Danshen (Chinese medicinal herb) preparations for acute myocardial infarction

doi:10.1002/14651858.CD004465.pub2

Intervention Review

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Danshen (Chinese medicinal herb) preparations for acute myocardial infarction

Taixiang Wu^1,*,
Juan Ni²,
Jiafu Wei²

Editorial Group: Cochrane Heart Group

Published Online: 21 JAN 2009

Assessed as up-to-date: 13 FEB 2008

DOI: 10.1002/14651858.CD004465.pub2

Database Title

The Cochrane Library

Additional Information

How to Cite

Wu T, Ni J, Wei J. Danshen (Chinese medicinal herb) preparations for acute myocardial infarction. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD004465. DOI: 10.1002/14651858.CD004465.pub2.

Author Information

¹
West China Hospital, Sichuan University, Chinese Cochrane Centre, Chinese EBM Centre, Chengdu, Sichuan, China
²
West China Hospital of Sichuan University, Clinical Epidemiology, Chengdu, Sichuan, China

^*Taixiang Wu, Chinese Cochrane Centre, Chinese EBM Centre, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, China. txwutx@hotmail.com. txwutx@public.cd.sc.cn.

Publication History

Publication Status: Edited (no change to conclusions)
Published Online: 21 JAN 2009

ARTICLE TOOLS

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Characteristics of included studies [ordered by study ID]

Chen 1984a

Methods	"Random allocation" was mentioned, but the method of randomisation unclear. In CYG 1981, the randomisation was described as "patients with odds numbers were allocated to TCM with western medicine group". Hence, we considered it a quasi-RCT. No blinding, baseline similar (P>0.05)

Participants	430 participants diagnosed by WHO 1979 criteria of AMI. Treatment group: 215 patients, M/F=150/65, age: 3 patients < 40 years; 45 patients = 41-50 years; 78 patients = 51-60 years; 57 patients = 61-70 years; 32 patients > 70 years. Control group: 215 patients, M/F=133/82, age: 9 patients < 40 years; 54 patients = 41-50 years; 61 patients = 51-60 years; 49 patients = 61-70 years; 42 patients >70 years. TCM signs were used to sort the type of patients. Of these patients, 232 were 'qixu xueyu zheng', some were 'yingxu xueyu' and 'xueyu', but the numbers were not mentioned.

Interventions	'Yiqi huoxue heji" decoction was taken orally, and water extraction of huangqi, danshen and huangjin named as 'yiqi' injection, water extraction of danshen, cishao and yujin called 'huoxue' injection were intravenous drip in the integrated TCM group. Both integrated TCM (group A) and western medicine (group B) groups were given routine treatment: monitor, isosorbide dinitrate 0.1g, dipyridamole 0.1g 3 times per day. No longer than six hours after enrolment, the patients in integrated TCM group were given both 'yiqi' injection and 'huoxue' injection by intravenous drip, and oral 'yiqi huoxue heji' decoction for 8 weeks.

Outcomes	Mortality: 14 deaths in the integrated TCM and western medicine group during the trial, while 32 patients died in the control group.

Notes	This was the second version of CYG 1981. This was the first ever study of danshen in the treatment of AMI. We decided to include this trial because of its position on the danshen therapeutic research for AMI although its randomisation may not be exactly correct that can be judged from its baseline not similar, for example, 10 patients complicated with the cardiogenic shock in the A group and 16 in the B group at the begining of treatment; 87 patients in the A group and 63 in control group complicated with heart failure; etc. In the other versions of this study, for example, Chen 1987 and Chen 1988, the method of randomisation was described as that "the odd number patients" were allocated to integrade TCM and western group, and the even numbers were allocated to the western medicine group. The number of patients in two groups were exactly equel: 215/215. So, this study was not considered as a RCT but a quasi-RCT, and there was a high potential risk of selection bias.

Chen 1984b

Methods	It was described that the participants with AMI where allocated into two arms by critical randomisation. But the method was not mentioned. No blinding.

Participants	224 AMI patients diagnosed by WHO criteria and no longer than 72 hours after onset were included and equally allocated to two groups. Of these patients, M/F 159/65; 121 patients older than 60 years old; 168 patients with infarction at anterior or/and antesepterior or/and inferior myocardial infarction; 119 patients complicated with hypertension, some with cerebral disease or/and diabetes. There was no any significant difference between two groups on baseline.

Interventions	'Yiqi huoxue' injection was the water abstration of huangqi, danshen, huanjin, chishao, yujin. Routine treatment (western medicine) was given in both two groups, and the 'yiqi huoxue' injection was used by intravenous drip in a does of 10 mL in 250 mL 5% glucose infusion within 6 hours after enrolment.

Outcomes	1. Mortality: 8 participants died in integrated TCM and western group and 14 in control group; The causes of death also been reported; 2. The number of complications including hypotension, shock happend during treatment in integrated TCM and western medicine group was statistically significant fewer than that in the control group; but no data can be used; 3. the number of heart failure in integrated treatment group during the treatment was significantly fewer than in control group, but no data can be used.

Notes	1. This was a abstract only, no whole text of the paper can be found; 2. We did not interview the original author, the evaluating was made depends on the report; 3. The authors considered that 'yiqi huoxue zhusheye' can reduces the death rate in the first week of treatment, improved partial patients' prognosis, and may preventing AMI complications including hypotension, shock, heart failure. 4. The western medicine "routine treatment" not been specified in detail.

Chen 2001

Methods	"Patients were randomly allocated to two groups" was mentioned, but lack of description about the method. The original authors unable to provide the information of randomisation in detail. Parallel design. No blinding.

Participants	All participants were enrolled within 2 days of the AMI onset. 61 in 'quyu huatan xiezhuo' group, M/F 46/15, 38 to 89 years, average 63.7. Of these patients, 9 were 'qixu xueyu zheng', 3 with 'both qi and yin xu zheng', 4 with 'tanshi zhuci zheng' and 45 with 'tanyu huzhu zheng'. 60 in 'yiqi huoxue' group, M/F 43/17, 34 to 90 years old, average 63.8. Of those patients, 6 with 'qixu xueyu zheng', 3 with 'both qi and yin xu zheng', 3 with 'tanshi zhucu zheng' and 48 with 'tanyu huzhu zheng'. Severity of AMI at baseline was similar between groups.

Interventions	The basal treatment was same in two groups. All participants were treated by nitroglycerin and polarisation liquid by intravenous drip, and oral isosorbide dinitrate, captopril, aspirin enteric coated tablets, etc. Expectant treatment was used for those who with complications. In the experimental group, used 'quyu huatan xiezhuo fang'. In the control group, used 'yiqi huoxue fang'.

Outcomes	1. frequency of angina pectoris; 2. change of lung moist rales; 3. change of arrhythmia.

Notes	1. Wu TX telephed Professors Chen KY and Shi DZ in 23 Auguest, 2007. They don't remember the method of the randomisation and other information in detail due to the trial was conducted ten years ago. Prof. Chen said the allocation sequence seem was generated by statistician, "a random number table seem was took out from computer." 2. The paper was published in 2001, but the study was conducted during Jan. 1996 to Dec. 1998; 3. The number of death was reported in the 'Result' section although it did not be included in the 'outcomes' of 'Methods' section; 4. There is no any useful data for analysis, the description about the results were extremely simple.

Li 2004

Methods	"Randomly allocated patients into three groups" was mentioned, but no any description about the method of generation the sequence. TW tried to contact the authors for further information, but they could not be located. Parallel groups. No blinding.

Participants	Total 175 AMI patients were included from 1997 to 2002. 41 participants in group 1, 58 in group 2 and 76 in group 3. Similar in baseline includes age, sex, position of AMI, type of TCM 'zheng'.

Interventions	Same basal treatment for three groups. Group 1 used huangqi injection 20 mL and fufang danshen injection 20 mL intravenous drip twice daily for 2 weeks; Group 2 used shenmai injection 20mL and fufang danshen injection 20mL intravenouse drip twice daily for 2 weeks; Group 3 use basal treatment only (oxgen supply, antipaint, anticoagulation, etc, no description about the drugs in details.

Outcomes	1. Mortality. 2. Rate of severe arrhythmia. 3. Rate of heart failure.

Notes	1. Although this study is included in the review, but there are some doubtful points for its reliability of randomisation, for example, the arms were not balanced (41:58:76), no any explanation for this odd rate. 2. 76 patients were included in the control group, but in the Results section, the number was became '68 patients', no any explain for this change.

Wang 1994

Methods	"Random allocation" was mentioned but the method was not clear. Blinding not used.

Participants	Danshen group included 388 participants, M/F=295/93, average age was 66+/-9 years; control group included 962 patients, M/F=712/250. Average age was 67+/-10 years.

Interventions	Danshan group: danshen injection 16˜24 g with 500 mL 5% glucose injection or low molecular dextran by intravenous drip, one time a day, 7˜14 days a course.

Outcomes	Mortality: Danshen group: M 48/295, F 34/93; Control group: M 158/712, F 89/250

Notes	1. The description about the randomisation in the original text was not clear: "all of the patients were randomly allocated to danshen group and control group depends on whether they used danshen injection or not". Following a telephone interview with the original author the method was judged inadequate; it's clear that the patients were given danshen injection optionally by the doctors, and the allocation to intervention or control groups followed treatment; 2. Although it was judged as a retrospective study, we still included it as it is an important study in the history of danshen for AMI, and the member hospitals of this study are high level hospitals in Shanghai, included Huashan Hospital and Zhongshan Hospital of Fudan University, Shanghai Cardiavascular Diseases Institute, Shanghai Second University of Medical Sciences Affiliated Ruijin Hospital and Renji Hospital, Xinhua Hospital. There should be some value for reference.

Zhang 1996

Methods	"Randomly allocated patients to two groups" was mentioned, but lack of description about the method of randomisation. Parallel groups. No blinding.

Participants	Participants with AMI were enrolled after 30 minutes to 6 hourses of AMI onset during 1991 to early 1995. 34 participants in isosorbide dinitrate group, M/F 25/9, 33 to 82 years old (average 64.2+/-8.55), heart function I grade 29 and II grade 5 cases. 34 participants in control group, M/F 28/6, 40 to 82 years old (average 64.8+10.21), heart function I grade 30 and II grade 4 cases.

Interventions	All participants were kept given strict bed rest. Isosorbide dinitrate was given in both groups. Isosorbide dinitrate group: 20 mg isosorbide dinitrate via intravenous drip 4˜7 hours a day for 2 weeks; after 2 weeks, oral 10 mg, three times a day. Control group: oral isosorbide dinitrate 10 mg, three times a day, fufang danshen 16 mL a day via intravenous drip for 2 weeks.

Outcomes	1. Heart function, used Killin grade.

Notes	1. TW tried to contact the original author but did not receive any further information. The impression from this paper is that it is a case records analysis not a trial due to its long duration and poor description. It is included because there is no evidence to demonstrate it is not an RCT since the original authors cannot be found; 2. The original study did not use mortality as the primary outcome, but in the Results, number of death was reported; 3. There was no description about the measure of heart function in detail, the result was reported as percentage only.

TCM - traditional Chinese medicine
'zheng' - a TCM sign

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion

Cha 1998	The aim of this article was to assess the effect of bothropsatrox antithrombusase but not danshen, the latter was used as control. The result was that the bothropsatrox antithrombusase much better than danshen on marked improvement and reducing death. The "randomly allocated the patients" was mentioned, but it was judged as optional allocation. Dr. Cha said that her assistant developed a protocol. For the reason of unbalanced arms (14 versus 8), she explained that most patients were loss of follow-up. So, the study was judged as a non-RCT for the reason of 1. only Dr Cha was the sole author, 2. the AMI patients unable to loss of follow-up in a two weeks treatment duration. The author was interviewed in 18 June, 2007 by number 86-0755-26537163.

Chen 1987	The fourth version of CYG 1981.

Chen 1988	The fifth version of CYG 1981.

Chen 1996	"Randomly allocation" mentioned. But in the description about the method of randomisation, the method was described as "those not willing to accept TCM or hypersusceptibility to TCM were allocated to control group". Thus, this study was not considered as RCT.

Chen 2004	The aim of this article was to assess the effect of bothropsatrox antithrombusase but not danshen, the latter was used as control. And the patients included not only AMI (29 patients) but also included 163 patients with myocardial ischemia without AMI. The result was that the bothropsatrox antithrombusase was much better than danshen on marked improvement.

Cui 1983	The outcomes of interest were not reported.

Cui 2004	Randomly allocation was mentioned. But numbers of male and female in two groups were not balanced, in the danshen group, the number of male was 36/46, and in the control group it was 28/46, respectively. It thus be considered as an optional allocation study.

CYG 1981	This was the first clinical study about danshen formulation preparation for AMI. We do not include this article due to it was included in Chen 1984, and the use of intervention did not be described clearly.

Deng 1998	This study aims to assess combined shenmai injection with danshen injection in the treatment of AMI, so, the shenmai was a confounder factor for assessing danshen. Wu TX telephoned Dr. Deng, the first author, in 24 Aug. 2007, he said this paper was wrote when he was a residency ten years ago, and was a retrospective case records analysis.

Dong 2002	Not an RCT

GAM 1984	The third version of CYG 1981.

Han 1992	Not an RCT.

He 2000	The aim of this article was to assess the effect of bothropsatrox antithrombusase but not danshen, the latter was used as control. The result of reducing mortality was the bothropsatrox antithrombusase much better than danshen. The "randomly allocated patients" was mentioned. But it actually was a retrospective study. This was know by telephoning the third author of the paper. Dr. Li Yinjun answered my question and said "we did not develop a protocol previously, we allocated the patients not strictly, just by physician's selection and "time window" of disease. The author was interviewed in 18 June, 2007.

Li 1995	The aim of this article was to assess the effect of bothropsatrox antithrombusase but not danshen, the latter was used as control. The result was that the bothropsatrox antithrombusase was much better than danshen on death from AMI. "Randomly allocated the patients" mentioned, but it was actually a retrospective study. This was known by telephoning the Dr. Li, the original author. He was interviewed in 20 June, 2007.

Li 2003	Not an RCT

Liang 1999	Outcome measures of interest not reported

Liang 2000	This study aims to compare the effect of combined use of urokinase with shenmai injection and danshen injection versus urokinase alone. The interesting thing was that the former was much better than the latter on vessel recanalisation rate, reducing mortality, bleedding complication, and shock, heart failure. Wu TX telephoned Prof. Liang, the first author, in 24 Aug. 2007. Prof. Liang has promoted to as the director of Guangxi TCM Collage office. He said that this was a retrospective paper of case records analysis, no protocol was developed previously.

Liang 2001	"Randomly allocation" was mentioned, but the original auhtor was interviewed by telephone and it was understood that the patients were actually allocated by optional selection.

Liu 1998	"Large sample size, randomised, double blind controlled trial" was mentioned. But the "randomisation" was described as "randomly took drugs", of the 14,962 patients with AMI, 34.8% patients randomly used danshen injection. So, this study was considered a non-randomised controlled study.

Liu 2006b	"Randomly allocation" was mentioned. But it was discovered telephone interview that this was not a real RCT. The patients were allocated based on patients' opinion but not by any random method.

Luo 2001	The randomisation was described as "the patients were randomly allocated by the order of admission". So, it was considered as an optional allocating study.

Qian 1996	This study aims to assess the effect of integrated TCM therapy includes aupuncture and danshen multiple compound decoction and western medicine versus western medicine alone. So, the effect of danshen compound cannot be assessed separately. Wu TX telephoned the second author, Dr. Tian ZZ on 23 Aug. 2007. Dr. Tian said that this was an analysis for case records data and no protocol was developed before study.

Shi 2000	Outcome measures of interest not reported

Sun 1992	The randomisation was described as that the patients were allocated by the order of admission. So, the method was considered as optional allocation.

Sun 1997	The randomisation was descibed as that the patients were allocated by the order of admission. So, it was considered as an optional allocating study rather than RCT.

Tang 1999	This study aims to compare the effect of shenmai injection to danshen injection. The result was that the former is much better than the latter on the reducing mortality and improving heart function, the general improvement rate also showed that the former much higher than the latter. Wu TX telephoned Dr. Tang, the original author, in 27 Aug. 2007. Dr. Tang did not develop a protocol previously for this study, because this was a data analysis for case records only.

Wang 1995	The randomisation was described as that the patients were allocated according to the order of admission. So, it was considered as an optional allocation study ranther than RCT.

Wang 1999	The aim of this article was to assess the effect of bothropsatrox antithrombusase but not danshen, the latter was used as control. The result was that the bothropsatrox antithrombusase was much better than danshen on mortality (rate of death from AMI). "Randomly allocated the patients" mentioned. But some of the patients used danshen injection, others used mailuoning injection in control group. It can be judged very clearly that the study did not well designed. It cannot be included because we cannot devide who was treated by danshen and who was by mailuoning, even if it is an authentic RCT. Taixiang Wu had tried to contact the author, but none of the authors can be found.

Wang 2000	The randomisation was described as that the patients were allocated by the order of admission. Thus, we considered it an optional allocation study rather than a RCT.

Wang 2003	Outcome measures of interest not reported

Wu 2005	The outcomes did not match inclusion criteria of this review.

Xie 2001	The aim of this study was assess for effect of dan ao, the fufang danshen injection was used as control. The effect of dan ao was better than the control. Wu TX telephoned Dr. Xie, the first author of the paper, in 23 Aug. 2007. Dr. Xie said that this was a retrospective study by collecting cases reports during last year.

Xu 2001	This study aims to demonstrate the self-prepared formulation "Wutou ChiShizhi Tang" decoction combined with Danshen injection. So, the decoction was a confunding factor. Wu TX telephoned Dr. Xu GH in 27 Aug. 2007. Dr. Xu said this was a case records analysis for inpatients, no protocol was developed previously.

Xu 2003	Not an RCT

Yang 1997	The randomisation was described as that the patients were allocated according to order of admission. So, the method was considered as optional allocation.

Ye 2006	The aim of this article was to assess the effect of bothropsatrox antithrombusase but not danshen, the latter was used as control. The result was that the bothropsatrox antithrombusase was much better than danshen on marked improvement and reducing death from AMI. "Randomly allocated the patients" was mentioned. Taixiang Wu telephoned the original author, Director Ye, and understood that this was not a real RCT. The patients were allocated optionally by doctor, or depended on the price of drug, etc. The author sounds misunderstanding the concept of randomisation.

Yuan 2003	Not an RCT

Zhang 1999	The randomisation was described that the patients were allocated according to the order of admission. Thus, it was considered as an optional allocation study.

Zhang 2001	Outcome measures of interest not reported

Zhong 2000	The outcome measures not match the including criteria.

Zhou 1996	The randomisation was described as that the patients were allocated according to the order of admission. Thus, it was considered as an optional allocation study.

Zhou 1998	This study aims to assess the effect of integrated TCM and western medicine versus western medicine alone. TCM included danshen injection, huangqi injection and shexiang baoxin wan tablet. Wu TX telephoned Dr. Zhou. She said that this was a cases records analysis, no protocol was developed before the study. Date of interview is 23 Aug. 2007.

Zhu 2000	Randomisation allocation was mentioned in the text, but it can be judged as a non-RCT because the patients were allocated to the treatment group based on those who suit for thrombolytic thereapy, and if not, they were allocated to the control group.

Comparison 1. Danshen compunds + western medicine versus western medicine

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality