Skip to main content
SpringerLink
Log in

Comparison of the antiplatelet effect of clopidogrel hydrogenosulfate and clopidogrel besylate in patients with stable coronary artery disease

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

It is well known that patients with poor response to antiplatelet therapy are most likely to have more thrombotic events. Clopidogrel hydrogensulfate (CHS) is a thienopyridine acting as an important antiplatelet agent alone or in combination with acetylsalicylic acid to prevent cardiovascular complications. A different clopidogrel salt, clopidogrel besylate (CB), was recently approved as a generic drug for the same purpose while data about its antiplatelet effect are very scarce. Our study compared the antiplatelet effect of CHS and CB in patients with stable coronary artery disease. Patients with stable coronary artery disease (n = 101) (coronary lesions defined angiographically 30–70 %) were randomized to either CHS (n = 50) or CB (n = 51). After randomization a 600 mg loading dose of the drug was given and monitoring of antiplatelet effect was done 12–14 h later with VerifyNow assay. Antiplatelet response was measured with P2Y12 reaction units (PRU) and % inhibition P2Y12 from baseline (% inhibition P2Y12). Moreover CYP2C19*2, CYP2C19*3 and CYP3Α5 polymorphisms were studied in all patients. Clinical characteristics were similar between the two study groups. No significant difference was observed for baseline platelet reactivity between CHS and CB patients (258 ± 38 vs. 256 ± 38 respectively, p = 0.79). No difference was found for antiplatelet response between the CHS and the CB group, assessed by PRU (195 ± 74 vs. 204 ± 67 respectively, p = 0.51) and by % inhibition P2Y12 (24 ± 25 vs. 24 ± 22 % respectively, p = 0.95). Number of heterozygotes for CYP2C19*2 polymorphism was comparable and their platelet reactivity was similar between the two study groups. Our results indicate that both CB and CHS had an identical antiplatelet effect in patients with stable coronary artery disease. No difference on platelet reactivity of heterozygotes for CYP2C19*2 polymorphism was found between the two study groups.

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

Similar content being viewed by others

References

  1. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK, Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators (2001) Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 345(7):494–502

    Article  CAS  PubMed  Google Scholar 

  2. Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD, Granger CB, Faxon DP, Rupprecht HJ, Budaj A, Avezum A, Widimsky P, Steg PG, Bassand JP, Montalescot G, Macaya C, Di Pasquale G, Niemela K, Ajani AE, White HD, Chrolavicius S, Gao P, Fox KA, Yusuf S, CURRENT-OASIS 7 trial investigators (2010) Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet 376(9748):1233–1243

    Article  CAS  PubMed  Google Scholar 

  3. Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, Wilmer C, Topol EJ, CREDO Investigators. Clopidogrel for the Reduction of Events During Observation (2002) Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 288(19):2411–2420

    Article  CAS  PubMed  Google Scholar 

  4. Baumgärtel C, Godman B, Malmstrom R, Andersen M, Abuelkhair M, Abdu S, Bennie M, Bishop, Burkhardt T, Furst J, Garuoliene C, Herholz H, Kalaba M, Koskinen H, Laius O, Lonsdale J, Malinowska K, Ringerud A, Schwabe U, Sermet C, Skiold P, Teixeira I, van Woerkom M, Vitry A, Vončina L, Zara C, Gustafsson L (2012) What lessons can be learned from the launch of generic clopidogrel. Generics and Biosimilars Initiative J 1(2):58–68

    Article  Google Scholar 

  5. Gurbel PA, Tantry US (2007) Clopidogrel resistance? Thromb Res 120:311–321

    Article  CAS  PubMed  Google Scholar 

  6. Wang TH, Bhatt DL, Topol EJ (2006) Aspirin and clopidogrel resistance: an emerging clinical entity. Eur Heart J 27(6):647–654

    Article  PubMed  Google Scholar 

  7. Geisler T, Langer H, Wydymus M, Göhring K, Zürn C, Bigalke B, Stellos K, May AE, Gawaz M (2006) Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur Heart J 27(20):2420–2425

    Article  CAS  PubMed  Google Scholar 

  8. Matetzky S, Shenkman B, Guetta V et al (2004) Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 109:3171–3175

    Article  CAS  PubMed  Google Scholar 

  9. Furman MI, Benoit SE, Barnard MR, Valeri CR, Borbone ML, Becker RC, Hechtman HB, Michelson AD (1998) Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease. J Am Coll Cardiol 31(2):352–358

    Article  CAS  PubMed  Google Scholar 

  10. Momary KM, Dorsch MP, Bates ER (2010) Genetic causes of clopidogrel nonresponsiveness: which ones really count? Pharmacotherapy. 30(3):265–274

    Article  CAS  PubMed  Google Scholar 

  11. Laine M, Arméro S, Peyrol M, Sbragia P, Thuny F, Paganelli F, Bonello L (2013) Clinical impact of genetically determined platelet reactivity. J Cardiovasc Transl Res 6(3):398–403

    Article  PubMed  Google Scholar 

  12. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS (2009) Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 360(4):354–362

    Article  CAS  PubMed  Google Scholar 

  13. Suh JW, Koo BK, Zhang SY, Park KW, Cho JY, Jang IJ, Lee DS, Sohn DW, Lee MM, Kim HS (2006) Increased risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients taking clopidogrel. CMAJ 174(12):1715–1722

    Article  PubMed Central  PubMed  Google Scholar 

  14. Park KW, Kang J, Park JJ, Yang HM, Lee HY, Kang HJ, Koo BK, Oh BH, Park YB, Kim HS (2012) Amlodipine, clopidogrel and CYP3A5 genetic variability: effects on platelet reactivity and clinical outcomes after percutaneous coronary intervention. Heart 98(18):1366–1372

    Article  CAS  PubMed  Google Scholar 

  15. Malinin A, Pokov A, Spergling M, Defranco A, Schwartz K, Schwartz D, Mahmud E, Atar D, Serebruany V (2007) Monitoring platelet inhibition after clopidogrel with the VerifyNow-P2Y12(R) rapid analyzer: the VERIfy Thrombosis risk ASsessment (VERITAS) study. Thromb Res 119(3):277–284

    Article  CAS  PubMed  Google Scholar 

  16. Michelson AD (2009) Methods for the measurement of platelet function. Am J Cardiol 103(3 Suppl):20A–26A

    Article  CAS  PubMed  Google Scholar 

  17. Effect of metoprolol CR/XL in chronic heart failure (1999) Metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet 353(9169):2001–2007

    Article  Google Scholar 

  18. Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, Lubsen J, Lutiger B, Metra M, Remme WJ, Torp-Pedersen C, Scherhag A, Skene A, Carvedilol Or Metoprolol European Trial Investigators (2003) Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol or Metoprolol European Trial (COMET): randomised controlled trial. Lancet 362(9377):7–13

    Article  CAS  PubMed  Google Scholar 

  19. Neubauer H, Krüger JC, Lask S, Endres HG, Pepinghege F, Engelhardt A, Bulut D, Mügge A (2009) Comparing the antiplatelet effect of clopidogrel hydrogensulfate and clopidogrel besylate: a crossover study. Clin Res Cardiol 98(9):533–540

    Article  CAS  PubMed  Google Scholar 

  20. Jeong YH, Koh JS, Kang MK, Ahn YJ, Kim IS, Park Y, Hwang SJ, Kwak CH, Hwang JY (2010) The impact of generic clopidogrel bisulfate on platelet inhibition in patients with coronary artery stents: results of the ACCEL-GENERIC study. Korean J Intern Med 25(2):154–156

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Borsiczky B, Sarszegi Z, Konyi A, Szabados S, Gaszner B (2012) The effect of clopidogrel besylate and clopidogrel hydrogensulfate on platelet aggregation in patients with coronary artery disease: a retrospective study. Thromb Res 129(6):700–703

    Article  CAS  PubMed  Google Scholar 

  22. Tsoumani ME, Kalantzi KI, Dimitriou AA, Ntalas IV, Goudevenos IA, Tselepis AD (2012) Antiplatelet efficacy of long-term treatment with clopidogrel besylate in patients with a history of acute coronary syndrome: comparison with clopidogrel hydrogen sulfate. Angiology 63(7):547–551

    Article  PubMed  Google Scholar 

  23. Tsoumani ME, Kalantzi KI, Dimitriou AA, Ntalas IV, Goudevenos IA, Tselepis AD (2012) Effect of clopidogrel besylate on platelet reactivity in patients with acute coronary syndromes. Comparison with clopidogrel hydrogen sulfate. Expert Opin Pharmacother 13(2):149–158

    Article  CAS  PubMed  Google Scholar 

  24. Arvanitidis K, Ragia G, Iordanidou M, Kyriaki S, Xanthi A, Tavridou A, Manolopoulos VG (2007) Genetic polymorphisms of drug-metabolizing enzymes CYP2D6, CYP2C9, CYP2C19 and CYP3A5 in the Greek population. Fundam Clin Pharmacol 21(4):419–426

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiology Department, University Hospital of Heraklion, P.O. Box 1352, 71110, Heraklion, Crete, Greece

    Michalis Hamilos, Ilias Saloustros, Emmanuel Skalidis, Nikolaos Igoumenidis, Marios Kambouris, Grigorios Chlouverakis, Despina Vougia, Ioannis Loggakis, Panos E. Vardas & George Kochiadakis

Authors
  1. Michalis Hamilos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilias Saloustros
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emmanuel Skalidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nikolaos Igoumenidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marios Kambouris
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Grigorios Chlouverakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Despina Vougia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ioannis Loggakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Panos E. Vardas
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. George Kochiadakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George Kochiadakis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hamilos, M., Saloustros, I., Skalidis, E. et al. Comparison of the antiplatelet effect of clopidogrel hydrogenosulfate and clopidogrel besylate in patients with stable coronary artery disease. J Thromb Thrombolysis 40, 288–293 (2015). https://doi.org/10.1007/s11239-015-1173-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-015-1173-y

Keywords

Search

Navigation