Assessment of complementary treatment with Yiqi Fumai lyophilized injection on acute decompensated ischemic heart failure (ACT-ADIHF): a multicenter randomized controlled trial

doi:10.21203/rs.3.rs-3093131/v1

Background

To evaluate the efficacy and safety of Yiqi Fumai lyophilized injection in treating acute decompensated ischemic heart failure (ADIHF).

Methods

666 patients with ADIHF from 37 clinical research centers in China were randomly allocated to the treatment group (n = 332) and the control group (n = 334). The control group was treated with standardized western medicine. The treatment group received intravenously 5.2g Yiqi Fumai lyophilized injection based on standardized western medicine for 7 days.

Results

There was no statistically significant difference in baseline characteristics between the two groups (P > 0.05). After treatment, the BNP level in the treatment group was significantly lower than that in the control group (8 days: 465.0 pg/ml vs. 533.6 pg/ml, P < 0.05; 60 ± 3 days: 398.0 pg/ml vs. 464.0 pg/ml, P < 0.01). The percentage of BNP level reduced by more than 30% compared to baseline was significantly higher in the treatment group than that in the control group (P < 0.01). And the improvement of LVEF, NYHA cardiac functional classification, MLHFQ score, and TCM four diagnosis information score were better in the treatment group than those in the control group at 60 ± 3 days after enrollment (P < 0.05 or P < 0.01). There were no statistically significant differences in the incidence of composite endpoint events and adverse events (P > 0.05).

Conclusion

Based on standardized western medicine, using Yiqi Fumai lyophilized injection can further reduce the plasma BNP level, improve cardiac function, alleviate clinical symptoms, improve the quality of life in patients with ADIHF, and it is safe.

ischemic heart failure

acute decompensation

traditional Chinese medicine

randomized controlled trial

Yiqi Fumai lyophilized injection

With the advancement in the treatment of coronary heart disease, the survival time of patients has been prolonged, and the number of ischemic heart failure (IHF) patients has been accumulating and increasing (Fox et al., 2001; Lala et al., 2014). Compared with patients in the stable stage of chronic heart failure (HF), patients in acute decompensation have worse cardiac function and quality of life, more severe clinical symptoms, and often require emergency treatment or hospitalization. The inpatient mortality rate is 3%, and the 1-year mortality rate is as high as 25–40% (Heart Failure Group of Chinese Society of Cardiology of Chinese Medical Association et al., 2018; Parikh et al., 2019). Previous experience has shown the unique advantages of traditional Chinese medicine (TCM) in improving the clinical condition of patients with acute decompensated ischemic heart failure (ADIHF) (Wang et al., 2019).

The Chinese patent medicine Yiqi Fumai lyophilized injection is an innovative TCM preparation developed according to modern technology with Hongshen (Ginseng Radix et Rhizoma Rubra), Maidong (Ophiopogonis Radix), Wuweizi (Schisandrae Chinensis Fructus) as raw materials, which has the characteristics of supplementing Qi and restoring pulse, nourishing Yin, and generating fluid. It is often widely used in the treatment of ADIHF. Meta-analysis has suggested that based on standardized western medicine, using Yiqi Fumai lyophilized injection may further improve cardiac function, improve clinical efficacy, increase left ventricular ejection fraction (LVEF) and reduce N-terminal pro-brain natriuretic peptide level in HF patients (Wang et al., 2016a). However, the reliability of the results was affected by the overall low quality of the included literature. This study was conducted with a standardized multicenter, randomized, controlled study design to evaluate the efficacy and safety of Yiqi Fumai lyophilized injection in treating patients with ADIHF (Qi and Yin deficiency syndrome) and to provide higher-quality clinical evidence.

2.1 Study Design

This study is a multicenter, randomized, controlled trial, including subjects from 37 clinical research centers in China from October 2015 to October 2018. This study was conducted following the principles of the Declaration of Helsinki, and all subjects signed informed consent.

The protocol has been approved by the Ethics Committee of First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and the ethics committee of each participating research center (approval number: TYLL2015 [K] 004), registered on the Chinese Clinical Trial Registry (http://www.chictr.org.cn) (registration number: ChiCTR-IPR-15007396), and was published in Cardiovascular Drugs and Therapy in April 2018 (Wang et al., 2018).

2.2 Patient Screening Criteria

The inclusion criteria were as follows: (1) Age 40–79. (2) Diagnosed with coronary heart disease (meeting one of the following conditions): (a) having a history of old myocardial infarction; (b) coronary angiography or computed tomography angiography (CTA) showing the lumen diameter of at least one main branch of the coronary artery was narrowed by more than 50%, with or without revascularization (percutaneous coronary intervention or coronary artery bypass grafting). (3) Meet the diagnostic criteria of acute decompensated chronic HF (Chinese Society of Cardiology of Chinese Medical Association and Editorial Board of Chinese Journal of Cardiology, 2014). (4) New York Heart Association (NYHA) classification Ⅲ~Ⅳ. (5) Brain natriuretic peptide (BNP) > 200 pg/ml. (6) Sign informed consent.

The exclusion criteria were as follows: (1) First diagnosis of acute HF. (2) Suffering from any of the following diseases: (a) acute coronary syndrome, (b) hypotension (systolic blood pressure < 90 mmHg), (c) cardiogenic shock, (d) resistant hypertension (systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg), (e) second degree and above sinoatrial or atrioventricular block without a pacemaker, uncontrolled malignant arrhythmia, (f) severe heart valve diseases, (g) dilated cardiomyopathy, (h) hypertrophic obstructive cardiomyopathy, (i) myocarditis, (j) pulmonary embolism, (k) pulmonary heart disease, (l) stroke within 6 months, etc. (3) Scheduled revascularization treatment or cardiac resynchronization therapy within 2 months. (4) Liver function alanine aminotransferase is more than three times the upper limit of normal. (5) Serum creatinine is more than two times the upper limit of normal. (6) Severe endocrine disease such as hyperthyroidism. (7) Hemoglobin ≤ 9g/dL. (8) Mental disorders. (9) Malignant tumors. (10) Pregnant or planning pregnancy, breastfeeding mothers. (11) Suspected or diagnosed with allergy to intervention drug. (12) Participated in other research within 2 months.

2.3 Randomization and Intervention

The subjects were divided into the treatment group and the control group according to the ratio of 1:1. Two groups received standardized western medication. Antiplatelet agents, statins, diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, β-blockers, and aldosterone receptor antagonists were used as long as there were no contraindicated. Based on standardized western medicine, the treatment group was given intravenously 5.2 g Yiqi Fumai lyophilized injection (specification: 0.65g per bottle, Tasly Pharmaceutical Co., Ltd., Tianjin, China. Product batch number: 20150303/20150604) + 250 ml 5% glucose/sodium injection at a rate of 60 ml/h (infusion pump recommended) once daily. The main ingredients of Yiqi Fumai lyophilized injection are Ginseng Radix et Rhizoma Rubra, Ophiopogonis Radix, Schisandrae Chinensis Fructus, and the auxiliary materials are meglumine and mannitol. The patients received the intervention for 7 days without any other TCM preparations. Outcomes were assessed at baseline, 8 days, 30 ± 3 days, and 60 ± 3 days after randomization.

2.4 Outcomes

The primary efficacy outcome was plasma BNP level. Secondary efficacy outcomes included NYHA cardiac function classification, LVEF (The modified Simpson method was used for measurement by a specialist in each center.), Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, TCM four diagnosis information score, and composite endpoint events (all-cause death, HF emergency/readmission, acute coronary syndrome, revascularization, malignant arrhythmia, cardiogenic shock, stroke, and pulmonary embolism). The safety outcome was the incidence of adverse events.

2.5 Sample Size Estimation

The sample size was calculated based on the rate of a 30% decrease in BNP levels after treatment. The subjects were arranged in a ratio of 1:1 into the treatment group or the control group. It is assumed that standardized western medicine can reduce the BNP level by > 30–60%, and integrated traditional Chinese and western medicine intervention can reduce the BNP level by > 30–70%. The significance level α is 0.05, and the power (1-β) is 0.80 in the one-sided test. In addition, the incomplete rate is considered to be no more than 20%, the sample size of each group was 333. The calculation formula is as follows:

2.6 Statistical Analysis

Statistical analysis was independently completed by a third-party institution, the Medical Statistics Office of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine. All statistical tests were performed using SAS 9.4 software, and the full analysis set (FAS) was used to evaluate efficacy. When the measurement data conform to the normal distribution, the mean ± standard deviation (m ± SD) was used for statistical description; otherwise, the median (interquartile range) [Med (Q1, Q3)] was used. The paired t-test or nonparametric test was used in comparison within groups; the group t-test or nonparametric test was used in the comparison between groups. The number of cases (percentage) [n (%)] was used for the statistical description of enumeration data; χ² test or Fisher’s exact test was used for comparison of categorical data between groups; Wilcoxon rank-sum test was used for comparison of hierarchical data between groups. All statistical tests were two-sided, and P < 0.05 was considered statistically significant.

3.1 Baseline Characteristics

Six hundred sixty-six subjects were enrolled, including 332 in the treatment group and 334 in the control group. The FAS included 317 cases in the treatment group and 322 cases in the control group; the per-protocol set included 294 cases in the treatment group and 296 cases in the control group; the safety set included 327 cases in the treatment group and 330 cases in the control group (Figure 1). There was no significant difference between the two groups in terms of demographic characteristics, disease history, basic medication situation, and the plasma BNP level, NYHA cardiac function classification, LVEF, MLHFQ scores, TCM four diagnosis information score, and groups were comparable (P > 0.05) (Table 1).

3.2 Primary outcome

Compared with the baseline level, the plasma BNP level was significantly lower at 8 days, and 60 ± 3 days after enrollment, the plasma BNP level in the treatment group was lower than that in the control group (8 days: 465.0 pg/ml vs. 533.6 pg/ml, P < 0.05; 60 ± 3 days: 398.0 pg/ml vs. 464.0 pg/ml, P < 0.01) (Table 2). At 8 days and 60 ± 3 days after enrollment, the rate of patients with BNP decreased by more than 30% in treatment group was higher than that in control group (8 days: 55.21% vs. 41.93%, P < 0.001; 60 ± 3 days: 62.46% vs. 51.24%, P < 0.01).

3.3 Secondary Outcomes

3.3.1 NYHA cardiac function classification

The NYHA cardiac function classifications of two groups were improved at 8 days and 60 ± 3 days after enrollment, and the improvement in the treatment group was significantly better than that in the control group (8 days: P < 0.01; 60 ± 3 days: P < 0.001) (Table 3).

3.3.2 LVEF

After 60 ± 3 days after enrollment, the LVEF of the two groups increased compared with the baseline level, and the LVEF in the treatment group was higher than that in the control group at 60 ± 3 days (P < 0.01) (Table 4).

3.3.3 MLHFQ scores

After 60 ± 3 days after enrollment, the MLHFQ scores of the two groups decreased compared with the baseline level, and the MLHFQ scores in the treatment group were lower than that in the control group (P < 0.05) (Table 4).

3.3.4 TCM four diagnostic information score

At 8 days and 60 ± 3 days after enrollment, the TCM four diagnostic information scores of the two groups decreased compared with baseline level, and the TCM four diagnostic information scores in the treatment group were lower than those in the control group (8 days: P < 0.05; 60 ± 3 days: P < 0.01) (Table 5).

3.3.5 Compound endpoint events

The compound endpoint events were 22.71% in the treatment group and 25.16% in the control group. All-cause death was 3.47% in the treatment group and 4.35% in the control group. The incidence of HF readmission was 8.83% in the treatment group and 9.32% in the control group, and the incidence of cardiovascular events was 19.24% in the treatment group and 20.81% in the control group, respectively. There was no significant difference between groups (P > 0.05).

3.4 Safety evaluation

There were 18 cases (5.50%) and 14 cases (4.24%) of adverse events in the treatment and control groups, respectively. There was no significant difference between the two groups (P= 0.4524). Among them, there was one serious adverse event in the treatment group and the control group, which was duodenal perforation and cholelithiasis with biliary colic. In the treatment group, 2 cases were judged to be drug-related adverse reactions (aversion to cold, fever, tremor of limbs, chest tightness, shortness of breath in 1 case; chills in 1 case), and there was no significant difference between groups (P > 0.05) (Table 6).

At present, the standardized western medicine treatment of HF is diuretic, vasodilator and positive inotropic drugs, which can improve the symptoms of patients in the short term, but long-term application may have adverse reactions such as electrolyte disturbance and malignant arrhythmia. The combined use of TCM on the basis of standardized standardized western medication has potential advantages in optimizing the treatment of HF. Qi and Yin deficiency syndrome is one of the primary TCM syndromes in acute decompensated chronic HF (Zhao et al., 2013). The Chinese patent medicine Yiqi Fumai lyophilized injection is made of Hongshen (Ginseng Radix et Rhizoma Rubra), Maidong (Ophiopogonis Radix), Wuweizi (Schisandrae Chinensis Fructus) as raw materials, which has the characteristics of supplementing Qi and restoring pulse, nourishing Yin, and generating fluid.

Modern pharmacological studies have shown that ginsenoside in Yiqi Fumai lyophilized injection could inhibit the activity of Na⁺-K⁺-ATPase, and promote the influx of Ca²⁺, thus enhancing myocardial contractility and improving cardiac function (Wang et al., 2016b). Ginsenoside Rb1 can protect endothelial cells by inhibiting apoptosis, thus delaying vascular injury (Zhou et al., 2005), and ginsenoside Rb2 can significantly alleviate a malignant chain reaction such as oxidative stress and inflammation in ischemia-reperfusion models (Xue et al., 2020). The polysaccharide of Ophiopogonis Radix has the role of protecting myocardial cells, improving blood flow, inhibiting the increase of free radicals caused by myocardial ischemia and clearing oxygen free radicals, and can expand coronary arteries and increasing coronary blood flow (Xu et al., 2004). Schisandrae Chinensis Fructus can obviously improve the common hypoxia tolerance of animals and has a strong protective effect on acute myocardial ischemia injury in animals (Qi et al., 2011). Basic studies have shown that Yiqi Fumai lyophilized injection could improve the cardiac function of ischemic HF rats by increasing plasma levels of omentin, PI3K/Akt, AMPK, and inhibiting MAPKs levels (Li et al., 2019), suggesting that it has a reliable mechanism for improving IHF. In addition, Yiqi Fumai lyophilized injection can improve mitochondrial function by regulating ROS production and the CaMKII signal pathway. Thus, the cardiac contractile function, cardiac structural damage, cardiac histological characteristics, and fibrosis of mice with HF induced by coronary artery ligation can be alleviated (Zhang et al., 2019).

BNP mainly originates from ventricles and is a member of the diuretic natriuretic peptide family generated and secreted by cardiac myocytes, which have the effects of diuresis, vasodilator, and inhibition of the sympathetic nervous system. During acute decompensated heart failure, ventricular pressure is overloaded, and blood volume increases, stimulating cardiomyocytes to synthesize BNP and release it into the blood, resulting in increased plasma BNP levels. Studies have shown that BNP is an important prognostic marker for HF patients, and its concentration is closely correlated with patient survival rates. A BNP reduction of more than 30% indicates a reduced risk of readmission and death (Ruocco et al., 2016). This study showed that the standardized western medicine combined with Yiqi Fumai lyophilized injection for 7 days could significantly reduce BNP level, improve cardiac function, alleviate clinical symptoms and improve quality of life in IHF patients. The improvement of LVEF appeared at 60 ± 3 days after enrollment, which might be related to the long-term effect of Yiqi Fumai lyophilized injection. At 60 ± 3 days after enrollment, the incidence of composite endpoint events in the treatment group was lower than that in the control group. Still, no statistical difference was observed, indicating that the improvement of LVEF was not synchronized with the amelioration of long-term endpoint events.

Regarding safety evaluation, this study showed that there were 3 cases of adverse reactions in the treatment group, all of which were known adverse reactions in the instructions of Yiqi Fumai lyophilized injection. Adverse reactions may be related to patients’ complex underlying diseases and individual differences. There were no statistically significant differences in adverse events and laboratory indicators between the two groups. In addition, as a traditional Chinese medicine freeze-dried powder preparation, the use and preservation of Yiqi Fumai lyophilized injection should strictly follow the standards to avoid iatrogenic adverse reactions.

In this study, a multicenter, randomized, controlled study design was used to carry out a large sample clinical trial. The results can provide high-quality evidence for clinical decision making. However, this study has some limitations: there were no statistical differences in HF readmission, cardiovascular events, all-cause death, and other endpoint events due to the relatively short follow-up time. Further studies with longer follow-ups and more focus on endpoint events may provide more evidence of prognosis.

Based on standardized western medicine, Yiqi Fumai lyophilized injection can further reduce plasma BNP level, improve cardiac function, alleviate clinical symptoms and improve quality of life in patients with ADIHF and has good safety.

ADIHF: acute decompensated ischemic heart failure; BNP: brain natriuretic peptide; CTA: computed tomography angiography; FAS: full analysis set; HF: heart failure; IHF: ischemic heart failure; LVEF: left ventricular ejection fraction; MLHFQ: Minnesota Living with Heart Failure Questionnaire; NYHA: New York Heart Association; TCM: traditional Chinese medicine.

Funding

This work was supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No. ZYYCXTD-C-202203), the National Administration of Traditional Chinese Medicine: 2019 Project of Building Evidence-Based Practice Capacity for TCM (No. 2019XZZX-XXG007), and the “Twelfth Five-Year” National Science and Technology Support Plan (No. 2013BAI02B02).

Conflict of interest

The authors declare no conflicts of interest.

Availability of data and material

The data used to support the findings of this study are available from the corresponding author upon request.

Code availability (software application or custom code)

Not applicable.

Author contributions

Boli Zhang and Jingyuan Mao were responsible for the conceptualization, funding acquisition, and project administration. Xianliang Wang and Zhiqiang Zhao were responsible for the entire research design process and finished the writing of original manuscript. All authors participated in patient recruitment and follow-up, and reviewed manuscript.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and the ethics committee of each participating research center (approval number: TYLL2015 [K] 004).

Consent to participate

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the

Consent for publication

Not applicable.

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Table 1 Baseline characteristics

Parameters	Treatment group (n = 317)	Control group (n = 322)	Statistics	P value
Demographic characteristics
Age (m ± SD years)	66.123 ± 8.895	66.040 ± 8.978	0.117	0.9070
Sex
Male [n (%)]	231 (72.87%)	233 (72.36%)	0.02	0.8850
Female [n (%)]	86 (27.13%)	89 (27.64%)	0.02	0.8850
Body weight (m ± SD kg)	68.749 ± 11.57	69.016 ± 12.128	0.283	0.7773
Height (m ± SD cm)	168.181 ± 7.402	167.923 ± 7.907	0.42	0.6747
Disease history
Course of coronary heart disease (m ± SD years)	6.331 ± 5.775	6.846 ± 6.394	1.067	0.2864
Course of HF (m ± SD years)	3.699 ± 3.949	3.931 ± 4.397	0.704	0.4820
Myocardial infarction [n (%)]	214 (67.51%)	222 (68.94%)	0.15	0.6966
Arrhythmia [n (%)]	111 (35.02%)	109 (33.85%)	0.10	0.7567
Hypertension [n (%)]	177 (55.84%)	180 (55.90%)	0.00	0.9869
Diabetes [n (%)]	138 (43.53%)	134 (41.61%)	0.24	0.6239
Hyperlipidemia [n (%)]	29 ( 9.15%)	39 (12.11%)	1.48	0.2245
Basic medication situation
Antiplatelet drugs [n (%)]	290 (91.48%)	296 (91.93%)	0.04	0.8392
Beta blockers [n (%)]	230 (72.56%)	239 (74.22%)	0.23	0.6332
Angiotensin converting enzyme inhibitors [n (%)]	109 (34.38%)	101 (31.37%)	0.66	0.4167
Angiotensin II receptor blockers [n (%)]	85 (26.81%)	105 (32.61%)	2.57	0.1091
Statins [n (%)]	283 (89.27%)	278 (86.34%)	1.29	0.2565
Nitrates [n (%)]	162 (51.10%)	173 (53.73%)	0.44	0.5069
Aldosterone receptor antagonists [n (%)]	247 (77.92%)	255 (79.19%)	0.15	0.6947
Diuretics [n (%)]	248 (78.23%)	250 (77.64%)	0.03	0.8564
Digoxin [n (%)]	92 (29.02%)	92 (28.57%)	0.02	0.8999
Clinical outcomes
BNP [Med (Q1,Q3) pg/ml]	850.0 (493.9,1630.0)	834.5 (471.0,1540.0)	0.079	0.9374
NYHA classification [n (%)]
Level Ⅲ	216 (68.14%)	224 (69.57%)	0.15	0.6970
Level Ⅳ	101 (31.86%)	98 (30.43%)	0.15	0.6970
LVEF (m ± SD %)	35.659 ± 7.657	35.648 ± 7.971	0.019	0.9851
MLHFQ Scoring (m ± SD)	74.528 ± 29.12	71.876 ± 28.592	1.161	0.2461
TCM four diagnosis information score (m ± SD)	40.949 ± 14.943	38.770 ± 14.647	1.86	0.0633

Table 2 Plasma BNP levels before and after treatment between the two groups [pg/ml, Med (Q1, Q3)]

Follow-up time	Treatment group (n = 317)	Control group (n = 322)	P value
Baseline	850.0 (493.9,1630.0)	834.5 (471.0,1540.0)	0.9374
8 days after enrollment	465.0 (187.0,893.0)	533.6 (256.0,1230.0)	0.0149
60 ± 3 days after enrollment	398.0 (145.0,786.0)	464.0 (195.0,1020.0)	0.0088

Table 3 NYHA cardiac function classification before and after treatment between the two groups [n (%)]

Croup	Follow-up time	NYHA I	NYHA II	NYHA III	NYHA IV
Treatment group (n = 317)	Baseline	0 (0.00%)	0 (0.00%)	216 (68.14%)	101 (31.86%)
	8 days after enrollment	14 ( 4.42%)	132 (41.64%)	147 (46.37%)	24 (7.57%)
	60 ± 3 days after enrollment	32 (10.09%	180 (56.78%)	83 (26.18%)	22 (6.94%)
Control group (n =3 22)	Baseline	0 (0.00%)	0 (0.00%)	224 (69.57%)	98 (30.43%)
	8 days after enrollment	4 ( 1.24%)	115 (35.71%)	159 (49.38%)	44 (13.66%)
	60 ± 3 days after enrollment	25 ( 7.76%)	144 (44.72%)	117 (36.34%)	36 (11.18%)

Table 4 LVEF, MLHFQ score, and TCM four diagnostic information score before and after treatment between the two groups (m ± SD)

Group	Follow-up time	LVEF (%)	MLHFQ scores
Treatment group (n = 317)	Baseline	35.659 ± 7.657	74.528 ± 29.12
Treatment group (n = 317)	60 ± 3 days after enrollment	41.872 ± 10.092^a)	44.373 ± 28.544^b)
Control group (n = 322)	Baseline	35.648 ± 7.971	71.876 ± 28.592
Control group (n = 322)	60 ± 3 days after enrollment	39.680 ± 10.158	49.916 ± 28.810

a)Compared with the control group, P < 0.01; b) Compared with the control group, P < 0.05.

Table 5 TCM four diagnostic information scores before and after treatment between the two groups (m ± SD)

Follow-up time	Treatment group (n = 317)	Control group (n = 322)	P value
Baseline	40.949 ± 14.94	38.770 ± 14.647	0.0633
8 days after enrollment	25.111 ± 13.249^b)	27.453 ± 14.004	0.0304
60 ± 3 days after enrollment	21.288 ± 12.634^a)	24.366 ± 14.371	0.0069

Table 6 Comparison of the incidence of adverse events between the two groups [n (%)]

Outcomes	Treatment group (n = 327)	Control group (n = 330)
All adverse events	18 (5.50%)	14 (4.24%)
Adverse events of interest
Respiratory disorders	3 (0.92%)	3 (0.91%)
Urinary disorders	4 (1.22%)	2 (0.61%)
Gastrointestinal disorders	2 (0.61%)	4 (1.21%)
Liver dysfunction	4 (1.22%)	2 (0.61%)
Renal function disorders	3 (0.92%)	3 (0.91%)
Other	1 (0.31%)	2 (0.61%)
Serious adverse events	1 (0.31%)	1 (0.30%)
Drug-related adverse reactions	2 (0.61%)	0 (0.00%)

Assessment of complementary treatment with Yiqi Fumai lyophilized injection on acute decompensated ischemic heart failure (ACT-ADIHF): a multicenter randomized controlled trial

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

1 Introduction

2 Methods

2.1 Study Design

2.2 Patient Screening Criteria

2.3 Randomization and Intervention

2.4 Outcomes

2.5 Sample Size Estimation

2.6 Statistical Analysis

3 Results

4 Discussion

5 Conclusion

Abbreviations

Declarations

References

Tables

Status:

Version 1