Is danshen (Salvia miltiorrhiza) dripping pill more effective than isosorbide dinitrate in treating angina pectoris? A systematic review of randomized controlled trials
Introduction
Danshen dripping pill (DSP) is composed of Salvia miltiorrhiza (danshen), Panax notoginseng, and Dryobalanops camphor [1]. Danshen and its active compounds tanshinones and isotanshinones have bioactivities against myocardial ischemia, inflammation, and angiotensin converting enzyme [2]. In 2008, the global market of DSP was about 1.4 billion RMB (equivalent to 205 million USD), ranked topmost in market share among all Chinese medicinal over-the-counter drugs [3]. DSP is the most popular Chinese medicinal product in China for treating coronary heart disease [4], which is routinely treated by isosorbide dinitrate (ISDN) in orthodox medicine [5].
The term “coronary heart disease” is synonymous with the term “ischemic heart disease” [6]. Ischemic heart disease is defined as myocardial impairment due to an imbalance coronary blood flow and myocardial requirement caused by changes in the coronary circulation [6]. In this disease, angina pectoris, i.e. severe chest pain, usually occurs [7] and causes most sudden deaths [8]. Ischemic heart disease is usually diagnosed by clinical examinations of symptoms and ECG [6].
As the first Chinese medicinal product listed as an investigational new drug (IND No. 56956) by the United States Food and Drug Administration (FDA) in 1997, DSP has been extensively tested by various forms of clinical trials. The efficacy of DSP is still not recognized worldwide even after more than 100 reports of randomized controlled trials (RCT) have been published in China. It is difficult to accept the efficacy of DSP because most of the published Chinese reports are inaccessible to international researchers and their compliance with the current CONSORT 2010 [9] is unknown.
According to the PRISMA statement [10], the currently available four systematic reviews on DSP [11], [13], [14], [15] are inadequate in systematic reviewing. The first systematic review [11] included 22 RCTs published in 1997–2002. The quality of RCTs, although assessed in Jadad scale [12], was not considered for eligibility. Its only sensitivity analysis was a simple comparison of the overall effects using fixed-effect model and random-effects model. Two systematic reviews [13], [14] respectively covered 34 studies (published in 2002–2007) and 33 studies (published in 1997–2006) including both randomized and non-randomized controlled trials. No sensitivity or subgroup analysis was performed. The latest Chinese systematic review [15] included only 10 RCTs between 2003 and 2008. In these four systematic reviews, DSP and ISDN were used with other anti-anginal drugs. The manufacturer recommended dosages and treatment durations were not followed. As such, the efficacy of DSP could not be properly evaluated. Many eligible RCTs were missed from previous systematic reviews because of weak search strategies. All of the previous systematic reviews do not comply with the PRISMA statement [10]. Therefore, it is necessary to have a more comprehensive, updated, and PRISMA-compliant systematic review. This article aims to provide a comprehensive, PRISMA-compliant, internationally accessible, and timely systematic review, with sensitivity and subgroup analyses, of RCTs on comparing DSP with ISDN in treating angina pectoris.
Section snippets
Eligibility criteria for study selection
Randomized controlled trials published between 1994 (i.e., year of DSP launch) and 2009 on comparing DSP with ISDN in treating angina pectoris were screened and filtered. Specific inclusion criteria were used to select those studies in which (a) RCT designs were explicitly described; (b) DSP was used as the experimental and ISDN was used as the control; (c) duration of treatment (follow-up period) was at least 4 weeks; (d) participants were suffering from angina pectoris as diagnosed by the
Study selection
The process of study selection was depicted in Fig. 1. The search of the PubMed, CNKI, WangFang Data, Chinese Electronic Periodical Services, and China Master Theses Full-text Database identified 26, 659, 292, 43, and 1 articles, respectively. After adding relevant articles cited in review articles [11], [13], [14], [15], [20], total 1103 articles were subject to manual screening based on titles and abstracts. Six hundred and ninety-nine non-clinical trials were excluded. One hundred and
Discussion
This article provides a PRISMA-compliant and internationally accessible systematic review, especially to those who cannot access Chinese RCT reports, on the efficacy of danshen dripping pill (DSP). The meta-analysis of the eligible 60 RCTs shows a consistent result that DSP might be more effective than isosorbide dinitrate (ISDN) in treating angina pectoris at overall odds ratios around 2 with statistical significance (P < 0.00001). Publication bias was not found to be significant. Sensitivity
Conclusion
The 60 eligible RCTs indicate that DSP is apparently more effective than ISDN in treating angina pectoris. However, further RCTs of larger scale, multi-centre/country, longer follow-up periods, and higher quality are still required to verify the efficacy of DSP over all anti-anginal therapies.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
Y.J. and S.L. designed this study including search strategy, eligibility criteria, and meta-analysis, sensitivity analysis, and subgroup analysis. Y.J. and S.L. selected studies and analyzed the data. S.Z. and F.H. checked and repeated the data analysis. S.L. and Y.J. wrote the manuscript. All authors read and approved the final manuscript.
The following are the supplementary materials related to this article.
Acknowledgements
The work of SL in this project was partially supported by the e-Science Research Theme 2009–2010 grant received from the National e-Science Institute, United Kingdom. The work of Y.L. in this project received the Sanhome Pharmaceutical Cup (First Prize) in China. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [91].
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