Meta-analysis of the efficacy and safety of ginkgo diterpene lactone meglumine injection combined with western medicine in the treatment of cerebral infarction (26 studies, 2332 patients)

【Foreword】

【Foreword】

Cerebral infarction is a common clinical acute cerebral vascular disease, refers to avascular necrosis or softening due to brain blood circulation disorders, ischemia, hypoxia-induced focal brain tissue, and thus a corresponding neurological deficit
.

Brain stroke, now has become a cause of death and disability One of the most important diseases, there are five people in our country about the new hair stroke per minute, which accounts for about 70% of all cerebral stroke patients, and its incidence populations exhibit Obvious trend of younger generation

Vascular stroke prevention

【Research methods】

【Research methods】

1.
Literature sources

Computer search of China Knowledge Network (CNKI), VIP database (VIP), WanFang database (WanFang), Chinese Biomedical Literature Database (CBM), Pubmend, Cochrane Library, and manual search of various paper-based journals and conference proceedings, Collect all the literature on randomized controlled trials of DGMI combined with western medicine in the treatment of cerebral infarction
.

Chinese search keywords: "ginkgo diterpene lactone meglumine injection", "cerebral infarction", "ischemic stroke", "cerebral infarction", etc.

2.
Inclusion and exclusion criteria

Inclusion criteria ①Research type: Clinical randomized controlled trial (RCT), with clear reports on related efficacy indicators or adverse drug reactions
.

②Research objects: Patients who meet the diagnostic criteria of cerebral infarction in the "Key Points for the Diagnosis of Major Cerebrovascular Diseases in China 2019" and have been clearly diagnosed by CT or MRI

diagnosis

Exclusion criteria ①Non-clinical randomized controlled trials such as literature review, case or experience summary, basic research; ②The trial data in the literature is missing, and complete data cannot be obtained by contacting the original author; ③The observation group only uses DGMI, or the control group uses The literature of other proprietary Chinese medicines; ④Remaining one of the repeated publications
.

3.
Method

The literature quality evaluation conducted methodological quality and bias analysis and evaluation of the included literature based on the Cochrane bias risk evaluation criteria, including: the generation of random sequences, the implementation of allocation concealment and blinding, the completeness of the outcome index data, the selective outcome report, and Other biases that may exist
.

If there is a discrepancy between the opinions of the included literature, the relevant experts shall be consulted for decision

Data extraction by two or more related professional researchers independently extracted data included in the study, include: first author and year of publication, the observation group and the control group sample size, intervention, drug treatment, outcome indicators
.

4.
Statistical processing

Collect and organize data through EXCRL tables, and then use RevMan 5.
3 software for analysis
.

Use the I2 test to analyze the heterogeneity of the included studies.

【Research result】

【Research result】

1.
Included literature

1.
Included literature

A total of 275 related documents were obtained through preliminary search.
After the NoteExpress 3.
2.
0 software and manual screening, 26 documents were finally included
.

The screening process is shown in Figure 1

2.
Methodological quality evaluation of included literature

2.
Methodological quality evaluation of included literature

Among the 26 documents, 25 documents describe the random method grouping, and only 13 documents [6-7,10,12-13,16-19,24,29-31] specify the random method, of which 7 documents [6,10,16,18,24,29,31] Using random number table method, 2 documents [7,17,30] using lottery method, 1 document [19] using ball method, 2 documents[ 12-13] According to the order of admission; all the literature has complete outcome data; all the literature does not specify whether to implement allocation hiding; all the literature does not specify whether to blind the subjects, interveners, and outcome evaluators
.

Therefore, the overall quality of the literature is low

Figure 2: The risk of bias in the included studies

Figure 2: The risk of bias in the included studies Figure 2: The risk of bias in the included studies

3.
Meta analysis results

3.
Meta analysis results

3.
1 Overall clinical efficacy

A total of 20 studies [6-14, 18-21, 24-30] reported on the overall treatment effect, with homogeneity among the studies (I2 = 28%, P = 0.
12), and a fixed-effect model was used for Meta analysis
.

The results showed: RR=1.

3.
2 BI score

There are 12 studies [9, 12-13, 15, 18-19, 21-23, 25, 29-30] reported on the improvement of BI scores, and there is heterogeneity among the studies (I2=89%, P<0.
00001 ), using random effects model for Meta analysis
.
The results showed: MD = 10.
24, 95% CI (7.
53 ~ 12.
95), P <0.
05
.
It shows that the BI score after DGMI combined with western medicine treatment is higher than that of western medicine treatment alone, and the difference is statistically significant
.

3.
2 NIHSS score

A total of 24 studies [6-11, 13-18, 20-31] reported on the improvement of NIHSS scores, and there was heterogeneity among the studies (I2 = 97%, P <0.
00001), and the random effects model was used for Meta analysis
.
The results showed: MD = -3.
08, 95% CI (-3.
94 to -2.
22), P<0.
05
.
It shows that the NIHSS score after DGMI combined with western medicine treatment is lower than that of western medicine treatment alone, and the difference is statistically significant
.

4.
Security Analysis

A total of 18 studies have reported adverse drug reactions [6-7, 12, 14-16, 18-24, 27-31], including 9 studies [6, 12, 14, 16, 19, 21-23, 31] ] Adverse reactions occurred, among which the more common adverse reactions mainly include nausea, dizziness, skin rash, abdominal pain, abnormal liver function, and thrombocytopenia
.
The 9 studies with adverse reactions were combined and analyzed, and the studies were homogeneous (I2=24%, P=0.
23), and the fixed-effects model was used for meta-analysis
.
The results showed: RR=0.
76, 95% CI (0.
49～1.
19), P=0.
23
.
It shows that the addition of DGMI on the basis of conventional western medicine treatment will not significantly increase the adverse reactions of patients with cerebral infarction
.

5.
Sensitivity analysis

After removing individual studies one by one, the remaining original studies were re-analyzed by Meta analysis, and the results were not significantly different from the overall combined analysis.
Therefore, the results of this study can be considered as stable
.

【discuss】

【discuss】

Cerebral infarction is also called ischemic stroke.
Chinese medicine believes that the occurrence of ischemic stroke is mainly related to the imbalance of yin and yang viscera, the disorder of qi and blood, the production of wind, fire, phlegm, and blood stasis, and the blocking of the brain collaterals
.
At present, Western medicine treatment mainly focuses on improving the blood circulation of the brain, nourishing the brain nerves, and protecting the brain tissue.
The treatments are mostly intravenous thrombolysis, intravascular interventional therapy, anticoagulation, anti-platelet aggregation, fibrillation, expansion, and expansion of blood vessels.

.
The pathogenesis of cerebral infarction is very complicated.
Although western medicine treatment can effectively improve the symptoms of neurological deficits, it is easily affected by factors such as time window, and even hemorrhage transformation occurs
.
Research by Li Jihong and others found that on the basis of sodium ozagrel treatment, the combined use of ginkgo biloba preparations can effectively improve the neurological deficit of patients with cerebral infarction and improve the therapeutic effect
.
Zhong Chongjin and other studies have found that DGMI can improve neuromotor function, increase the activity of superoxide dismutase (SOD), reduce the activity of creatine kinase (CK), lactate dehydrogenase (LDH), and malondialdehyde (MDA), Interleukin 1 β (IL-1 β) level reduces cerebral edema and reduces the volume of infarcted brain tissue
.
In addition, ginkgo terpenoids also have a variety of biological activities such as anti-oxidative stress, alleviating inflammation and reducing the permeability of the blood-brain barrier
.
DGMI is a new type of ginkgo biloba extract preparation, which has the effect of promoting blood circulation and dredging collaterals.
It is mainly used to treat various ischemic cardiovascular and cerebrovascular diseases
.
Modern pharmacological studies have shown that DGMI has the effects of removing excessive free radicals in patients with cerebral infarction, anti-platelet aggregation and improving blood circulation in the brain
.
Zhao Binjiang et al.
found through clinical trials that DGMI can combat the formation of thrombus in patients with cerebral infarction , relieve cerebral ischemia and hypoxia, reduce nerve cell apoptosis, and protect brain tissue
.

thrombus

This study conducted a systematic evaluation and meta-analysis of the overall effective rate, BI score, NIHSS score, and drug safety of clinical studies related to the treatment of cerebral infarction by DGMI combined with conventional western medicine
.
The results showed that the overall clinical efficacy of DGMI combined with conventional western medicine in the treatment of cerebral infarction is better than that of conventional western medicine alone [total effective rate: RR=1.
22, 95% CI (1.
17～1.
28), P<0.
05], and it can significantly improve the patient’s Activities of daily living [BI score: MD=10.
24, 95%CI (7.
53~12.
95), P<0.
05] and the degree of neurological impairment [NIHSS score: MD=-3.
08, 95%CI (-3.
94~-2.
22), P<0.
05], there is no significant difference between adverse reactions and conventional western medicine treatment [safety: RR=0.
76, 95%CI (0.
49～1.
19), P=0.
23]
.

It is worth noting that (1) the original studies included were small-sample trials with a single center; (2) some studies did not specify the specific random sequence generation method; (3) all the studies did not specify whether to implement allocation concealment and Blind method, (4) does not describe whether there are cases falling or withdrawing.
These factors will affect the reliability of the results of this Meta-analysis
.
Therefore, in the future, more reasonably designed, qualified multi-center, large sample, high-quality double-blind randomized controlled trials are still needed to further verify the efficacy and safety of DGMI combined with conventional western medicine treatment on cerebral infarction
.

【in conclusion】

【in conclusion】

In summary, based on the existing clinical evidence, the addition of DGMI to conventional western medicine treatment can effectively improve the clinical effect of cerebral infarction treatment, and can promote patient recovery, improve patient prognosis, and improve patient quality of life.
There is a need for further clinical trials.
Conduct in-depth discussions on clinical research with rigorous design and high scientificity (such as blinding)
.

Original source:

Original source:

Efficacy and safety of Western medicine treatment of cerebral infarction Meta-analysis ZHANG Ling Lin, even Fu, Zhao Jing and so on.
Ginkgo Lactone meglumine injection combined.
China nerve immune Journal and Neurology, 2021,28 (2).

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