Efficacy and Safety of Yiqi Traditional Chinese Medicine Injections for Chronic Pulmonary Heart Disease: A Systematic Review With Pairwise Meta‐Analyses and Indirect Comparisons

Hongyi Yue; Jinxuan Chai; Hehe Liao; Yunfei Jia; Pingyi Wang

doi:10.1002/pul2.70333

. 2026 Jun 8;16(2):e70333. doi: 10.1002/pul2.70333

Efficacy and Safety of Yiqi Traditional Chinese Medicine Injections for Chronic Pulmonary Heart Disease: A Systematic Review With Pairwise Meta‐Analyses and Indirect Comparisons

Hongyi Yue ^1,², Jinxuan Chai ², Hehe Liao ¹, Yunfei Jia ¹, Pingyi Wang ^1,^3,^4,^✉

PMCID: PMC13244264 PMID: 42266818

ABSTRACT

In this study, we compared the clinical efficacy and safety of various Yiqi Chinese medicine injections in chronic pulmonary heart disease (CPHD) through pairwise meta‐analyses and indirect comparisons within a systematic review. We searched seven databases for randomized controlled trials (RCTs) of the protective effects of Yiqi Chinese medicine injections combined with standard care on CPHD. The literature search period extended from the establishment of the database to June 30, 2025. RevMan 5.4.1 and Stata 14.0 were used for quality assessment, pairwise meta‐analyses, and indirect comparisons. This study incorporated a total of 72 articles, which collectively involved 5836 patients and examined six distinct types of traditional Chinese medicine injections. The results indicated that the adjuvant conventional treatments of Shenfu, Shenmai, Huangqi, Shengmai, Xinmailong, and Shenqi Fuzheng injections were more effective than conventional treatment alone (p < 0.05) in enhancing clinical efficacy. Furthermore, based on limited evidence, Shenqi Fuzheng Injection may have potential benefits, but this finding is highly uncertain (surface under the cumulative ranking [SUCRA] = 79.7%). In addition, Shenqi Fuzheng injection also had a good effect on improving partial pressure of carbon dioxide (PaCO₂) (SUCRA = 81.9%) and partial pressure of oxygen (PaO₂) (SUCRA = 79.7%). On the basis of conventional treatment, the combination of the six traditional Chinese medicine injections mentioned above can significantly enhance the clinical efficacy rate. Compared with other injections, Shenqi Fuzheng injection may have benefits, but this finding is highly uncertain.

Keywords: Chinese medicine injections, chronic pulmonary heart disease, effectiveness, meta‐analysis, safety

1. Introduction

Chronic pulmonary heart disease (CPHD) is a condition characterized by the chronic impairment of lung function and structure. Long‐term damage to the lungs can result in pulmonary hypertension, which subsequently increases the workload on the right side of the heart and may ultimately lead to heart failure [1]. CPHD has a high incidence and a prolonged course, which poses a significant burden on public health and well‐being. Currently, conventional methods such as cardiotonics, diuretics, and vasodilators are commonly employed to treat CPHD in clinical practice. Although it alleviates patients' symptoms to a certain extent, it is challenging to effectively enhancing the body's immune and cardiopulmonary function, and it is easy to lead to the development of arrhythmia, electrolyte imbalances, and other toxic side effects [2, 3]. Traditional Chinese medicine provides unique benefits in the prevention and treatment of CPHD. When integrated with conventional Western medicine, it can reduce the dosage of Western medications, enhance therapeutic efficacy, and minimize the toxic side effects associated with Western drug therapies [4]. In recent years, traditional Chinese medicine injections have garnered significant attention from researchers as sterile preparations derived from herbal medicines, which can enhance the bioavailability and efficacy of herbal therapies [5].

In traditional Chinese medicine, CPHD should primarily be treated using methods that warm and tonify yang qi, and clear the heart and induce urination [6, 7]. Shenfu, Shenmai, Huangqi, Shengmai, Xinmailong, and Shenqi Fuzheng injections all possess the ability to Yiqi, Buyang and Lishui the body. They have been widely used as adjunct therapies in the treatment of patients with CPHD [4, 8]. Modern medicine holds that the core pathophysiology of CPHD involves hypoxia and carbon dioxide retention [9]. These factors trigger pulmonary vasoconstriction, spasm, and pulmonary inflammation, which in turn lead to increased blood viscosity [10]. These pathophysiological changes not only trigger mitochondrial dysfunction, driving structural remodeling of the pulmonary vasculature and creating a vicious cycle of “hypoxia‐inflammation‐metabolism‐remodeling,” but also ultimately lead to pulmonary arterial hypertension [11]. Therefore, Yiqi traditional Chinese medicine injections can interrupt this cycle, thereby reducing pulmonary vascular resistance and fundamentally improving the prognosis of CPHD. Researchers found that Huangqi Injection activates AMPK phosphorylation and inhibits mTOR, directly targeting metabolic reprogramming to counteract lipopolysaccharide‐induced inflammatory responses [12]. Shenfu Injection primarily focuses on inhibiting NF‐κB‐driven inflammation and TGF‐β‐driven fibrosis, directly intervening in vascular remodeling and the fibrotic process [13]. Shengmai Injections are characterized by their antioxidant properties that protect right ventricular function and ameliorate hypoxia/hemorheology, directly reducing the right ventricular workload and improving pulmonary circulation [14]. Xinmailong Injection alleviates pulmonary vascular resistance by restoring the balance of vasoactive substances through increasing nitric oxide and prostacyclin levels while simultaneously reducing endothelin levels [15].

However, it remains inconclusive which of the aforementioned injections demonstrates superior efficacy and safety. Therefore, we searched both Chinese and English databases for relevant literature. Subsequently, pairwise meta‐analyses and indirect comparisons were conducted to compare the clinical efficacy of the six traditional Chinese medicine injections regarding their effectiveness rates, cardiac function, and blood gas analysis in patients with CPHD. This analysis aimed to identify the most effective traditional Chinese medicine injections for treating CPHD and to provide evidence‐based medical support for clinical application.

2. Methods

This study was registered on the Prospective Registry for Systematic Reviews platform (PROSPERO), and any modifications can be found there. The registration number for this study on the PROSPERO platform is CRD42023461772. Furthermore, we finalized the project checklist in accordance with the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses 2020 statement (Supporting Information S1: File S1) [16].

2.1. Search Strategy

A search of the CNKI, WanFang, Cqvip, PubMed, SinoMed, Cochrane Library, and EMbase databases was conducted to collect six types of traditional Chinese medicine injections (Shenfu, Shenmai, Huangqi, Shengmai, Xinmailong, and Shenqi Fuzheng injections) for the treatment of CPHD. The time period for the literature search extends from the establishment of the database to June 30, 2025. In addition, to minimize the possibility of omission, we do not restrict the type of document, language, or subject of study during the initial stage. The construction of the literature search formula uses PubMed as an example, as illustrated in Figure 1. The search strategies for other databases are shown in Supporting Information S2: File S2.

2.2. Inclusion and Exclusion Criteria

According to the PICOS principle, the inclusion criteria are as follows [1]: Population: since diagnostic criteria for CPHD may vary by region or over time, the diagnosis must adhere to the standards established in the 2022 ESC/ERS guidelines or the 2018 Chinese guidelines. Although some included studies do not fully meet these criteria, the guidelines provide a standardized basis for study design and patient enrollment. In addition, both are consistent in the core diagnostic criteria for CPHD [17, 18] [2]. Intervention: in the experimental group, in addition to the treatments provided to the control group, Shenfu, Shenmai, Huangqi, Shengmai, Xinmailong, and ShenqiFuzheng injections were administered [3]. Comparison: the control group received conventional treatment, which included continuous low‐flow oxygen, diuretics, and vasodilators, as well as the correction of water and electrolyte imbalances and acid‐base imbalances [4]. Outcome: Outcome indicators included overall clinical efficacy, adverse effects, and relevant measures that directly or indirectly reflected cardiopulmonary function, such as left ventricular ejection fraction (LVEF), arterial blood partial pressure of carbon dioxide (PaCO₂), and partial pressure of oxygen (PaO₂). Adverse reactions are defined as any abnormal signs, symptoms, or laboratory values temporally linked to drug administration that necessitate discontinuation, dose reduction, or additional medical intervention [19] [5]. Study Design: randomized controlled trials (RCTs).

The exclusion criteria are as follows [1]: duplicate articles [2]; editorials, conference proceedings, abstracts, reviews, scientific reports, and dissertations [3]; studies that do not qualify as RCTs [4]; absence of intervention or control group models [5]; combination with other drugs [6]; incomplete data; and [7] lack of corresponding outcome measures.

2.3. Data Extraction

Two authors, Hongyi Yue and Jinxuan Chai, independently screened each study for inclusion and extracted relevant data. The details are as follows [1]: the name of the first author and the year of publication of the article [2]; the age, sample size, male‐to‐female ratio, and corresponding interventions for both the control and experimental groups [3]; the duration of treatment [4]; the randomization methods employed in the study; and [5] the outcome measures for each study. According to the established criteria, the overall response rate is classified into four levels: symptom control, apparent effect, effective, and ineffective. The total clinical effectiveness rate is calculated by summing the categories of apparent effect and effective to ensure accuracy.

2.4. Risk Assessment and Quality Evaluation

The quality assessment of the included studies was conducted using the Cochrane 5.3 Risk of Bias Assessment Tool [20]. The corresponding authors were responsible for verifying and correcting the original data. Furthermore, any disagreements that arose during the evaluation process were resolved by the corresponding authors. The main components of the assessment include: (A) a detailed description of the random sequence generation; (B) the adequacy of the concealment of the allocation sequence; (C) whether both participants and researchers were blinded; (D) whether the results were evaluated with the researchers blinded; (E) the completeness of the resulting data; (F) whether outcomes were reported selectively; and (G) other potential biases. In addition, outcome indicators were evaluated using the GRADE systematic rating methodology to assess their reliability and validity [21].

2.5. Statistical Analysis

Based on the frequentist statistical approach, RevMan 5.4.1 (The Cochrane Collaboration, London, England) and Stata/MP 14.0 (StataCorp, College Station, TX, USA) were utilized to generate the risk of bias plot and conduct pairwise meta‐analyses and indirect comparisons [22]. Indirect comparisons across injections were derived from their common comparator (conventional treatment), given the lack of head‐to‐head evidence. A p‐value of less than 0.05 was considered statistically significant. For dichotomous variables, the odds ratio (OR) was utilized as the measure of effect size. For continuous variables such as LVEF, PaCO₂, and PaO₂, the mean difference (MD) or standardized mean difference (SMD) was utilized as the effect size. By assuming a commutative correlation structure with proportional components in the mvmeta framework, the between‐study variance (τ ²) and I ² are measured to assess heterogeneity. The overall heterogeneity was quantified using the Cochrane Q statistic and the I ² index. Q follows a χ ² distribution with k − 1 degrees of freedom, where k represents the number of treatment comparisons relative to the reference treatment. I ² = (Q−df)/Q × 100% represents the percentage of total variation that can be attributed to real differences between studies rather than random error. A design‐by‐treatment interaction model assessed global network fit (Wald χ ² test, p > 0.05 indicates good fit). Subsequently, within the consistency framework, a leave‐one‐out sensitivity analysis was performed to evaluate the robustness of the outcomes. It is worth noting that because the included studies differed in age, sex, and units, all effect estimates are reported as SMDs [23]. The credibility interval (CI) was 95% for both data variables. We have calculated 95% CI for surface under the cumulative ranking (SUCRA) values using a bootstrap resampling approach (1000 iterations) to quantify the uncertainty in treatment rankings. The network evidence map is generated using the “network” command. When the network evidence graph forms a closed loop, the inconsistency model is applied for analysis. If no closed loop is present, the consistency model is utilized for analysis. The SUCRA is utilized to indicate the superiority of an intervention, with higher values reflecting greater efficacy of the intervention. Finally, we evaluated the included studies for publication bias by creating an adjusted funnel plot.

3. Results

3.1. Selection of Included Studies

A total of 1276 articles were identified from seven databases using the retrieval strategy. First, 855 duplicate articles were removed with NoteExpress software. The titles and abstracts of the remaining 421 articles were subsequently reviewed and screened by two authors, Hongyi Yue and Jinxuan Chai. Of these, 180 were unrelated to the research topic, 105 were mixed with other drugs, 12 reviews were excluded, 10 conference abstracts were excluded, 4 dissertations were excluded, and 3 scientific and technological achievement registration forms were also excluded from the study. Next, two authors conducted a comprehensive review of the remaining 106 articles, ultimately excluding 34. Of these, 21 were excluded because they were not RCTs; 11 lacked corresponding outcome measures; 1 was excluded because the intervention group did not meet the necessary criteria; and 2 were removed due to incomplete data. Finally, 72 articles were included in this meta‐analysis. The flow of the literature search is shown in Figure 2.

The process of literature search and screening.

3.2. Characteristics of the Included Studies

A total of 72 RCTs [24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95] involving 5836 patients with CPHD were included in this study, with 2931 participants in the experimental group and 2905 in the control group. The common age range is between 46 and 60 years, and the duration of treatment varies from 10 to 30 days. The included studies were all double‐arm clinical trials, in which the control group received conventional Western medicine, while the experimental group was treated with one of the six injections in addition to the control group's treatment. Among the studies, there are 13 publications on Shenfu Injection [28, 35, 45, 57, 58, 62, 64, 68, 71, 80, 87, 94, 95], 15 on Xinmailong Injection [33, 36, 39, 40, 48, 49, 52, 59, 63, 69, 85, 89, 91, 92, 93], 25 on Shenmai Injection [24, 25, 29, 31, 32, 37, 38, 42, 44, 46, 47, 53, 54, 55, 60, 65, 67, 74, 75, 79, 81, 82, 84, 86, 90], one on Shenqifuzheng Injection [66], 11 on Shengmai Injection [26, 34, 50, 51, 56, 70, 73, 76, 77, 78, 88], and seven on Huangqi Injection [27, 30, 41, 43, 61, 72, 83]. The fundamental characteristics of the included studies are presented in Table 1.

Table 1.

Basic characteristics of included articles.

Author and year	Stochastic methods	Control group		Experimental group			Duration of treatment (days)	Outcome measures
Author and year	Stochastic methods	Age	Sample size (male/female)	Age	Sample size (male/female)	Interventions	Duration of treatment (days)	Outcome measures
Hou 2012	D	56.00–87.00	39 (21/18)	59.00–89.00	39 (25/14)	Shenmai Injection	14	①
Ni 2013	D	65.95 ± 10.52	35 (22/13)	66.82 ± 10.31	35 (21/14)	Shenmai Injection	10	①⑤
Liu et al. 2010	D	67.00 ± 10.00	60 (45/15)	66.00 ± 9.00	60 (46/14)	Shengmai Injection	14	①
Liu 2012	D	49.00–75.00	15 (7/8)	49.00–75.00	15 (8/7)	Huangqi Injection	10	①
Liu et al. 2014	D	46.00–78.60	64 (39/25)	48.00–81.00	78 (51/27)	Shenfu Injection	14	①②
Liu et al. 2010	—	45.00–78.00	80 (38/42)	45.00–78.00	80 (31/49)	Shenmai Injection	15	①
Lu et al. 2014	D	62.00 ± 12.00	55 (31/24)	66.00 ± 11.00	60 (34/26)	Huangqi Injection	10–14	①③④⑤
Shi et al. 2013	D	52.00–70.00	45 (22/23)	52.00–70.00	45 (24/21)	Shenmai Injection	15	①③④
Shi et al. 2017	D	61.90 ± 10.70	40 (23/17)	62.60 ± 11.20	40 (21/19)	Shenmai Injection	14	①
Lv et al. 2019	D	63.00–81.00	92	63.00–81.00	92	Xinmailong Injection	10	①②
Tang 2018	D	65.30 ± 7.20	40 (24/16)	66.40 ± 7.10	40 (26/14)	Shengmai Injection	15	①③④
Tang et al. 2016	A	52.00–77.00	30	52.00–77.00	30	Shenfu Injection	14	①
Jiang et al. 2019	D	59.10 ± 5.90	50 (32/18)	58.20 ± 6.80	50 (28/22)	Xinmailong Injection	7	①②③④⑤
Sun 2013	D	52.00–84.00	20	52.00–84.00	23	Shenmai Injection	14	①
Yi 2011	—	58.00–82.00	20 (12/8)	58.00–82.00	20 (14/6)	Shenmai Injection	14	①⑤
Yue 2023	C	68.85 ± 5.21	26 (15/11)	67.49 ± 5.06	26 (16/10)	Xinmailong Injection	10	③④
Zhuang et al. 2016	D	55.00–80.00	34	55.00–80.00	34	Xinmailong Injection	7	①③④
Liao 2022	A	49.42 ± 2.15	39	49.39 ± 2.13	39	Huangqi Injection	—	①②③④
Liao 2011	—	58.00–82.00	20 (14/6)	58.00–82.00	20 (12/8)	Shenmai Injection	14	①⑤
Zhang et al. 2012	A	55.00–78.00	50	55.00–78.00	50	Huangqi Injection	14	①
Zhang 2010	D	48.00–80.00	60 (32/28)	48.00–80.00	60 (36/24)	Shenmai Injection	14	①⑤
Zhang et al.2023	A	67.00–82.80	24 (17/7)	79.30–84.80	24 (20/4)	Shenfu Injection	10	①③④⑤
Zhang 2011	D	58.00–82.00	20 (14/6)	58.00–82.00	20 (12/8)	Shenmai Injection	14	①⑤
Zhang 2012	C	65.80 ± 7.10	48 (29/19)	67.30 ± 6.20	48 (30/18)	Shenmai Injection	28	①⑤
Shi et al. 2015	D	59.10 ± 5.90	50 (30/20)	58.40 ± 6.80	50 (29/21)	Xinmailong Injection	7	①②⑤
Shi et al. 2016	C	60.30 ± 5.50	50 (29/21)	59.80 ± 5.30	50 (30/20)	Xinmailong Injection	7	①
Zhu et al. 2014	A	69.12 ± 5.71	84 (62/22)	71.32 ± 7.68	84 (68/16)	Shengmai Injection	14	①②
Li (a) 2011	D	59.60 ± 9.20	40 (24/16)	60.80 ± 9.00	40 (26/14)	Shengmai Injection	14	①
Li et al. 2020	D	65.00–82.00	57	65.00–82.00	57	Xinmailong Injection	10	②
Li 2020	A	52.11 ± 2.06	36 (21/15)	52.23 ± 2.18	36 (20/16)	Shenmai Injection	14	①
Li (b) 2011	D	57.00–80.00	46 (32/14)	55.00–81.00	46 (35/11)	Shenmai Injection	14	①
Li et al. 2012	D	69.00 ± 9.10	31 (17/14)	67.00 ± 8.30	30 (19/11)	Shenmai Injection	10	①③④⑤
Yang 2013	D	7.00–61.00	20	7.00–61.00	20	Shengmai Injection	28	③④
Wang et al. 2022	A	67.00 ± 17.00	50 (32/18)	69.00 ± 18.00	50 (33/17)	Shenfu Injection	14	①②③④
Shen et al. 2011	D	64.54 ± 8.13	42 (28/14)	68.32 ± 8.12	40 (30/10)	Shenfu Injection	10	①③④
Yan et al. 2019	D	64.80 ± 7.60	40 (25/15)	65.30 ± 8.90	40 (27/13)	Xinmailong Injection	14	①⑤
Wang 2011	D	40.00–82.00	56	40.00–82.00	56	Shenmai Injection	15	①
Wang et al. 2010	D	68.00	68 (36/32)	69.00	70 (36/34)	Shenfu Injection	14	①
Wang 2013	D	67.85 ± 11.15	40 (24/16)	66.50 ± 11.10	40 (23/17)	Huangqi Injection	14	①
Wang et al. 2012	D	70.54 ± 8.13	52 (32/20)	70.32 ± 8.12	50 (35/15)	Shenfu Injection	12	①③④
Wang 2018	D	72.13 ± 4.59	46 (25/21)	71.95 ± 4.63	46 (27/19)	Xinmailong Injection	10	②
Wang 2017	D	33.00–81.00	42 (28/14)	30.00–85.00	33 (29/13)	Shenfu Injection	14	①
Wang 2012	D	43.00–79.00	21	43.00–79.00	21	Shenmai Injection	14	①
Bai 2018	D	64.75 ± 11.06	41 (30/11)	65.18 ± 10.23	41 (27/14)	Shenqifuzheng Injection	14	①②③④
Yi 2011	D	55.00–79.00	34 (21/13)	52.00–83.00	41 (26/15)	Shenmai Injection	7	①
Tong et al. 2010	D	58.48 ± 5.38	40 (18/22)	56.80 ± 5.93	56 (36/20)	Shenfu Injection	30	①②
Luo et al. 2013	D	56.00–80.00	30	56.00–80.00	30	Xinmailong Injection	10	①②③④
Xiao 2014	D	54.00–81.00	39 (20/19)	56.00–83.00	39 (21/18)	Shengmai Injection	7–10	①
Hu et al. 2015	A	61.80 ± 13.70	34 (18/16)	62.40 ± 13.60	34 (20/14)	Shenfu Injection	15	①②
Shu 2014	D	66.65 ± 10.11	50 (24/26)	65.60 ± 10.10	50 (23/27)	Huangqi Injection	14	①③④
Miao 2011	—	52.00–80.00	20 (15/5)	50.00–81.00	20 (16/4)	Shengmai Injection	7–10	①
Fan 2016	D	60.00–71.00	19 (15/4)	62.00–73.00	19 (16/3)	Shenmai Injection	15	①⑤
Qin 2017	C	47.60 ± 3.50	15 (7/8)	48.00 ± 3.70	15 (8/7)	Shenmai Injection	14	①
Xu 2018	D	72.95 ± 5.44	82 (61/21)	72.68 ± 5.35	82 (62/20)	Shengmai Injection	14	①
Xie et al. 2013	D	7.00–61.00	20	7.00–61.00	20	Shengmai Injection	28	③④
Zhao 2013	D	—	30	—	30	Shengmai Injection	14	①
Zhao 2011	D	64.45 ± 9.85	40 (19/21)	69.15 ± 11.00	40 (20/20)	Shenmai Injection	14	①③④
Zhao et al. 2011	D	63.20 ± 4.90	46 (25/21)	64.40 ± 5.10	46 (26/20)	Shenfu Injection	14	①②⑤
Wu 2011	D	43.00–79.00	21	43.00–79.00	21	Shenmai Injection	14	①③④
Zou et al. 2011	D	60.08 ± 4.78	27 (13/14)	59.49 ± 4.56	27 (17/10)	Shenmai Injection	7 or 14	①⑤
Zou 2016	B	65.00–77.00	20 (20/0)	65.00–77.00	20 (20/0)	Huangqi Injection	10	①
Zheng 2011	D	43.00–79.00	21	43.00–79.00	21	Shenmai Injection	14	①③④
Jin et al. 2021	D	71.30 ± 5.10	40 (33/7)	70.90 ± 6.40	41 (32/9)	Xinmailong Injection	5	②
Jin 2010	—	58.00–82.00	20 (12/8)	58.00–82.00	20 (14/6)	Shenmai Injection	14	①⑤
Qian 2015	A	68.50 ± 2.90	33 (19/14)	71.20 ± 3.40	33 (20/13)	Shenfu Injection	14	①
Chen 2010	D	45.00–79.00	50 (23/27)	48.00–79.00	50 (24/26)	Shengmai Injection	14	①③④⑤
Chen et al. 2022	A	67.56 ± 5.88	40 (23/17)	67.76 ± 5.44	40 (22/18)	Xinmailong Injection	5	①②
Jin 2012	A	57.20 ± 9.10	60 (37/23)	56.30 ± 8.60	60 (39/21)	Shenmai Injection	14	②
Han et al. 2019	A	—	50	—	50	Xinmailong Injection	10	①⑤
Ma et al. 2014	A	52.00–84.00	37	52.00–84.00	37	Xinmailong Injection	10	①②③④⑤
Huang 2016	D	72.60 ± 2.50	34 (19/15)	72.90 ± 2.40	34 (20/14)	Xinmailong Injection	10	①②
Huang et al. 2013	D	55.00–75.00	35	55.00–75.00	35	Shenfu Injection	14	②

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Note: Age, expressed as an average or within a specified range. A, random number table method; B, random blinding; C, grouped according to their preferences; D, only mention randomness. —, Not reported. ①, The overall response rate; ②, Left ventricular ejection fraction; ③, Partial pressure of carbon dioxide; ④, Partial pressure of oxygen; ⑤, Adverse reaction.

3.3. Quality Assessment of Included Studies

In terms of the randomization of study sequences, 13 studies utilized random number tables [35, 41, 43, 45, 50, 53, 57, 71, 87, 89, 90, 91, 92], one employed double‐blind randomization methods [83], and 49 studies mentioned randomization without specifying the methods used [24, 25, 26, 27, 28, 30, 31, 32, 33, 34, 36, 37, 40, 44, 46, 48, 51, 52, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 72, 74, 76, 77, 78, 79, 80, 81, 82, 84, 85, 88, 93, 94, 95]. These studies were assessed as having a low risk of bias. Five studies were classified as having an unclear risk because they did not specify the randomization method used [29, 38, 42, 73, 86], while four studies were rated as high risk due to being grouped based on participants' preferences [39, 47, 49, 75]. In terms of allocation concealment for study sequences, only one paper described the allocation concealment scheme, which was rated as low risk [45]. The remaining studies did not report this information and were rated as having unclear risk. In terms of blinding for both researchers and participants, two studies reported successful blinding and were rated as having a low risk of bias [45, 83]. Four studies were classified as high risk due to the use of inappropriate methods for random sequence generation [39, 47, 49, 75]. The remaining studies are not described in detail and are categorized as having unclear risks. In terms of the completeness of results, the studies either had relatively comprehensive data or provided detailed reports on the causes of shedding; therefore, they were all rated as low risk. In addition, none of the studies were blinded to outcomes, selectively reported results, or exhibited any other biases; therefore, they were rated as having an unclear risk of bias. The risk of bias in the included studies is assessed in Figure 3.

Risk of bias profiles of included studies.

3.4. Quality Evaluation of Outcome Indicators

Using the GRADE rating methodology, this study comprehensively evaluates each outcome indicator. The results showed (Supporting Information S3: File S3) that the proportion of outcome indicators of moderate quality was 20.24% (17/84), the proportion of outcome indicators of low quality was 54.76% (46/84), and the proportion of outcome indicators of very low quality was 25.00% (21/84). The primary reasons for downgrading the quality of the evidence were the risk of bias and publication bias. Additionally, we downgraded the quality of the results due to the limited data available for certain outcomes.

3.5. Clinical Efficacy

Improvement in CPHD was reported in 64 studies involving 5227 patients [24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 53, 54, 55, 57, 58, 59, 60, 61, 62, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 78, 79, 80, 81, 82, 83, 84, 86, 87, 88, 89, 91, 92, 93, 95]. This comparison included six traditional Chinese medicine injections, leading to six direct comparisons. Due to the lack of a closed loop, we utilized a consistency model for the analysis. The network relationships are illustrated in Figure 4A, where the size of the dots represents the sample size of various interventions, and the thickness of the lines indicates the volume of literature.

(A) Evidence network of the effectiveness of different Chinese medicine injections in improving CPHD. (B) SUCRA probability ranking plot of the clinical treatment effect of different traditional Chinese medicine injections in improving CPHD. (C) Direct comparison forest plot: clinical efficacy of six Yiqi injections versus conventional treatment.

The results of the probability ranking chart indicated that the clinical treatment effect of Shenqi Fuzheng Injection may be the most effective, followed by Xinmailong Injection. The order of improvement in the clinical effective rate was as follows: Shenqi Fuzheng Injection (SUCRA = 79.7%, 95% CI: 16.67%–100.00%) > Xinmailong Injection (SUCRA = 73.3%, 95% CI: 33.33%–100.00%) > Shenfu Injection (SUCRA = 65.2%, 95% CI: 33.33%–100.00%) > Shenmai Injection (SUCRA = 61.7%, 95% CI: 33.33%–100.00%) > Huangqi Injection (SUCRA = 47.6%, 95% CI: 16.67%–100.00%) > Shengmai Injection (SUCRA = 22.3%, 95% CI: 16.67%–50.00%) > conventional treatment (SUCRA = 0.2%, 95% CI: 0.00%–0.00%). For further details, please refer to Figure 4B.

For this outcome indicator, a total of 21 direct or indirect comparisons were identified, 7 of which were statistically significant. When compared to conventional treatment, the following interventions demonstrated improved clinical efficacy for CPHD (p < 0.05): Shenqi Fuzheng Injection [OR = 6.29, 95% CI: (1.23, 32.28)], Xinmailong Injection [OR = 4.26, 95% CI: (2.73, 6.64)], Shenfu Injection [OR = 3.89, 95% CI: (2.70, 5.60)], Shenmai Injection [OR = 3.78, 95% CI: (2.73, 5.22)], Huangqi Injection [OR = 3.22, 95% CI: (1.98, 5.23)], and Shengmai Injection [OR = 2.23, 95% CI: (1.41, 3.53)]. In addition, the comparison of traditional Chinese medicine injections indicated that Xinmailong Injection was more effective than Shengmai Injection in enhancing clinical outcomes [OR = 1.91, 95% CI: (1.01, 3.61)], with a statistically significant difference (p < 0.05). The results of the analysis are presented in Table 2. The results of direct comparisons also suggest that, compared with conventional treatment, all six Yiqi traditional Chinese medicine injections show significant clinical efficacy (Figure 4C).

Table 2.

Pairwise meta‐analyses and indirect comparisons of clinical efficacy and LVEF.

Clinical efficacy [OR (95% CI)] and LVEF [SMD (95% CI)]
Shenqi Fuzheng Injection	Conventional treatment	−0.44 (−10.41, 9.52)	−0.46 (−10.43, 9.50)	0.90 (−3.17, 4.97)	2.01 (−7.96, 11.99)	2.02 (−7.95, 11.99)	5.19 (1.99, 8.38)*
1.48 (0.27, 8.05)	Xinmailong Injection	Shenmai Injection	−0.02 (−14.11, 14.07)	1.35 (−9.42, 12.11)	2.46 (−11.64, 16.55)	2.47 (−11.63, 16.56)	5.63 (−4.83, 16.09)
1.62 (0.30, 8.65)	1.10 (0.62, 1.95)	Shenfu Injection	Shengmai Injection	1.37 (−9.39, 12.13)	2.48 (−11.62, 16.57)	2.49 (−11.61, 16.58)	5.65 (−4.81, 16.11)
1.67 (0.31, 8.83)	1.13 (0.65, 1.96)	1.03 (0.63, 1.68)	Shenmai Injection	Shenfu Injection	1.11 (−9.66, 11.88)	1.12 (−9.65, 11.89)	4.28 (−0.89, 9.46)
1.95 (0.35, 10.76)	1.32 (0.68, 2.55)	1.21 (0.66, 2.22)	1.17 (0.65, 2.10)	Huangqi Injection	Huangqi Injection	0.01 (−14.09, 14.11)	3.17 (−7.30, 13.64)
2.82 (0.52, 15.42)	1.91 (1.01, 3.61)*	1.74 (0.98, 3.11)	1.69 (0.97, 2.96)	1.44 (0.74, 2.81)	Shengmai Injection	Shenqi Fuzheng Injection	3.16 (−7.31, 13.63)
6.29 (1.23, 32.28)*	4.26 (2.73, 6.64)*	3.89 (2.70, 5.60)*	3.78 (2.73, 5.22)*	3.22 (1.98, 5.23)*	2.23 (1.41, 3.53)*	Conventional treatment	Xinmailong Injection

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Note: *p < 0.05. Different Chinese medicine injections improve the clinical effective rate (lower left corner) and LVEF (upper right corner).

3.6. LVEF

Improvement in LVEF was reported in 20 studies involving 1953 individuals with CPHD [28, 33, 36, 41, 48, 50, 52, 57, 63, 66, 68, 69, 71, 80, 85, 89, 90, 92, 93, 94]. The six traditional Chinese medicine injections mentioned above were all included in the analysis. Since no closed loop was formed, a consistency model was employed for evaluation. The mesh diagram is presented in Figure 5A.

(A) Evidence network for Chinese medicine injections to improve LVEF. (B) SUCRA probability ranking plot of the LVEF of different traditional Chinese medicine injections in improving CPHD. (C) Direct comparison forest plot: LVEF of six Yiqi injections versus conventional treatment.

The results of the probability ranking chart indicated that Xinmailong injection was the most effective drug regimen for increasing the level of LVEF, followed by Shenqi Fuzheng injection and Huangqi Injection. The order of SUCRA was as follows: Xinmailong Injection (SUCRA = 85.2%, 95% CI: 50.00%–100.00%) > Shenqi Fuzheng Injection (SUCRA = 55.0%, 95% CI: 0.00%–100.00%) > Huangqi Injection (SUCRA = 55.0%, 95% CI: 0.00%–100.00%) > Shenfu Injection (SUCRA = 46.0%, 95% CI: 0.00%–83.33%) > Shengmai Injection (SUCRA = 37.0%, 95% CI: 0.00%–100.00%) > Shenmai Injection (SUCRA = 36.9%, 95% CI: 0.00%–100.00%) > conventional treatment (SUCRA = 34.9%, 95% CI: 0.00%–66.67%). See Figure 5B.

Analysis of this outcome indicator shows that, compared with conventional treatment alone, only Xinmailong injection [SMD = 4.26, 95% CI: (2.73, 6.64)] significantly improved LVEF levels. This result is also indicated by direct comparison (Figure 5C). The comparison of Yiqi traditional Chinese medicine injections indicated that there was no significant effect on the improvement of LVEF (p > 0.05). The specific results are presented in Table 2.

3.7. PaCO₂ and PaO₂

Twenty‐one studies [30, 31, 34, 36, 39, 40, 41, 45, 55, 56, 57, 58, 62, 66, 69, 72, 77, 79, 81, 84, 92] reported improvements in both PaCO₂ and PaO₂ levels. Both indicators involved six types of Yiqi traditional Chinese medicine injections, leading to six direct comparisons. Furthermore, neither of the indicators forms a closed loop. See Figure 6A,B for details.

Evidence network for the improvement of PaCO₂ (A) and PaO₂ (B) by different traditional Chinese medicine injections. SUCRA probability ranking plot of different traditional Chinese medicine injections to improve PaCO₂ (C) and PaO₂ (D).

The SUCRA ranking for Yiqi traditional Chinese medicine injections in improving PaCO₂ was as follows: Shenqi Fuzheng Injection (SUCRA = 81.9%, 95% CI: 16.67%–100.00%) > Shenfu Injection (SUCRA = 70.9%, 95% CI: 16.67%–100.00%) > Xinmailong Injection (SUCRA = 65.6%, 95% CI: 16.67%–100.00%) > Shenmai Injection (SUCRA = 63.5%, 95% CI: 16.67%–100.00%) > conventional treatment (SUCRA = 35.7%, 95% CI: 16.67%–66.67%) > Shengmai Injection (SUCRA = 28.5%, 95% CI: 0.00%–83.33%) > Huangqi Injection (SUCRA = 4.0%, 95% CI: 0.00%–33.33%). Refer to Figure 6C. The SUCRA ranking for Yiqi traditional Chinese medicine injections in improving PaO₂ was as follows: Shenqi Fuzheng Injection (SUCRA = 93.8%, 95% CI: 33.33%–100.00%) > Shenfu Injection (SUCRA = 67.1%, 95% CI: 16.67%–100.00%) > Shenmai Injection (SUCRA = 53.8%, 95% CI: 16.67%–100.00%) > Xinmailong Injection (SUCRA = 51.8%, 95% CI: 16.67%–83.33%) > Shengmai Injection (SUCRA = 49.0%, 95% CI: 0.00%–100.00%) > conventional treatment (SUCRA = 32.4%, 95% CI: 16.67%–66.67%) > Huangqi Injection (SUCRA = 2.1%, 95% CI: 0.00%–16.67%) (see Figure 6D).

The analysis results indicate that, compared with conventional treatment alone, tonic Chinese medicine injections did not significantly improve PaCO₂ or PaO₂ levels (p > 0.05). This result is also indicated by direct comparison (Figure 7). The comparison of Chinese medicine injections showed that Shenqi Fuzheng Injection [SMD = −4.28, 95% CI: (−8.50, −6.64)], Shenfu Injection [SMD = −3.25, 95% CI: (−6.05, −0.45)], Xinmailong Injection [SMD = −3.04, 95% CI: (−5.72, −0.35)], and Shenmai Injection [SMD = −2.92, 95% CI: (−5.60, −0.24)] were more effective than Huangqi Injection in improving PaCO₂ in CPHD patients (p < 0.05). In addition, Shenqi Fuzheng Injection [SMD = 8.47, 95% CI: (2.21, 14.73)] was significantly more effective than Huangqi Injection (p < 0.05) in improving PaO₂ indices (see Table 3).

Direct comparison forest plot: PaCO₂ (A) and PaO₂ (B) of six Yiqi injections versus conventional treatment.

Table 3.

Pairwise meta‐analyses and indirect comparisons of PaCO₂ and PaO₂.

PaCO₂ [SMD (95% CI)] and PaO₂ [SMD (95% CI)]
Shenqi Fuzheng Injection	Huangqi Injection	3.23 (0.07, 6.40)	3.93 (−0.49, 8.36)	4.02 (0.05, 7.98)	4.17 (0.20, 8.14)	4.90 (0.76, 9.05)	8.47 (2.21, 14.73)*
−1.03 (−5.10, 3.04)	Shenfu Injection	Conventional treatment	0.70 (−2.39, 3.79)	0.78 (−1.61, 3.17)	0.94 (−1.46, 3.33)	1.67 (−1.00, 4.35)	5.24 (−0.16, 10.64)
−1.24 (−5.23, 2.75)	−0.21 (−2.65, 2.22)	Xinmailong Injection	Shengmai Injection	0.08 (−3.83, 3.99)	0.24 (−3.67, 4.14)	0.97 (−3.12, 5.06)	4.54 (−1.69, 10.76)
−1.35 (−5.34, 2.63)	−0.33 (−2.77, 2.11)	−0.11 (−2.42, 2.19)	Shenmai Injection	Xinmailong Injection	0.15 (−3.23, 3.54)	0.89 (−2.70, 4.48)	4.46 (−1.45, 10.36)
−2.21 (−5.85, 1.44)	−1.18 (−3.00, 0.64)	−0.97 (−2.59, 0.66)	−0.85 (−2.48, 0.78)	Conventional treatment	Shenmai Injection	0.73 (−2.85, 4.32)	4.30 (−1.61, 10.21)
−2.70 (−6.91, 1.52)	−1.67 (−4.46, 1.12)	−1.46 (−4.13, 1.21)	−1.34 (−4.01, 1.33)	−0.49 (−2.61, 1.63)	Shengmai Injection	Shenfu Injection	3.57 (−2.46, 9.60)
−4.28 (−8.50, −0.06)*	−3.25 (−6.05, −0.45)*	−3.04 (−5.72, −0.35)*	−2.92 (−5.60, −0.24)*	−2.07 (−4.20, 0.06)	−1.58 (−4.58, 1.42)	Huangqi Injection	Shenqi Fuzheng Injection

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Note: *p < 0.05. Different Chinese medicine injections improve the PaCO₂ (lower left corner) and PaO₂ (upper right corner).

3.8. The SUCRA Rankings Without Shenqi Fuzheng Injection

To assess the impact of Shenqi Fuzheng Injection on overall treatment ranking, we conducted a secondary SUCRA analysis, excluding Shenqi Fuzheng Injection from the evidence network. The SUCRA rankings after excluding Shenqi Fuzheng Injection are as follows.

Clinical Efficacy: Xinmailong Injection (SUCRA = 82.1%, 95% CI: 40.00%–100.00%) > Shenfu Injection (SUCRA = 72.26%, 95% CI: 40.00%–100.00%) > Shenmai Injection (SUCRA = 70.18%, 95% CI: 40.00%–100.00%) > Huangqi Injection (SUCRA = 57.18%, 95% CI: 20.00%–100.00%) > Shengmai Injection (SUCRA = 23.68%, 95% CI: 20.00%–40.00%) > conventional treatment (SUCRA = 0.0%, 95% CI: 0.00%–0.00%). For further details, please refer to Figure 8A.

The SUCRA probability ranking diagram of different traditional Chinese medicine injections after excluding Shenqi Fuzheng injection. (A) Clinically effective, (B) LVEF, (C) PaCO₂, (D) PaO₂.

LVEF: Xinmailong Injection (SUCRA = 96.44%, 95% CI: 80.00%–100.00%) > Huangqi Injection (SUCRA = 83.56%, 95% CI: 80.00%–100.00%) > Shenfu Injection (SUCRA = 60.00%, 95% CI: 60.00%–60.00%) > conventional treatment (SUCRA = 39.72%, 95% CI: 40.00%–40.00%) > Shenmai Injection (SUCRA = 11.16%, 95% CI: 00.00%–20.00%) > Shengmai Injection (SUCRA = 9.12%, 95% CI: 00.00%–20.00%). For further details, please refer to Figure 8B.

PaCO₂: Shenfu Injection (SUCRA = 99.58%, 95% CI: 100.0%–100.0%) > Shenmai Injection (SUCRA = 70.22%, 95% CI: 60.00%–80.00%) > Xinmailong Injection (SUCRA = 69.96%, 95% CI: 60.00%–80.00%) > Shengmai Injection (SUCRA = 37.30%, 95% CI: 00.00%–40.00%) > Huangqi Injection (SUCRA = 15.84%, 95% CI: 0.00%–40.00%) > conventional treatment (SUCRA = 7.10%, 95% CI: 0.00%–20.00%). For further details, please refer to Figure 8C.

PaO₂: Shenfu Injection (SUCRA = 100.00%, 95% CI: 100.0%–100.0%) > Shenmai Injection (SUCRA = 74.66%, 95% CI: 40.00%–80.00%) > Shengmai Injection (SUCRA = 47.96%, 95% CI: 20.00%–80.00%) > Xinmailong Injection (SUCRA = 42.14%, 95% CI: 20.00%–80.00%) > Huangqi Injection (SUCRA = 35.24%, 95% CI: 20.00%–80.00%) > conventional treatment (SUCRA = 0.00%, 95% CI: 0.00%–0.00%). For further details, please refer to Figure 8D.

3.9. Detection of Publication Bias

Funnel plots were generated for clinical effectiveness, LVEF, PaCO₂, and PaO₂ outcomes. The results demonstrated poor symmetry, with some studies deviating significantly from the regression line, suggesting the possibility of publication bias (see Figure 9).

Funnel plot for comparison‐correction. (A) Clinically effective, (B) LVEF, (C) PaCO₂, (D) PaO₂.

3.10. Heterogeneity Tests

The heterogeneity test for the clinical efficacy rate outcome revealed significant heterogeneity between Shengmai Injection and conventional treatment (I ² = 64%, τ ² = 0.67). The heterogeneity test for LVEF revealed heterogeneity in the comparisons between Xinmailong Injection and conventional treatment (I ² = 97.7%, τ ² = 3.88) and between Shenfu Injection and conventional treatment (I ² = 57.1%, τ ² = 0.07). The heterogeneity test for PaCO₂ revealed heterogeneity in the comparisons between Shenmai Injection and conventional treatment (I ² = 88.0%, τ ² = 0.55), Xinmailong Injection versus conventional treatment (I ² = 96.9%, τ ² = 3.43), Shengmai Injection versus conventional treatment (I ² = 98.7%, τ ² = 5.19), and Huangqi Injection versus conventional treatment (I ² = 77.1%, τ ² = 0.22). The heterogeneity test results for PaO₂ showed significant heterogeneity in the following comparisons: Shenfu Injection versus conventional treatment (I ² = 94.1%, τ ² = 1.22), Shenmai Injection versus conventional treatment (I ² = 89.4%, τ ² = 0.65), Xinmailong Injection versus conventional treatment (I ² = 61.8%, τ ² = 0.10), and Huangqi Injection versus conventional treatment (I ² = 98.8%, τ ² = 6.23). Heterogeneity was generally low or limited to a single study in the remaining comparisons.

3.11. Meta‐Regression Analysis

To investigate the sources of heterogeneity, we conducted a meta‐regression analysis. The results are presented in Supporting Information S4: File S4. The analysis revealed that most covariates were not sources of heterogeneity. However, when analyzing PaCO₂ and PaO₂ outcomes, CPHD severity was identified as a source of heterogeneity for Xinmailong Injection.

3.12. Overall Model Fit and Leave‐One‐Out Robustness

The network evidence diagram shows that no closed loops were formed for any outcome indicators, precluding an inconsistency test. Therefore, this study used a consistency model for analysis. The overall heterogeneity of the clinical effective rate outcome was low (Q = 5.58, df = 5, I ² = 10.00%); the Wald test indicated significant overall inconsistency (χ ² = 22.27, df = 1, p < 0.001). For LVEF, heterogeneity was also low (Q = 3.82, df = 5, I ² = 0%) with no significant inconsistency (χ ² = 0.16, df = 1, p = 0.69 > 0.001). For PaCO₂, heterogeneity was low (Q = 8.25, df = 5, I ² = 39.41%) with no significant inconsistency (χ ² = 3.62, df = 1, p = 0.06 > 0.001). For PaO₂, heterogeneity was low (Q = 9.19, df = 5, I ² = 45.59%) with no significant inconsistency (χ ² = 4.01, df = 1, p = 0.05 > 0.001). Leave‐one‐out analysis showed that no single study decisively impacted pooled estimates for any outcome, and excluding individual studies did not change statistical significance (Figure 10). The impact of individual studies on pooled effect estimates in meta‐analysis is detailed in Supporting Information S5: File S5.

Leave‐one‐out sensitivity analysis. (A) Clinically effective, (B) LVEF, (C) PaCO₂, (D) PaO₂.

3.13. Adverse Reactions

Nineteen studies [25, 30, 36, 38, 42, 44, 45, 46, 47, 48, 55, 59, 74, 80, 82, 86, 88, 91, 92] mentioned adverse effects, but only 12 reported specific adverse events. Among these, no adverse reactions were reported for either Shenqi Fuzheng Injection or Huangqi Injection. The most common adverse reactions included dry cough, diarrhea, rash, nausea, and headache. Based on the results, Shenqi Fuzheng Injection and Huangqi Injection demonstrated better safety profiles compared to other Yiqi injections.

4. Discussion

Modern medicine holds that chronic obstructive emphysema is the primary cause of CPHD, and supplement qi and nourish yin play a significant role in determining its outcome [96]. However, there are many types of Yiqi traditional Chinese medicine injections, and no studies have compared the protective effects of these tonic injections on CPHD. As a result, clinicians face challenges in selecting the most appropriate treatment. This study employed pairwise meta‐analyses and indirect comparisons to compare the efficacy of various Yiqi traditional Chinese medicine injections in treating CPHD across multiple outcome indicators. The treatments were ranked using the SUCRA, offering valuable guidance for clinical practice.

This study comprehensively evaluated 72 RCTs, including 5836 CPHD patients. The results demonstrated that Shenfu, Shenmai, Huangqi, Shengmai, Xinmailong, and Shenqi Fuzheng injections, when combined with conventional treatment, significantly improved clinical efficacy compared to conventional treatment alone. The SUCRA analysis indicated that, in terms of improving clinical efficiency, PaCO₂, and PaO₂, Shenqi Fuzheng Injection demonstrated the highest efficacy. For improving LVEF, Xinmailong Injection showed the greatest efficacy, followed by Shenqi Fuzheng and Huangqi Injections. In terms of safety, Shenqi Fuzheng Injection and Huangqi Injection are safer than other Yiqi traditional Chinese medicine injections. However, it should be noted that the high ranking of Shenqi Fuzheng Injection is based solely on limited direct evidence (one RCT involving 82 patients), and the confidence interval for the SUCRA score is wide, which casts doubt on the reliability of this injection as the optimal adjunctive treatment option.

To address this issue, we conducted a leave‐one‐out sensitivity analysis and a reanalysis of the SUCRA data excluding Shenqi Fuzheng Injection. After excluding Shenqi Fuzheng Injection from the analysis, highest SUCRA rankings for clinical efficacy and LVEF outcomes shifted to Xinmailong Injection. Although the relative ordering of the remaining interventions remained largely consistent with the primary analysis, the 95% confidence intervals for the top‐ranked treatments were wide and mutually overlapping. This indicates that even in the absence of Shenqi Fuzheng Injection, the certainty of identifying a single “best” intervention remains low. Therefore, we have refrained from declaring any intervention as definitively optimal and instead present the results as a probabilistic ranking with associated uncertainty. Notably, SUCRA rankings remain relatively stable regardless of whether Shenqi Fuzheng Injection is included or excluded. Combined with the sensitivity analysis using the “leave‐one‐out” method, this further demonstrates the robustness of our analysis. In addition, to explore potential sources, we performed meta‐regression using treatment duration, sample size, CPHD severity (with vs. without heart failure), and guideline version as covariates. Most of these covariates did not provide a significant explanation for heterogeneity. Due to insufficient reporting details in the original studies, we were unable to assess differences in standard treatment regimens or acute exacerbations. This persistent heterogeneity likely stems from inherent diversity in traditional Chinese medicine injection trials and underscores the need for more standardized trial design and comprehensive reporting in future research.

Shenqii Fuzheng Injection is derived from a combination of traditional Chinese medicinal herbs, including Codonopsis Pilosula and Astragalus Membranaceus. It is an effective remedy for tonify qi [97]. Modern pharmacology has found that Codonopsis Pilosula and Astragalus Membranaceus, the components of Shenqi Fuzheng Injection, possess antioxidant and free radical scavenging properties, exhibit anti‐infective effects, and improve microcirculation [98]. The polysaccharides found in Astragalus Membranaceus and Codonopsis Pilosula play a crucial role in immunomodulation and can improve the overall nutritional status of patients [99]. In addition, based on the clear role of AMPK in maintaining mitochondrial homeostasis, and the obvious dysregulation of the AMPK/mTOR pathway during hypoxic pulmonary vascular remodeling, we speculate that Shenqi Fuzheng Injection may regulate mitochondrial homeostasis in pulmonary vascular endothelial cells through this pathway, thereby playing an important role in the treatment of CPHD [100, 101]. These effects, encompassing immune regulation and metabolic repair, provide a solid pharmacological basis for the application of Shenqi Fuzheng Injection in the treatment of CPHD.

4.1. Strengths and Limitations

This study conducted pairwise meta‐analyses and indirect comparisons to evaluate the adjuvant treatment effects of Yiqi traditional Chinese medicine injections on CPHD. Although this study incorporated an extensive body of literature, certain limitations persist. First, all included RCTs were conducted in China, which limits the generalizability of our findings. Second, the quality of the included studies is low, as most failed to report critical details such as allocation concealment. Third, there are no direct comparisons between different Yiqi traditional Chinese medicine injections, which may affect the reliability of the results. Fourth, the original studies did not provide sufficiently detailed data on patient‐centered hard‐endpoint measures (mortality, readmission rates, and quality of life), which limits the precision of our clinical conclusions. Finally, Shenqi Fuzheng Injection is represented in only one study, increasing the variability and uncertainty of the findings.

5. Conclusion

Based on limited evidence, compared with the other five injections, Shenqi Fuzheng Injection combined with conventional drugs in the treatment of CPHD may have benefits, but this finding is highly uncertain. More high‐quality, large‐sample RCTs are needed to verify its efficacy more clearly.

Author Contributions

Hongyi Yue and Hehe Liao: conception, study design, execution, data acquisition, analysis, and interpretation. Jinxuan Chai and Yunfei Jia: studies search, data collection. Pingyi Wang: design and funds collection. All Authors contributed to this study and approved the submitted version.

Disclosure

Pingyi Wang is the guarantor of this work and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Ethics Statement

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Supporting File 1

PUL2-16-e70333-s002.docx^{(29.8KB, docx)}

Supporting File 2

PUL2-16-e70333-s001.docx^{(1.1MB, docx)}

Supporting File 3

PUL2-16-e70333-s004.docx^{(34.6KB, docx)}

Supporting File 4

PUL2-16-e70333-s003.docx^{(24.1KB, docx)}

Supporting File 5

PUL2-16-e70333-s005.docx^{(37.9KB, docx)}

Acknowledgments

This study was financially supported by the Scientific Research Project of Xizang Minzu University (No. 23MDQ02), the Shaanxi Provincial Department of Education General Special Scientific Research Program Project (Nos. 24JK0687 and 24JK0688), the Natural Science Foundation Project of Tibet Autonomous Region (No. XZ202501ZR0034), the Scientific Research Project of Xizang Minzu University (No. 25MD10), the Hainan Provincial Natural Science Foundation Project (No. 826QN0874).

Data Availability Statement

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

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supporting File 1

PUL2-16-e70333-s002.docx^{(29.8KB, docx)}

Supporting File 2

PUL2-16-e70333-s001.docx^{(1.1MB, docx)}

Supporting File 3

PUL2-16-e70333-s004.docx^{(34.6KB, docx)}

Supporting File 4

PUL2-16-e70333-s003.docx^{(24.1KB, docx)}

Supporting File 5

PUL2-16-e70333-s005.docx^{(37.9KB, docx)}

Data Availability Statement

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

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PERMALINK

Efficacy and Safety of Yiqi Traditional Chinese Medicine Injections for Chronic Pulmonary Heart Disease: A Systematic Review With Pairwise Meta‐Analyses and Indirect Comparisons

Hongyi Yue

Jinxuan Chai

Hehe Liao

Yunfei Jia

Pingyi Wang

ABSTRACT

1. Introduction

2. Methods

2.1. Search Strategy

Figure 1.

2.2. Inclusion and Exclusion Criteria

2.3. Data Extraction

2.4. Risk Assessment and Quality Evaluation

2.5. Statistical Analysis

3. Results

3.1. Selection of Included Studies

Figure 2.

3.2. Characteristics of the Included Studies

Table 1.

3.3. Quality Assessment of Included Studies

Figure 3.

3.4. Quality Evaluation of Outcome Indicators

3.5. Clinical Efficacy

Figure 4.

Table 2.

3.6. LVEF

Figure 5.

3.7. PaCO2 and PaO2

Figure 6.

Figure 7.

Table 3.

3.8. The SUCRA Rankings Without Shenqi Fuzheng Injection

Figure 8.

3.9. Detection of Publication Bias

Figure 9.

3.10. Heterogeneity Tests

3.11. Meta‐Regression Analysis

3.12. Overall Model Fit and Leave‐One‐Out Robustness

Figure 10.

3.13. Adverse Reactions

4. Discussion

4.1. Strengths and Limitations

5. Conclusion

Author Contributions

Disclosure

Ethics Statement

Conflicts of Interest

Supporting information

Acknowledgments

Data Availability Statement

References

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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3.7. PaCO₂ and PaO₂