|Year : 2019 | Volume
| Issue : 2 | Page : 39-42
Efficacy and safety of Le-Mai particle in patients with angina pectoris
Ming Shi1, Yaqian Shen1, Aifeng Zhang2, Zhongwen Zhang3, Panpan Hao4
1 Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Shandong University Qilu Hospital; Department of Medicine, Division of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China
2 Department of Nephrology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA
3 Department of Medicine, Division of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China
4 Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Shandong University Qilu Hospital, Shandong University, Jinan, Shandong, China
|Date of Submission||04-May-2019|
|Date of Acceptance||15-May-2019|
|Date of Web Publication||26-Jun-2019|
Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Shandong University Qilu Hospital, Jinan 250012, Shandong
Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014
Source of Support: None, Conflict of Interest: None
This study aimed to verify the efficacy and safety of the Le-Mai particle in patients with angina pectoris. Randomized controlled trials (RCTs) were searched from numerous databases. Clinical symptom improvement was served as the primary endpoint and electrocardiogram (ECG) improvement as the secondary endpoint to testify the efficacy of Le-Mai particle. The safety of Le-Mai particle was also evaluated. Six RCTs were included in our analyses. Two hundred and seventy-nine patients treated with Le-Mai particle in combination with conventional western medicine (CWM) and 278 patients treated with CWM alone were enrolled. Treatment with Le-Mai particle exhibited a better therapeutic effect on both angina symptom improvement (odds ratios [OR] = 3.85, 95% confidence intervals [CI] = 2.38–6.24,P < 0.00001) and ECG improvement (OR = 1.98, 95% CI = 1.38–2.85,P = 0.0002) as compared to the control group. When compared with CWM alone, no significant increase in the adverse reaction was observed in the Le-Mai group. The study provided preliminary evidence that complementary therapy with the Le-Mai particle is effective and safe in patients with angina pectoris.
Keywords: Angina pectoris, Le-Mai particle, pooled analysis
|How to cite this article:|
Shi M, Shen Y, Zhang A, Zhang Z, Hao P. Efficacy and safety of Le-Mai particle in patients with angina pectoris. Cardiol Plus 2019;4:39-42
| Introduction|| |
Coronary heart disease (CHD), also known as ischemic heart disease, refers to a group of diseases which include stable angina, unstable angina, myocardial infarction, and even sudden cardiac death., The World Heart Federation reported that CHD accounts for 17.3 million deaths/year and probably 23.6 million deaths by the year 2030. Angina pectoris is the most common type of CHD. Although the current therapies are effective in controlling symptoms and delaying the progression of CHD in some cases, there are still a large number of patients suffering from this disease.,,,,, Therefore, it is urgent to look for other treatments for CHD.
Le-Mai particle is composed by Salvia miltiorrhiza Bunge (31.9%), Ligusticum chuanxiong Hort (15.9%), Radix Paeoniae Rubra (15.9%), Carthamus tinctorius L.(15.9%), Cyperus rotundus (7.9%), Radix Aucklandiae (7.9%), and Crataegus pinnatifida Bunge (7.9%).,, Le-Mai particle has been used for many years to supplement Qi and activate blood circulation in China. In 2018, Le-Mai particle was approved in Canada to treat stable angina pectoris. Although extensive researches investigated the effectiveness and safety of Le-Mai particle in patients with angina pectoris,,,,,,, the conclusions obtained from different studies were not consistent with each other. What's more, the sample sizes of most researches were not enough to reach a convincing conclusion, and few pooled analyses have been carried out on CHD treatment with Le-Mai particle. Therefore, we systematically screened data for Le-Mai particle aiming to provide the evidence for the efficacy and safety of Le-Mai particle in patients with angina pectoris.
| Subjects and Methods|| |
In order to obtain as many randomized controlled trials (RCTs) of Le-Mai particle therapy in patients with angina pectoris as possible, we searched the following databases from inception through August 1, 2018: China National Knowledge Infrastructure database, Wanfang database, China Science and Technology Journals database (VIP), Chinese Biomedical Literature database, PubMed, Cochrane Library, and Medline. We also used Internet resources to gather information (http://www.clinicaltrials.gov.http://www.clinicaltrialresults.org). The following terms were used: “Le-Mai particle” or “Le-Mai” or “Le Mai” in combination with “Angina pectoris” or “Angor pectoris” or “Angina” or “Acute coronary syndrome” and “CHD” or “Coronary artery disease” or “Cardiovascular disease” or “Angiocardiopathy” or “Atherosclerosis.” There was no restriction on language or the type of publication.
The inclusion criteria for studies were as follows: (1) RCTs; (2) participants were diagnosed with angina pectoris according to the criteria determined by the International Society of Federation of Cardiology and the World Health Organization; (3) experimental groups were treated with Le-Mai particle, regardless of blinding; (4) the evaluation of clinical curative effect should have recognized observational indexes and exact values, such as angina pectoris improvement rate, electrocardiogram (ECG) improvement rate, and cardiac function grading; (5) the sample size ≥40 in each group. The exclusion criteria were as follows: (1) incompatible or repeated research; (2) unclear diagnosis of the selected population; (3) lack of control group or other Chinese medicine were used as the control group; (4) incorrect or incomplete data; (5) no objective laboratory examination but only the evaluation of traditional Chinese medicine (TCM) treatment; (6) animal or cell experiments.
Data extraction and quality assessment
Data concerning details of participants, interventions, and outcomes were extracted independently by two reviewers. For dichotomous data, the number of total events and positive events in each group was extracted. For continuous outcomes, mean value, standard deviation, and the sample size of each group were imputed. The data extraction table included the following items: (1) general information: title, authors, and year of publication; (2) trials characteristics: design of independent researches and methods of randomization; (3) patients: total number, the number of the experimental group and the control group, age, diagnostic criteria, and withdrawals/losses to follow-up; (4) interventions and outcomes. Main observation indexes in this research included clinical angina improvement as the primary endpoint and ECG improvement as the secondary endpoint. The methodological quality of the included studies was scored using a modified Jadad scale. Trials scoring 1–3 points were considered as low quality, whereas trials scoring 4–7 points were defined as high quality.
Data were analyzed using RevMan version 5.2 (Cochrane Collaboration, London, UK). Dichotomous data were analyzed using odds ratios (OR) with 95% confidence intervals (95% CI), and continuous variables were analyzed using standardized mean differences with 95% CI. The Chi-square test and I2 statistic were used to assess the heterogeneity between the results of trials. When P > 0.1 and I2 <50%, a fixed-effect model was applied. Otherwise, the random-effect model was applied. All P values were two-tailed, and the threshold for statistical significance was set at 0.05. The improvement rate of clinical symptoms was the primary evaluation index of drug efficacy. The clinical symptom improvement was defined as the frequency of angina pectoris reduced by >1/2 in 1 week, under the condition of patients maintaining the same labor intensity as before. ECG was one of the most crucial objective laboratory examinations. Hence, it was also used to evaluate the effect of Le-Mai particle on the treatment of CHD. ECG improvement was defined as ST segment increasing at least 0.05 mV or reaching nearly normal level under exercise test. If the number of included trials was adequate, funnel plot in combination with the fail-safe number (Nfs 0.05) was chosen to assess the potential publication bias.
| Results|| |
| Literature Searching Results|| |
After inputting search terms in all database and websites as mentioned above, 46 records were identified. Among the 46 articles, 34 with repetitive contents were deleted and 12 remaining records were downloaded for elaborative assessment. Four records were excluded due to not meeting the inclusion criteria. One record was excluded because it used other Chinese medicine in the control group. One record did not have objective laboratory examination. Finally, a total of six records were found to be well qualified.,,,,,
Basic characteristics and quality assessment of included studies
Six RCTs,,,,,, enrolling 557 patients with angina pectoris, were identified in the study. 279 patients in the experimental group were treated with Le-Mai particle and conventional Western medicine (CWM), and 278 patients in the control group were given CWM alone for treatment. The quality of the included studies was generally low. Jadad scores for all studies were no >3 points. The basic characteristics of the six included studies are shown in [Table 1].
As shown in [Table 2], treatment with Le-Mai particle exhibited a better therapeutic effectiveness in both angina symptom (OR = 3.85, 95% CI = 2.38–6.24, P < 0.00001) and ECG improvement (OR = 1.98, 95% CI = 1.38–2.85, P = 0.0002) in comparison with control therapy.
The adverse reaction was used to evaluate the safety of Le-Mai particle in patients with angina pectoris. All literature involved mentioned adverse reaction. When compared with CWM alone, no significant increase in the adverse reaction was observed in the Le-Mai treatment group. Further studies with larger sample sizes were needed to confirm the result.
Publication bias and sensitivity analysis
In this study, funnel plots and Nfs 0.05 were used to analyze the publication bias of the observed outcomes. The funnel plot was roughly symmetric, which meant that no conspicuous publication bias was found (data not shown). The Nfs 0.05 value of clinical angina effect was calculated as 58.3, which meant that 58.3 negative independent studies were required to reverse the conclusion. The Nfs 0.05 value of ECG improvement was counted as 23.5, which meant that 23.5 negative independent studies were needed to deny the efficacy of Le-Mai particle on ECG improvement. Both 58.3 and 23.5 were higher than 6 (six independent studies involved in our analysis). Thus, there was no significant publication bias in the pooled analysis.
| Discussion|| |
Our study showed that Le-Mai particle was effective in improving clinical angina symptoms and abnormal ECG. No significant increase in the adverse reaction was observed in the Le-Mai treatment group compared with the control group. To the best of our knowledge, this is the first pooled analysis providing comprehensive insights into the efficacy and safety of Le-Mai particle on angina pectoris. Our pooled analysis provided strong evidence that Le-Mai particle could be widely used in clinical for patients with angina pectoris.
Le-Mai particle, as one complicated prescription, is composed by S. miltiorrhiza Bunge (31.9%), L. chuanxiong Hort (15.9%), Radix Paeoniae Rubra (15.9%), C. tinctorius L (15.9%), C. rotundus (7.9%), Radix Aucklandiae (7.9%), and C. Pinnatifida Bunge (7.9%).,, Modern pharmacological researches showed that S. miltiorrhiza Bunge was an excellent slow calcium-channel blocker which could prevent the damage of the membrane's structure and function under the condition of ischemia and hypoxia.L. chuanxiong Hort mainly acts as a calcium antagonist; it can regulate the release of various vasoactive substances and improve the microcirculation. Radix Paeoniae Rubra can expand the blood vessel and increase coronary blood flow.C. tinctorius L is an oxygen-free radical scavenger, which can inhibit platelet aggregation and reduce blood viscosity.C. rotundus and Radix Aucklandiae can reduce blood viscosity and relieve pain., Taken together, these studies suggest that Le-Mai particle works in many ways to cure angina pectoris such as dilating blood vessels and reducing blood viscosity, which is termed as invigorating the circulation of Qi and blood in TCM.
In China, Le-Mai particle has been used to treat angina pectoris for a long time. The government of Canada is ready to launch this TCM on the domestic market. However, so far, no pooled analysis has been performed on the beneficial effects of Le-Mai particle on angina pectoris. Thus, this study provides the first PRISMA-compliant pooled analysis to examine the efficacy and safety of Le-Mai particle. This pooled analysis supports the clinical efficacy of Le-Mai particle in the treatment of angina pectoris, which is consistent with most published RCT findings. Therefore, it is recommended to treat angina pectoris of CHD by using both CWM and Le-Mai particle. However, it is not clear whether the curative effect of Le-Mai single drug is better than that of CWM.
There are several potential limitations in this pooled analysis. First, this pooled analysis only included published RCTs and some negative results may not be published, which may lead to selection bias. Second, the sample size was small, and the duration of intervention was short, which might not be able to provide precise results for the efficacy of Le-Mai particle. Therefore, studies with relatively larger sample sizes and longer duration are needed to accurately verify the efficacy and safety of Le-Mai particle in treating angina pectoris.
| Conclusion|| |
Our study provides preliminary evidence that supports the use of Le-Mai particle as a potentially optimistic and reliable intervention for angina pectoris. Nevertheless, despite our rigorous methodology, the inherent limitations of included studies prevent us from reaching definitive conclusions. Future strictly designed, multi-center, large-scale, and long-term clinical trials are awaited to improve and update the findings of effectiveness and safety of Le-Mai particle for angina pectoris.
Financial support and sponsorship
This work was financially supported by the Natural Science Foundation of Shandong Province (No. ZR2016HQ26 to Z.Z.), the Key Research and Development Plan of Shandong Province (No. 2018GSF118176 to Z.Z. and No. 2018GSF118234 to P.H.), the China Cardiovascular Association-Advanced Research Fund (No. 2018-CCA-AF-004 to P.H.), Cardiac Rehabilitation and Metabolic Therapy Research Fund (to P.H.), the Dyslipidemia and Atherosclerosis Research Fund (No. MSD-2017008 to P.H.), the Bethune-Merck's Diabetes Research Foundation (No: G2016014 to Z.Z. and No: G2018030 to P.H.), and the Clinical Medicine Science and Technology Innovation Plan of Jinan Science and Technology Bureau (No. 201805080 to P.H.).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Peng S, Zhao M, Wan J, Fang Q, Fang D, Li K. The efficacy of trimetazidine on stable angina pectoris: A meta-analysis of randomized clinical trials. Int J Cardiol 2014;177:780-5.
Shao H, Li M, Chen F, Chen L, Jiang Z, Zhao L. The efficacy of Danshen injection as adjunctive therapy in treating angina pectoris: A systematic review and meta-analysis. Heart Lung Circ 2018;27:433-42.
Smith SC Jr., Collins A, Ferrari R, Holmes DR Jr., Logstrup S, McGhie DV, et al.
Our time: A call to save preventable death from cardiovascular disease (heart disease and stroke). J Am Coll Cardiol 2012;60:2343-8.
Aziz A, Hansen HS, Sechtem U, Prescott E, Ong P. Sex-related differences in vasomotor function in patients with angina and unobstructed coronary arteries. J Am Coll Cardiol 2017;70:2349-58.
Yanli B, Guofu H. Epidemiological investigation and prevention of angina pectoris. Cardiovasc Dis J Integr Tradit Chin West Med (Electronic) 2015;3:133-4.
Zhao Y, Yu X, Cao X, Luo L, He L, Mao S, et al.
Cluster analysis for syndromes of real-world coronary heart disease with angina pectoris. Front Med 2018;12:566-71.
Hajizadeh R, Ghaffari S, Ziaee M, Shokouhi B, Separham A, Sarbakhsh P, et al. In vitro
inhibition of platelets aggregation with generic form of clopidogrel versus branded in patients with stable angina pectoris. J Cardiovasc Thorac Res 2017;9:191-5.
Xiao Z, Yujie D, Yang Y. The treatment research of coronary microvascular dysfunction and microvascular angina. Prog Mod Biomed 2016,10:5583-5.
Coylewright M, Dick S, Zmolek B, Askelin J, Hawkins E, Branda M, et al.
PCI choice decision aid for stable coronary artery disease: A randomized trial. Circ Cardiovasc Qual Outcomes 2016;9:767-76.
Zhongyuan W, Hong L, Yongtao Z. Research on the treatment of angina pectoris with traditional Chinese medicine. J Henan Coll Tradit Chin Med 2002;17:79-80.
Hao P, Jiang F, Cheng J, Ma L, Zhang Y, Zhao Y, et al.
Traditional Chinese medicine for cardiovascular disease: Evidence and potential mechanisms. J Am Coll Cardiol 2017;69:2952-66.
Zhiqin L. The clinical curative effect of Le-Mai particle in treating angina pectoris. West China J Pharm Sci 2005;20:569.
Xueliang L. Evaluation of therapeutic effect of Le-mai particle on patients with unstable angina pectoris. Drugs Clin 2013, 9:247-8.
Peng S, Xiaoying M. Treatment of coronary heart disease angina pectoris by Le-Mai particle: 55 cases. West China J Pharm Sci 2002;17:77.
Chunlan W. The clinical observation on the treatment of patients with angina pectoris of coronary heart disease by Le-Mai particle. J Med Res 2009;38:107-8.
Yongchun L. Clinical study on the treatment of angina pectoris with a combination of traditional Chinese and Western medicine. J Clin Exp Med 2007;6:121.
Li L. Retrospective Clinical analysis on treating angina pectoris with combination of traditional Chinese and western medicine. Med Aesthet Beauty 2017;1:37-8.
Huang J, Tang X, Ye F, He J, Kong X. Clinical therapeutic effects of aspirin in combination with Fufang Danshen Diwan, a traditional Chinese medicine formula, on coronary heart disease: A systematic review and meta-analysis. Cell Physiol Biochem 2016;39:1955-63.
Ying X, Junyan Y. Clinical study on treating angina pectoris with integrative medicine. West J Tradit Chin Med 2011;24:76-7.
Bing G. The pharmacological action and clinical application analysis of Danshen. Chin J Mod Drug Appl 2018;1:196-7.
Peixiang Q. Research progress on the pharmacological action of chuanxiong. Nei Mongol J Tradit Chin Med 2011;3:78-9.
Lanxin J, Hao H. Changzhi L. Research progress on pharmacological action of red peony. Drug Eval Res 2010;3:233-6.
Lina G, Yuanlu C, Kuo Y. The research progress on compatibility of danshen and safflower. Chin Tradit Herb Drugs 2016;4:671-9.
Cunlu L. An overview of angina pectoris treated with TCM in clinical research. Clin J Chin Med 2010;2:29-33.
Minhua T. Summary of TCM treatment in angina pectoris. Asia Pac Tradit Med 2014;10:52-3.
[Table 1], [Table 2]