Skip to main content
SpringerLink
Log in

Pharmacodynamic effects of indobufen compared with aspirin in patients with coronary atherosclerosis

  • Clinical Trial
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

This study aimed to investigate the pharmacodynamic effects of indobufen and low-dose aspirin in patients with coronary atherosclerosis.

Methods

In the first phase, 218 patients with coronary atherosclerosis were randomly assigned to receive aspirin 100 mg once daily (standard dose); 100 mg once every 2 days; 100 mg once every 3 days; 50 mg twice daily; 75 mg once daily; 50 mg once daily; or indobufen 100 mg twice daily for 1 month. In the second phase, 20 healthy subjects were treated with indobufen 100 mg twice daily for 1 week followed after a 2-week washout by aspirin 100 mg once daily for 1 week. The primary outcome was arachidonic acid-induced platelet aggregation (PLAA), and the secondary outcomes included plasma thromboxane B2 (TXB2) and urinary 11-dehydro-TXB2 (11-dh-TXB2) levels at the end of each treatment. 

Results

In the first phase, compared with aspirin 100 mg once daily: all aspirin groups had similar suppression of PLAA whereas indobufen group had significantly less suppressed PLAA. Aspirin given every second or third day, and indobufen produced less suppression of plasma TXB2. All treatment regimens produced similar inhibition of 11-dh-TXB2. In the second phase, compared with aspirin, indobufen produced less suppression of plasma TXB2 at 8 h and 12 h after the last dose.

Conclusions

Aspirin 50 mg twice daily, 75 mg once daily, and aspirin 50 mg once daily produce antiplatelet effects that are similar to aspirin 100 mg once daily. Aspirin given less often than once daily and indobufen 100 mg twice daily do not suppress platelets as effectively as aspirin 100 mg once daily.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Munoz D, Smith SC Jr, Virani SS, Williams KA Sr, Yeboah J, Ziaeian B (2019) 2019 ACC/AHA Guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation 140(11):e596–e646. https://doi.org/10.1161/CIR.0000000000000678

    Article  PubMed  PubMed Central  Google Scholar 

  2. Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Juni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferovic PM, Sibbing D, Stefanini GG, Windecker S, Yadav R, Zembala MO, Group ESCSD (2019) 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 40(2):87–165. https://doi.org/10.1093/eurheartj/ehy394

    Article  Google Scholar 

  3. Capodanno D, Alfonso F, Levine GN, Valgimigli M, Angiolillo DJ (2018) ACC/AHA versus ESC guidelines on dual antiplatelet therapy: JACC Guideline Comparison. J Am Coll Cardiol 72 (23 Pt A): 2915–2931. https://doi.org/10.1016/j.jacc.2018.09.057

  4. Binderup HG, Houlind K, Brasen CL, Madsen JS (2019) Identification of aspirin resistance using a PDW-miR92a-score: Validation in an intermittent claudication cohort. Clin Biochem 64:30–36. https://doi.org/10.1016/j.clinbiochem.2018.12.009

    Article  CAS  Google Scholar 

  5.  Schrör K (1997) Aspirin and platelets: the antiplatelet action of aspirin and its role in thrombosis treatment and prophylaxis. Semin Thromb Hemost 23(4):349–356. https://doi.org/10.1055/s-2007-996108

    Article  Google Scholar 

  6. Group ASC, Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, Murphy K, Aung T, Haynes R, Cox J, Murawska A, Young A, Lay M, Chen F, Sammons E, Waters E, Adler A, Bodansky J, Farmer A, McPherson R, Neil A, Simpson D, Peto R, Baigent C, Collins R, Parish S, Armitage J (2018) Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 379(16):1529–1539. https://doi.org/10.1056/NEJMoa1804988

    Article  Google Scholar 

  7. Laheij RJ, Jansen JB, Verbeek AL, Verheugt FW (2001) Helicobacter pylori infection as a risk factor for gastrointestinal symptoms in patients using aspirin to prevent ischaemic heart disease. Aliment Pharmacol Ther 15(7):1055–1059. https://doi.org/10.1046/j.1365-2036.2001.01016.x

    Article  Google Scholar 

  8. Devillier P (2001) [Pharmacology of non-steroidal anti-inflammatory drugs and ENT pathology]. Presse medicale (Paris, France : 1983) 30(39-40 Pt 2):70–79

  9. Liu J, Xu D, Xia N, Hou K, Chen S, Wang Y, Li Y (2018) Anticoagulant activities of indobufen, an antiplatelet drug. Molecules (Basel, Switzerland) 23(6):1452. https://doi.org/10.3390/molecules23061452

  10. Barillà F, Pulcinelli FM, Mangieri E, Torromeo C, Tanzilli G, Dominici T, Pellicano M, Paravati V, Acconcia MC, Gaudio C (2013) Clopidogrel plus indobufen in acute coronary syndrome patients with hypersensitivity to aspirin undergoing percutaneous coronary intervention. Platelets 24(3):183–188. https://doi.org/10.3109/09537104.2012.686072

    Article  Google Scholar 

  11. Marzo A, Crestani S, Fumagalli I, Giusti A, Lowenthal DT (2004) Endoscopic evaluation of the effects of indobufen and aspirin in healthy volunteers. Am J Ther 11(2):98–102. https://doi.org/10.1097/00045391-200403000-00004

    Article  Google Scholar 

  12. Task Force on Chinese Guidelines for the Prevention of Cardiovascular D, Editorial Board of Chinese Journal of C, (2018) [Chinese guidelines for the prevention of cardiovascular diseases(2017)]. Zhonghua Xin Xue Guan Bing Za Zhi 46(1):10–25. https://doi.org/10.3760/cma.j.issn.0253-3758.2018.01.004

    Article  Google Scholar 

  13. Saw J, Madsen EH, Chan S, Maurer-Spurej E (2008) The ELAPSE (evaluation of long-term clopidogrel antiplatelet and systemic anti-inflammatory effects) study. J Am Coll Cardiol 52(23):1826–1833. https://doi.org/10.1016/j.jacc.2008.08.047

    Article  Google Scholar 

  14. Li C, Hirsh J, Xie C, Johnston MA, Eikelboom JW (2012) Reversal of the anti-platelet effects of aspirin and clopidogrel. J Thromb Haemost 10(4):521–528. https://doi.org/10.1111/j.1538-7836.2012.04641.x

    Article  CAS  PubMed  Google Scholar 

  15. Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H (2011) Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 123(23):2736–2747. https://doi.org/10.1161/circulationaha.110.009449

    Article  PubMed  Google Scholar 

  16. Eikelboom J, Hirsh J, Weitz J, Johnston M, Yi Q, Yusuf S (2002) Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 105(14):1650–1655. https://doi.org/10.1161/01.cir.0000013777.21160.07

    Article  CAS  PubMed  Google Scholar 

  17. Morocutti C, Amabile G, Fattapposta F, Nicolosi A, Matteoli S, Trappolini M, Cataldo G, Milanesi G, Lavezzari M, Pamparana F, Coccheri S (1997) Indobufen versus warfarin in the secondary prevention of major vascular events in nonrheumatic atrial fibrillation. SIFA (Studio Italiano Fibrillazione Atriale) Investigators. Stroke 28(5):1015-1021. https://doi.org/10.1161/01.str.28.5.1015

  18. Catella F, Healy D, Lawson J, FitzGerald G (1986) 11-Dehydrothromboxane B2: a quantitative index of thromboxane A2 formation in the human circulation. Proc Natl Acad Sci USA 83(16):5861–5865. https://doi.org/10.1073/pnas.83.16.5861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Harrison P, Frelinger A, Furman M, Michelson A (2007) Measuring antiplatelet drug effects in the laboratory. Thromb Res 120(3):323–336. https://doi.org/10.1016/j.thromres.2006.11.012

    Article  CAS  PubMed  Google Scholar 

  20. Liu T, Zhang J, Chen Y, Feng X, Wang L, Liu M (2015) ASSA14-03-38 Comparison of urinary11-dehydrothromboxaneB2 detection and plasma LTA assay for evaluating aspirin response in the Aged Patients with Coronary Artery Disease. Heart 101(Suppl 1):A22–A22. https://doi.org/10.1136/heartjnl-2014-307109.56

    Article  Google Scholar 

  21. Fan L, Cao J, Liu L, Li X, Hu G, Hu Y, Zhu B (2013) Frequency, risk factors, prognosis, and genetic polymorphism of the cyclooxygenase-1 gene for aspirin resistance in elderly Chinese patients with cardiovascular disease. Gerontology 59(2):122–131. https://doi.org/10.1159/000342489

    Article  CAS  PubMed  Google Scholar 

  22. Pastori D, Nocella C, Farcomeni A, Bartimoccia S, Santulli M, Vasaturo F, Carnevale R, Menichelli D, Violi F, Pignatelli P (2017) Relationship of PCSK9 and urinary thromboxane excretion to cardiovascular events in patients with atrial fibrillation. J Am Coll Cardiol 70(12):1455–1462. https://doi.org/10.1016/j.jacc.2017.07.743

    Article  Google Scholar 

  23. Lee JY, Sung KC, Choi HI (2016) Comparison of aspirin and indobufen in healthy volunteers. Platelets 27(2):105–109. https://doi.org/10.3109/09537104.2015.1042853

    Google Scholar 

  24. Cipollone F, Patrignani P, Greco A, Panara M, Padovano R, Cuccurullo F, Patrono C, Rebuzzi A, Liuzzo G, Quaranta G, Maseri A (1997) Differential suppression of thromboxane biosynthesis by indobufen and aspirin in patients with unstable angina. Circulation 96(4):1109–1116. https://doi.org/10.1161/01.cir.96.4.1109

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by grants from the Jiangsu Province’s Key Provincial Talents Program (ZDRCA2016013), the Second Level of 333 High Level Talent Training Project in Jiangsu Province (BRA2019099), the Nanjing Science and Technology Development Plan 2016 (201605071), the Special Fund for Key R & D Plans (Social Development) of Jiangsu Province (BE2019754), and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD).

Author information

Author notes

  1. Mingwen Yang, Zekang Ye, Lianlian Mei, Inam Ullah are contributed equally to this work.

Authors and Affiliations

  1. Departments of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

    Mingwen Yang, Zekang Ye, Lianlian Mei, Inam Ullah, Chuchu Tan, Guoyu Wang, Qian Gu, Yi Lu, Samee Abdus, Lu Shi, Xiaoxuan Gong & Chunjian Li

  2. Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China

    Jianling Bai

  3. Department of Medicine, McMaster University, Hamilton, Ontario, Canada

    John W. Eikelboom

  4. Thrombosis Service, Hamilton General Hospital, Hamilton, Ontario, Canada

    John W. Eikelboom

Authors
  1. Mingwen Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zekang Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lianlian Mei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Inam Ullah
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chuchu Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guoyu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qian Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yi Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Samee Abdus
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lu Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xiaoxuan Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jianling Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. John W. Eikelboom
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Chunjian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Mingwen Yang, Lianlian Mei, and Chunjian Li designed the study. Mingwen Yang, Lianlian Mei, Zekang Ye, and Inam Ullah performed experiments. Chuchu Tan, Guoyu Wang, Qian Gu, Yi Lu, and Jianling Bai analyzed the data. Samee Abdus, Lu Shi, and Xiaoxuan Gong discussed the results. Mingwen Yang wrote the original manuscript. John W Eikelboom and Chunjian Li reviewed and edited the manuscript.

Corresponding author

Correspondence to Chunjian Li.

Ethics declarations

Ethics approval

This study was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Approval Number2017-SR-226).

Consent to participate

All enrolled subjects signed the informed consent form (ICF) before the study was conducted.

Consent for publication

All co-authors have reviewed and approved this manuscript for publication.

Conflict of interest

Dr. Chunjian Li received the donation of indobufen from Huadong Medicine Co., Ltd., China.

Additional information

Publisher's Note

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

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, M., Ye, Z., Mei, L. et al. Pharmacodynamic effects of indobufen compared with aspirin in patients with coronary atherosclerosis. Eur J Clin Pharmacol 77, 1815–1823 (2021). https://doi.org/10.1007/s00228-021-03177-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-021-03177-y

Keywords

Search

Navigation