Efficacy of Sodium Tanshinone IIA Sulfonate in Patients with Non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Results from a Multicentre, Controlled, Randomized Trial



Sodium tanshinone IIA sulfonate (STS) has been widely used by Chinese medicine practitioners for chronic cardiovascular diseases. However, its direct clinical efficacy in patients with acute coronary syndrome following percutaneous coronary intervention (PCI) has not been reported yet. The present trial aimed to investigate potential cardioprotection of STS in patients undergoing PCI for non-ST elevation acute coronary syndrome (NSTE-ACS).


In a randomized, double-blind, placebo-controlled trial, 372 patients with NSTE-ACS were randomly assigned to receive STS (n = 192) or saline (n = 180) for 2 days before and 3 days after PCI along with standard therapy. The primary endpoint was the composite incidence of major adverse cardiac events (MACEs), including death, non-fatal myocardial infarction, repeated revascularization of the target vessel, and stent thrombosis, within 30 days after PCI.


The 30-day MACEs occurred in 18.8% of the patients in the STS group and in 27.2% of the patients in the control group (P = 0.038); this difference was mostly driven by reduction of myocardial infarction incidence (17.2% vs. 26.7%, P = 0.027). Post-procedural elevation of troponin-I was also significantly lower in the STS group (26.56% vs. 47.78%, P < 0.001). Multivariable analysis identified STS as a predictor of decreased risk of MACE occurrence (odds ratio: 0.60, 95% confidence interval: 0.36 to 0.99; P = 0.045).


Addition of STS to the standard treatments recommended by the current practice guidelines in patients with NSTE-ACS undergoing PCI could reduce myocardial injury and the occurrence of short-term cardiovascular events, primarily driven by non-fatal myocardial infarction.

Trial Registration


This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3



Acute coronary syndrome


Adverse event


Data and safety monitoring board


High-sensitive C-reactive protein


Major adverse cardiovascular event


non-ST segment elevation acute coronary syndrome


Non-ST elevation myocardial infarction


Myocardial infarction


Odds ratios


Percutaneous coronary intervention


Periprocedural myocardial injury


ST-segment elevation acute coronary syndrome


sodium tanshinone IIA sulfonate group


Thrombolysis in myocardial infarction


Upper reference limit


  1. 1.

    Sarma AA, Braunwald E, Cannon CP, Guo J, Im K, Antman EM, et al. Outcomes of women compared with men after non-ST-segment elevation acute coronary syndromes. J Am Coll Cardiol. 2019;74(24):3013–22.

    Article  CAS  Google Scholar 

  2. 2.

    Li Y, Pei H, Bulluck H, Zhou C, Hausenloy DJ. Periprocedural elevated myocardial biomarkers and clinical outcomes following elective percutaneous coronary intervention: a comprehensive dose-response meta-analysis of 44,972 patients from 24 prospective studies. EuroIntervention. 2020;15(16):1444–50.

    Article  Google Scholar 

  3. 3.

    Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018;72(18):2231–64.

    Article  Google Scholar 

  4. 4.

    Soud M, Hideo-Kajita A, Ho G, Yacob O, Alahdab F, King F, et al. Impact of periprocedural biomarker elevation on mortality in stable angina pectoris patients undergoing elective coronary intervention: a systematic review and meta-analysis including 24 666 patients. Coron Artery Dis. 2020;31(2):137–46.

    Article  Google Scholar 

  5. 5.

    Li J, Li X, Wang Q, Hu S, Wang Y, Masoudi FA, et al. ST-segment elevation myocardial infarction in China from 2001 to 2011 (the China PEACE-Retrospective Acute Myocardial Infarction Study): a retrospective analysis of hospital data. Lancet. 2015;385(9966):441–51.

    Article  Google Scholar 

  6. 6.

    Patti G, Pasceri V, Colonna G, Miglionico M, Fischetti D, Sardella G, et al. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. J Am Coll Cardiol. 2007;49(12):1272–8.

    Article  CAS  Google Scholar 

  7. 7.

    Patti G, Nusca A, Chello M, Pasceri V, D'Ambrosio A, Vetrovec GW, et al. Usefulness of statin pretreatment to prevent contrast-induced nephropathy and to improve long-term outcome in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2008;101(3):279–85.

    Article  CAS  Google Scholar 

  8. 8.

    Jang Y, Zhu J, Ge J, Kim YJ, Ji C, Lam W. Preloading with atorvastatin before percutaneous coronary intervention in statin-naive Asian patients with non-ST elevation acute coronary syndromes: a randomized study. J Cardiol. 2014;63(5):335–43.

    Article  Google Scholar 

  9. 9.

    Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532–61.

    Article  CAS  Google Scholar 

  10. 10.

    Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. Jama. 2011;305(24):2556–64.

    Article  CAS  Google Scholar 

  11. 11.

    Kim DD, Sanchez FA, Duran RG, Kanetaka T, Duran WN. Endothelial nitric oxide synthase is a molecular vascular target for the Chinese herb Danshen in hypertension. Am J Physiol Heart Circ Physiol. 2007;292(5):H2131–7.

    Article  CAS  Google Scholar 

  12. 12.

    Tang C, Wu AH, Xue HL, Wang YJ. Tanshinone IIA inhibits endothelin-1 production in TNF-alpha-induced brain microvascular endothelial cells through suppression of endothelin-converting enzyme-1 synthesis. Acta Pharmacol Sin. 2007;28(8):1116–22.

    Article  CAS  Google Scholar 

  13. 13.

    Qiu X, Miles A, Jiang X, Sun X, Yang N. Sulfotanshinone sodium injection for unstable angina pectoris: a systematic review of randomized controlled trials. Evid Based Complement Alternat Med. 2012;2012:715790.

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Long R, You Y, Li W, Jin N, Huang S, Li T, et al. Sodium tanshinone IIA sulfonate ameliorates experimental coronary no-reflow phenomenon through down-regulation of FGL2. Life Sci. 2015;142:8–18.

    Article  CAS  Google Scholar 

  15. 15.

    Mao S, Vincent M, Chen M, Zhang M, Hinek A. Exploration of multiple signaling pathways through which sodium tanshinone IIA sulfonate attenuates pathologic remodeling experimental infarction. Front Pharmacol. 2019;10:779.

    Article  CAS  Google Scholar 

  16. 16.

    Mao S, Wang L, Zhao X, Shang H, Zhang M, Hinek A. Sodium tanshinone IIA sulfonate for reduction of periprocedural myocardial injury during percutaneous coronary intervention (STAMP trial): rationale and design. Int J Cardiol. 2015;182:329–33.

    Article  Google Scholar 

  17. 17.

    Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124(23):e574–651.

    PubMed  Google Scholar 

  18. 18.

    Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, et al. 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61(23):e179–347.

    Article  Google Scholar 

  19. 19.

    Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60(16):1581–98.

    Article  Google Scholar 

  20. 20.

    Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123(23):2736–47.

    Article  Google Scholar 

  21. 21.

    Porto I, Selvanayagam JB, Van Gaal WJ, Prati F, Cheng A, Channon K, et al. Plaque volume and occurrence and location of periprocedural myocardial necrosis after percutaneous coronary intervention: insights from delayed-enhancement magnetic resonance imaging, thrombolysis in myocardial infarction myocardial perfusion grade analysis, and intravascular ultrasound. Circulation. 2006;114(7):662–9.

    Article  Google Scholar 

  22. 22.

    Mao S, Taylor S, Chen Q, Zhang M, Hinek A. Sodium tanshinone IIA sulfonate prevents the adverse left ventricular remodelling: focus on polymorphonuclear neutrophil-derived granule components. J Cell Mol Med. 2019;23(7):4592–600.

    PubMed  PubMed Central  CAS  Google Scholar 

  23. 23.

    Cheng Q, Zhao Y, Li J. Sodium tanshinone IIA sulfonate suppresses heat stress-induced endothelial cell apoptosis by promoting NO production through upregulating the PI3K/AKT/eNOS pathway. Mol Med Rep. 2017;16(2):1612–8.

    Article  CAS  Google Scholar 

  24. 24.

    Zhang W, He H, Liu J, Wang J, Zhang S, Zhang S, et al. Pharmacokinetics and atherosclerotic lesions targeting effects of tanshinone IIA discoidal and spherical biomimetic high density lipoproteins. Biomaterials. 2013;34(1):306–19.

    Article  CAS  Google Scholar 

  25. 25.

    Maione F, Cantone V, Chini MG, De Feo V, Mascolo N, Bifulco G. Molecular mechanism of tanshinone IIA and cryptotanshinone in platelet anti-aggregating effects: an integrated study of pharmacology and computational analysis. Fitoterapia. 2015;100:174–8.

    Article  CAS  Google Scholar 

  26. 26.

    Maione F, De Feo V, Caiazzo E, De Martino L, Cicala C, Mascolo N. Tanshinone IIA, a major component of Salvia milthorriza Bunge, inhibits platelet activation via Erk-2 signaling pathway. J Ethnopharmacol. 2014;155(2):1236–42.

    Article  CAS  Google Scholar 

  27. 27.

    Wu LC, Lin X, Sun H. Tanshinone IIA protects rabbits against LPS-induced disseminated intravascular coagulation (DIC). Acta Pharmacol Sin. 2012;33(10):1254–9.

    Article  CAS  Google Scholar 

  28. 28.

    Hu Q, Wei B, Wei L, Hua K, Yu X, Li H, et al. Sodium tanshinone IIA sulfonate ameliorates ischemia-induced myocardial inflammation and lipid accumulation in Beagle dogs through NLRP3 inflammasome. Int J Cardiol. 2015;196:183–92.

    Article  Google Scholar 

  29. 29.

    Zhang H, Long M, Wu Z, Han X, Yu Y. Sodium tanshinone IIA silate as an add-on therapy in patients with unstable angina pectoris. J Thorac Disease. 2014;6(12):1794–9.

    Google Scholar 

  30. 30.

    Chan TY. Interaction between warfarin and danshen (Salvia miltiorrhiza). Ann Pharmacother. 2001;35(4):501–4.

    Article  CAS  Google Scholar 

Download references


The authors gratefully acknowledge the contributions of all staff for their participation in the STAMP study.


This study was funded by the National Science Foundation (No. 81703877& 81703848), a Featured Innovative Project from Guangdong Provincial Universities (2019KTSCX029), Young Talents Support Project from the China Association of Chinese Medicine (2019-QNRC2-C06), the Youth Talent Development Program from Guangzhou University of Chinese Medicine (to Shuai MAO), and the Team for the prevention and treatment of acute myocardial infarction with Chinese medicine (2019KCXTD009). The sponsors had no role in project development, the collection of data, or the preparation of this manuscript, nor the decision to publish.

Author information




S.M. drafted this manuscript; L.H.G. and M.Z.Z. designed the described study; X.J.Z. and Z.L. completed the statistical analysis; H.C.S. designed the randomization and concealment for this study; S.M., X.J.Z., Q.L., X.F.W., X.H.D. performed the study; A.H. contributed to the interpretation of the data and made critical revision of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Minzhou Zhang.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material


(DOCX 22 kb)


(JPG 24 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mao, S., Wang, L., Zhao, X. et al. Efficacy of Sodium Tanshinone IIA Sulfonate in Patients with Non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Results from a Multicentre, Controlled, Randomized Trial. Cardiovasc Drugs Ther (2020). https://doi.org/10.1007/s10557-020-07077-8

Download citation


  • Sodium tanshinone IIA sulfonate
  • Periprocedural myocardial infarction
  • Non-ST segment elevation acute coronary syndrome
  • Percutaneous coronary intervention