Deep venous thrombosis (DVT) is a common critical disease with very high incidence in elderly inpatients. Studies have shown that almost 20% of patients scheduled for orthopedic surgery have DVT, despite the use of preventative strategies [
This study systematically evaluated the efficacy and safety of Xueshuantong injection in treating DVT, in order to provide an evidence-based medical basis for the treatment of DVT.
The protocol for this systematic review has been developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [
It has been also registered on the INPLASY database (registration number: INPLASY2020120117).
The Chinese databases include Chinese National Knowledge Infrastructure Database (CNKI); the Chongqing VIP Database; Chinese Biomedical medical Database (CBM); and Wanfang Database.
The English databases include PubMed, Cochrane Library, Web of Science, Embase, and MEDLINE.
The search terms are “Panax notoginseng saponins”; “Panaxnotoginseng extract”; “Xueshuantong”; “XUESAITONG injection”; “Deep Venous Thrombosis”; “DVT”; “efficacy”; and “safety”.
The search time is from the establishment time of each database to November 1, 2020.
The complete search strategy for PubMed is reported in Table
Search strategy for PubMed.
Search strategy (PubMed database) | |
---|---|
Number | Search terms |
#1 | Xue Shuan Tong (MeSH) |
#2 | xueshuantong |
#3 | Xueshuantong injection |
#4 | Panax notoginseng extract |
#5 | Panax notoginseng |
#6 | #1 OR #2 OR #3 OR #4 OR #5 |
#7 | Deep venous thrombosis (MeSH) |
#8 | DVT |
#9 | venous thrombosis |
#10 | Deep venous thrombosis |
#11 | thrombosis |
#12 | #7 OR #8 OR #9 OR #10 OR #11 |
#13 | Randomized controlled trial (MeSH) |
#14 | Randomized controlled trial |
#15 | Controlled clinical trial |
#16 | Clinical trial |
#17 | trial |
#18 | #13 OR #14 OR #15 OR #16 OR #17 |
#19 | #6 and #12 and #18 |
Add search is the search by mainstream search engines (Baidu, Google); Clinical Research Registry (WHO International Clinical trial Registration platform; China Clinical trial Registration Center).
At the same time, the two researchers searched the literature independently, cross-checked the results, and further searched the references according to the search results.
The type is randomized controlled trials (RCTs).
The original study clearly pointed out that the included patients were in line with the relevant diagnosis of DVT. Refer to the guidelines for diagnosis and treatment of deep vein thrombosis [
The experimental group received Xueshuantong injection or Xueshuantong combined with conventional treatment (anticoagulation, thrombolysis, pressure treatment, and other clinical guidelines recommended treatments).
Incidence rate of adverse events:
Patency rate of femoral vein Patency rate of popliteal vein Patency rate of posterior tibial vein Circumference difference Activated partial thromboplastin time (APTT) The D-dimer (D-D)
The exclusion criteria were as follows: nonoriginal research; the outcome indicators not matching; key research data not fully displayed and not being able to be obtained; research reports repeatedly published; and data errors.
The two researchers independently screened the included literature and extracted the data. The differences encountered in the process can be resolved through negotiation, or they can consult experts in the research team to record the process.
In the case of missing data, we contacted the original trial investigators to request missing data whenever possible.
The quality evaluation tool is Bias Risk Assessment Tool developed by Cochrane Collaboration Network.
Evaluation items are as follows: how random sequences are generated; whether distribution is hidden; whether researchers and subjects are blinded; whether study outcomes are blinded; whether outcome data remain intact; selective reporting; and whether there are other biases.
RevMan 5.4.1 was used for data analysis and odds ratio (OR) or relative risk (RR) was used for the dichotomous variable and mean difference (MD) or standardized mean difference (SMD) was used for continuous variables and 95% CI was used to test the effect.
The heterogeneity was analyzed by using the
Trial Sequential Analysis (TSA) 0.9.5.10 (
A total of 330 potentially corresponding studies were identified by our primary search. After removing duplicate records, we identified 25 studies from 330 studies for review of the full text. A total of 13 studies were exempted for the following reasons: 5 articles are not RCTs, 4 articles are inappropriate types of intervention, 4 articles are repetitive publication, 1 article has not full text and 1 article is not peer-review paper. Of the 12 included studies, 1018 patients were used in this meta-analysis, as is shown in Figure
Flow chart of the search strategy.
The basic characteristics of the 12 RCTs are summarized in Table
Characteristics of the included studies.
Included study | Sample size (T/C) | Treatment | Gender (M/F) | Age (years) | Treatment course (days) | Random method | Evaluation indicators | |||
---|---|---|---|---|---|---|---|---|---|---|
Experimental group | Control group | Experimental group | Control group | Experimental group | Control group | |||||
Yang Xi, 2020 [ | 20/29 | Xueshuantong injection + low molecular weight heparin | Low molecular weight heparin | 0/20 | 0/29 | 56.45 ± 19.74 | 57.05 ± 21.74 | 14 | Random number table | 7;8;9 |
Lan Jinyao, 2019 [ | 91/91 | Xueshuantong injection + low molecular weight heparin | Low molecular weight heparin | 50/41 | 42/49 | 51.72 ± 16.82 | 48.73 ± 18.27 | 14 | Random number table | 1;7;9 |
Pei Guanghua, 2019 [ | 36/36 | Xueshuantong injection + urokinase injection | Urokinase injection | 20/16 | 21/15 | 62.9 ± 1.1 | 62.8 ± 1.2 | 14 | Random number table | 1;2;3;4 |
Shi Yiwen, 2019 [ | 38/38 | Xueshuantong injection + rivaroxaban | Rivaroxaban | 45/31 | 57.7 ± 4.5 | 14 | Drawing lots | 1;5;6 | ||
Wang Xiaobo, 2019 [ | 42/42 | Xueshuantong injection + urokinase injection | Urokinase injection | 27/15 | 25/17 | 68.7 ± 5.5 | 68.3 ± 5.6 | 14 | — | 2;3;4 |
Xu Chunyu, 2019 [ | 45/45 | Xueshuantong injection + urokinase injection + low molecular weight heparin | Urokinase injection + low molecular weight heparin | 25/20 | 24/21 | 59.12 ± 6.34 | 58.49 ± 6.28 | 14 | Random number table | 5;6;8 |
Chen Kui, 2018 [ | 34/34 | Xueshuantong injection + urokinase injection + low molecular weight heparin | Urokinase injection + low molecular weight heparin | 19/15 | 18/16 | 53.96 ± 18.95 | 54.14 ± 19.02 | 14 | Admission sequence | 1; 5;6;7;8 |
Pan Lei, 2018 [ | 63/63 | Xueshuantong injection + rivaroxaban | Rivaroxaban | 32/31 | 33/30 | 65.09 ± 4.12 | 65.24 ± 4.27 | 14 | Random number table | 1;7;9 |
Zhang Yanwen, 2018 [ | 25/25 | Xueshuantong injection + low molecular weight heparin | Low molecular weight heparin | 14/11 | 15/10 | 67.83 ± 7.24 | 67.19 ± 6.25 | 14 | — | 1;7;8;9 |
Zhou Bo, 2015 [ | 44/43 | Xueshuantong injection + low molecular weight heparin + warfarin | Low molecular weight heparin + warfarin | 30/14 | 29/14 | 64.3 ± 5.2 | 64.8 ± 5.5 | 10 | — | 1;8 |
Zhou Yuhu, 2015 [ | 39/39 | Xueshuantong injection + rivaroxaban | Rivaroxaban | 21/18 | 20/19 | 66.52 ± 3.63 | 66.61 ± 3.72 | 14 | — | 1;5;6;7;8;9 |
Zhang Jianping, 2012 [ | 28/28 | Xueshuantong injection + urokinase injection + low molecular weight heparin + aspirin | Urokinase injection + low molecular weight heparin + aspirin | 18/10 | 15/13 | 57.25 ± 13.64 | 55.31 ± 14.26 | 14 | Random number table | 2;3;4;9 |
Of the 12 studies, 8 [
Risk of bias graph with overall percentages of bias for each domain.
Risk of bias summary across all included studies.
Eight studies [
Forest plot of clinical effective rate for Xueshuantong injection in treating DVT.
Six studies [
Forest plot of the incidence rate of adverse events for Xueshuantong injection in treating DVT.
Three studies [
Forest plot of patency rate of femoral vein for Xueshuantong injection in treating DVT.
Three studies [
Forest plot of patency rate of popliteal vein for Xueshuantong injection in treating DVT.
Three studies [
Forest plot of patency rate of posterior tibial vein for Xueshuantong injection in treating DVT.
Four studies [
Forest plot of patency rate of circumference difference of upper knee limb for Xueshuantong injection in treating DVT.
Four studies [
Forest plot of patency rate of circumference difference of lower knee limb for Xueshuantong injection in treating DVT.
Six studies [
Forest plot of APTT for Xueshuantong injection in treating DVT (6 studies).
After excluding the two studies [
Forest plot of APTT for Xueshuantong injection in treating DVT (4 studies).
Six studies [
Forest plot of D-D for Xueshuantong injection in treating DVT.
A maximum of 8 outcome indices were available so no assessment of publication bias (e.g., funnel plot) could be made and the possibility of this form of bias cannot be excluded.
Sensitivity analysis was carried out by changing the statistical model and removing the recombination effect of a large sample study. This process did not change the results, indicating that the results of this study were robust.
The type I and type II errors were set at 0.05 and 0.2, respectively. The sample size was calculated with statistical power at 80%. The clinical effectiveness of Xueshuantong injection in the treatment of DVT was analyzed by experimental sequence analysis. The value (curve) crossed the traditional boundary value after the second study and crossed the TSA boundary value after the fourth study, indicating that the positive conclusion had been obtained before the amount of sample information in the current cumulative study had not reached the expected amount of information; that is, Xueshuantong injection is more effective than conventional treatment in the treatment of DVT, and that no further studies were needed for verification, as shown in Figure
Trial Sequential Analysis of clinical efficiency for Xueshuantong injection in treating DVT.
Deep venous thrombosis refers to abnormal blood flow and coagulation in the deep venous system [
The results of this study show that Xueshuantong injection can treat deep venous thrombosis effectively, with fewer adverse reactions and significantly better outcomes (including deep vein patency, circumference of lower extremities, D-dimer, and APTT) than conventional treatment. The results of the sequential analysis showed that the results of this meta-analysis are robust and may therefore have implications for evidence-based clinical practice. However, in view of the small sample size included and the low quality of literature methodology, the strength of this finding is limited, and more high-quality studies are needed to improve the level of evidence in the future.
Limitations of this study: this study compares Xueshuantong injection with conventional treatment, the latter encompassing anticoagulation, thrombolysis, and physiotherapy, which may have introduced heterogeneity. In addition, the included studies were all sourced from Chinese research databases. No relevant research was found in English language databases, and the representation of only one sector of the global population may have introduced bias. In the process of literature screening in this study, several articles were excluded because key data could not be obtained by the author, which may have biased the results. In addition, the quality of the research included in this study was low, with small sample sizes in some cases, which further reduces the certainty of conclusions.
Future prospects: future clinical research should use homogeneous outcome indicators to gradually establish a core outcome index set with indicators related directly to patient benefits. Higher quality research is needed with high integrity, standardized reporting, and reduced bias.
Based on the current analysis, compared with control, Xueshuantong injection as an add-on treatment provided better clinical efficiency for DVT with adequate power, while with fewer adverse reactions and significantly better outcomes (including patency of deep vein, circumference of lower extremities, D-D, and APTT), but this benefit should be considered with caution because of the small number of studies included in the meta-analysis and the high risk of bias of the included trials, suggesting that further studies are needed.
Randomized clinical trials
China national knowledge infrastructure
Chinese scientific journal database
Confidence interval
Mean difference
Relative risk
Deep venous thrombosis
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Standardized mean difference
Activated partial thromboplastin time
The D-dimer
Odds ratio
Trial Sequential Analysis
Required information size
The data used to support the findings of this study are included within the article.
The funders had not been involved in the design, execution, or writing the study.
The authors declare no conflicts of interest.
Wenhui Li, Changgeng Fu and Feng Xu contributed equally to this work and are co-first authors. WJF and CGF conceived the article, drafted the research protocol, retrieved the literature, analyzed the data, and wrote this manuscript. WHL and FX screened studies and evaluated the risk of bias. LX and XHW extracted data and gave suggestions for the discussion. RYH gave suggestions on the structure of the article. FX provided methodological guidance and gave suggestions on the conception of the article. All authors have read and approved this manuscript.
The authors thank Catherine Suttle, Ph.D., from Liwen Bianji, Edanz Group China (