NO levels, suppress the TLR4/NF-κB pathway to reduce inflammation, encourage vascular endothelial cells proliferation and repair, and curb the proliferation and migration of vascular smooth muscle cells.^32,33

The clinical efficacy of YQLXSJ in perioperative AMI patients is significant, with symptoms relief such as chest pain and fatigue.¹⁶ Our study enrolled 76 AMI patients who experienced MIRI following PCI. LVEF served as the primary outcome measure to assess cardiac function post-MIRI in AMI patients. The study also evaluated cTnI levels, Traditional Chinese Medicine evidence scores, angina severity, and MACE, providing a comprehensive assessment of cardiac function, myocardial injury, TCM efficacy, and patient prognosis.

The study results revealed a significant enhancement in LVEF and a marked reduction in NT-proBNP levels within the treatment group as compared to the control group, indicating an improvement in cardiac function in AMI patients with MIRI. Over the course of 8 weeks of treatment, LVESD increased significantly in the control group (P < 0.05), whereas the treatment group displayed a non-significant trend towards reduction (P > 0.05), suggesting a potential effect on inhibiting ventricular remodeling. Furthermore, the treatment group showed a significantly greater reduction in cTnI peak levels, suggesting less myocardial injury. Clinical symptom alleviation was apparent, with the treatment group demonstrating significantly lower scores for Chinese medicine evidence and angina pectoris compared to the control group. Although MACE showed a decreasing trend in the treatment group compared to controls (P > 0.05), no significant difference was observed. Although the study did not demonstrate statistically significant differences in MACE, a downward trend was noted. The therapeutic effects, as indicated by improvements in LVEF and NT-proBNP, suggest that the treatment yields favorable clinical outcomes for MIRI. This implies that YQLXSJ could be a valuable adjunct to the clinical management of MIRI. Future studies should consider a randomized controlled trial with MACE as the primary endpoint to assess its long-term prognostic impact.

However, the study had several limitations. Firstly, while YQLXSJ demonstrated clinical benefits, its active ingredients and mechanism of action remain unclear, necessitating further basic research. Secondly, the study's homogenous Chinese ethnicity participants raise questions about the generalizability of findings to other ethnicities. Lastly, due to the impact of COVID-19, both doctors and patients have experienced difficulties, and some follow-up indicators for participants are missing. At the same time, considering the difficulties in subject recruitment, we reduced the sample size after calculations to ensure the feasibility of the project. Although the sample size can meet the requirements for statistical significance, it is still a regret in this study. The variation in sample sizes for specific indicators between the two groups resulted from random factors attributed to the pandemic's influence. A smaller sample size potentially limits the statistical power to detect genuine differences in effects, necessitating a more cautious interpretation of the findings.

In conclusion, this study demonstrated that the addition of YQLXSJ to standard therapy can improve cardiac function and alleviate clinical symptoms in AMI patients with MIRI, and also showed a potential to mitigate the incidence of MACE. Furthermore, YQLXSJ displayed a favorable safety profile in clinical application.

5. SUPPORTING INFORMATION

Supporting data to this article can be found online at http://www.journaltcm.com.

Funding Statement

Supported by the Capital’s Funds for Health Improvement and Research: Clinical Study on Yiqi Liangxue Shengji Prescription for Improving Cardiac Function after Myocardial Ischemia Reperfusion Injury in Patients with Acute Myocardial Infarction (CFH 2020-4-4204); Beijing University of Traditional Chinese Medicine Qihuang Yingcai·Excellent Young Science and Technology Talent Cultivation Program (K2023A03); Beijing University of Traditional Chinese Medicine Dongfang Hospital High-level Capacity Building Project "Zhuoyuan" Project National Talent Precision Cultivation Program (DFRCZY-2024GJRC012)