Efficacy and safety of Shexiang Baoxin pill (MUSKARDIA) in patients with stable coronary artery disease: a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial

Supplemental Digital Content is available in the text Abstract Background: The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD. Methods: A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency. Results: In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45–1.07; P = 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785). Conclusions: As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD. Trial registration chictr.org.cn, No. ChiCTR-TRC-12003513

[1]  J. Bosch,et al.  Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. , 2018, Lancet.

[2]  X. Xie,et al.  The efficacy and safety of cilostazol as an alternative to aspirin in Chinese patients with aspirin intolerance after coronary stent implantation: a combined clinical study and computational system pharmacology analysis , 2017, Acta Pharmacologica Sinica.

[3]  Chau-Chung Wu,et al.  Residual Risk Factors to Predict Major Adverse Cardiovascular Events in Atherosclerotic Cardiovascular Disease Patients with and without Diabetes Mellitus , 2017, Scientific Reports.

[4]  Anushka Patel,et al.  Six-month adherence to Statin use and subsequent risk of major adverse cardiovascular events (MACE) in patients discharged with acute coronary syndromes , 2017, Lipids in Health and Disease.

[5]  Guo-Qing Zheng,et al.  Shexiang Baoxin Pills for Coronary Heart Disease in Animal Models: Preclinical Evidence and Promoting Angiogenesis Mechanism , 2017, Front. Pharmacol..

[6]  Y. Zhang,et al.  Traditional Chinese Medicine for Cardiovascular Disease: Evidence and Potential Mechanisms , 2017, Deutsche Zeitschrift für Akupunktur.

[7]  Xing Chen,et al.  A network-based method for mechanistic investigation of Shexiang Baoxin Pill’s treatment of cardiovascular diseases , 2017, Scientific Reports.

[8]  S. Adisakwattana.  Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications , 2017, Nutrients.

[9]  W. Shen,et al.  A Chinese patent medicine, Shexiang Baoxin Pill, for Non-ST-elevation acute coronary syndromes: A systematic review. , 2016, Journal of ethnopharmacology.

[10]  G. Francis,et al.  2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. , 2016, The Canadian journal of cardiology.

[11]  Jie Wang,et al.  Cardiovascular Disease, Mitochondria, and Traditional Chinese Medicine , 2015, Evidence-based complementary and alternative medicine : eCAM.

[12]  Weidong Zhang,et al.  Simultaneous determination of seven bufadienolides in rat plasma after oral administration of Shexiang Baoxin Pill by liquid chromatography-electrospray ionization-tandem mass spectrometry: application to a pharmacokinetic study. , 2014, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[13]  Weidong Zhang,et al.  Simultaneous determination of four volatile compounds in rat plasma after oral administration of Shexiang Baoxin Pill (SBP) by HS-SPDE-GC-MS/MS and its application to pharmacokinetic studies. , 2014, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[14]  Zhijian Yang,et al.  Beneficial effects of muscone on cardiac remodeling in a mouse model of myocardial infarction , 2014, International journal of molecular medicine.

[15]  B. Gersh,et al.  Comparison of outcomes in patients with ST-segment elevation myocardial infarction discharged on versus not on statin therapy (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial). , 2014, The American journal of cardiology.

[16]  Jong-Hoon Kim,et al.  A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases , 2014, Journal of ginseng research.

[17]  X. Chu,et al.  Study on the anti-cerebral ischemia effect of borneol and its mechanism. , 2013, African journal of traditional, complementary, and alternative medicines : AJTCAM.

[18]  G. De Backer,et al.  Residual risk of cardiovascular mortality in patients with coronary heart disease: the EUROASPIRE risk categories. , 2013, International journal of cardiology.

[19]  A. Colombo,et al.  Aspirin intolerance and the need for dual antiplatelet therapy after stent implantation: a proposed alternative regimen. , 2013, International journal of cardiology.

[20]  Geng Xu,et al.  Aspirin-exacerbated respiratory disease in China: A cohort investigation and literature review , 2012, American journal of rhinology & allergy.

[21]  John Spertus,et al.  AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. , 2011, Circulation.

[22]  R. Collins,et al.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials , 2010, The Lancet.

[23]  M. Gnant,et al.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials , 2010 .

[24]  Deepak L. Bhatt,et al.  Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. , 2010, JAMA.

[25]  G. Boysen,et al.  European Guidelines on Cardiovascular Disease Prevention , 2009, International journal of stroke : official journal of the International Stroke Society.

[26]  Yong Wang,et al.  [Evaluation on tolerability and safety of long-term administration with shexiang baoxin pill in patients with coronary heart disease of stable angina pectoris]. , 2008, Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine.

[27]  T. Fahey,et al.  Adherence to statin or aspirin or both in patients with established cardiovascular disease: exploring healthy behaviour vs. drug effects and 10-year follow-up of outcome , 2008, British journal of clinical pharmacology.

[28]  T. Kurata,et al.  Therapy with statins and aspirin enhances long-term outcome of percutaneous coronary intervention , 2008, Heart and Vessels.

[29]  J. Tijssen,et al.  Long-term outcome after an early invasive versus selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome and elevated cardiac troponin T (the ICTUS trial): a follow-up study , 2007, The Lancet.

[30]  D. Alter,et al.  Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. , 2007, JAMA.

[31]  F. Van de Werf,et al.  Patients using statin treatment within 24 h after admission for ST-elevation acute coronary syndromes had lower mortality than non-users: a report from the first Euro Heart Survey on acute coronary syndromes. , 2006, European heart journal.

[32]  P. Poole‐Wilson,et al.  Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial , 2004, The Lancet.

[33]  D. Hoffmann.  Medical Herbalism: The Science and Practice of Herbal Medicine , 2003 .

[34]  T. Lam.  Strengths and weaknesses of traditional Chinese medicine and Western medicine in the eyes of some Hong Kong Chinese , 2001, Journal of epidemiology and community health.

[35]  Michael F. Oliver,et al.  Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study. , 2001, Indian heart journal.

[36]  L. Wallentin,et al.  Early statin treatment following acute myocardial infarction and 1-year survival. , 2001, JAMA.

[37]  M. Simoons,et al.  The European trial on reduction of cardiac events with perindopril in stable coronary artery disease (EUROPA). , 1998, European heart journal.

[38]  D. Berman,et al.  Effects of cardiac medications for patients with obstructive coronary artery disease by coronary computed tomographic angiography: results from the multicenter CONFIRM registry. , 2015, Atherosclerosis.

[39]  A. Hoes,et al.  [Guidelines on cardiovascular disease prevention in clinical practice]. , 2005, Revue medicale de Liege.