Clinical pharmacodynamics and long-term efficacy of Talcom vs. Plavix in patients undergoing coronary stent implantation: a randomized study with 5-year follow-up
Form II clopidogrel bisulfate (Plavix) has been extensively used in patients with acute coronary syndrome. However, the efficacy of form I clopidogrel bisulfate (Talcom) was less investigated. The aim of this study was to investigate the efficacy and safety of Talcom compared with Plavix.
Two hundred and forty-eight patients were recruited after receiving percutaneous coronary intervention (PCI). Participants were randomly assigned to Talcom or Plavix group, and administered with Talcom or Plavix 75 mg od respectively in combination with aspirin 100 mg od for 12 months. Primary endpoints were set as levels of adenosine diphosphate-induced platelet aggregation (PLADP) on the 5th day and at 1 month after randomization. Patients were followed-up for 5 years. Bleeding events and major adverse cardiovascular events (MACE) including cardiac death, non-fatal myocardial infarction, ischemic stroke, target lesion revascularization (TLR), and cardiogenic re-admission were recorded.
On the 5th day and at 1 month after randomization, the antiplatelet effect of Talcom was non-inferior to that of Plavix [PLADP (5th day): 30% (22%, 43%) vs. 33% (22%, 44%), p = 0.007; PLADP (1 month): 29% (19%, 43%) vs. 31% (22%, 43%), p = 0.005]. A total of 208 patients completed the follow-up, the incidences of MACE and bleeding were both comparable, and the MACE-free survival did not differ between the two groups. However, the expenditure was 32% lower for Talcom compared to Plavix during the treatment period.
The antiplatelet effect of Talcom is non-inferior to Plavix, and the clinical efficacy and safety of Talcom and Plavix at 5 years were not significantly different in this study.
KeywordsClopidogrel Plavix Talcom Platelet aggregation Non-inferiority trial
Statement on contributorship and the guarantor
JSL, YSF, TTZ, and JC collected the primary data and undertook the initial data analysis; all authors contributed to the drafting of this manuscript. CJL acts as guarantor.
This study was supported by a grant from the National Natural Foundation of China (Grant No.81170181), a grant from the Jiangsu Province’s Key Provincial Talents Program (ZDRCA2016013), and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD).
Compliance with ethical standards
This research was approved by the Research Ethics Board of the First Affiliated Hospital of Nanjing Medical University.
Conflict of interest
The authors have no conflict of interest to declare.
- 1.Koradia V, Chawla G, Bansal AK (2004) Qualitative and quantitative analysis of clopidogrel bisulphate polymorphs. Acta Pharma 54(3):193–204Google Scholar
- 2.Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Juni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN, Group ESCSD, Guidelines ESCCfP, Societies ESCNC (2017) 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: the task force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 39:213–260. https://doi.org/10.1093/eurheartj/ehx419 CrossRefGoogle Scholar
- 3.Khalili H, Singh R, Wood M, Edwards A, Cooper M, Ayers C, Moss E, Berry JD, Vongpatanasin W, de Lemos JA, Das SR (2016) Premature clopidogrel discontinuation after drug-eluting stent placement in a large urban safety-net hospital. Am J Cardiol 117(4):522–525. https://doi.org/10.1016/j.amjcard.2015.11.037 CrossRefPubMedGoogle Scholar
- 4.Grines CL, Bonow RO, Casey DE, Gardner TJ, Lockhart PB, Moliterno DJ, O’Gara P, Whitlow P (2007) Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents. J Am Dent Assoc 138(5):652–655. https://doi.org/10.14219/jada.archive.2007.0237 CrossRefPubMedGoogle Scholar
- 8.Gurbel PA, Bliden KP, Saucedo JF, Suarez TA, Di Chiara J, Antonino MJ, Mahla E, Singla A, Herzog WR, Bassi AK, Hennebry TA, Gesheff TB, Tantry US (2009) Bivalirudin and clopidogrel with and without eptifibatide for elective stenting: effects on platelet function, thrombelastographic indexes, and their relation to periprocedural infarction results of the CLEAR PLATELETS-2 (Clopidogrel with Eptifibatide to Arrest the Reactivity of Platelets) study. J Am Coll Cardiol 53(8):648–657. https://doi.org/10.1016/j.jacc.2008.10.045 CrossRefPubMedGoogle Scholar
- 9.Steinhubl SR, Kastrati A, Berger PB (2007) Variation in the definitions of bleeding in clinical trials of patients with acute coronary syndromes and undergoing percutaneous coronary interventions and its impact on the apparent safety of antithrombotic drugs. Am Heart J 154(1):3–11. https://doi.org/10.1016/j.ahj.2007.04.009 CrossRefPubMedGoogle Scholar
- 10.Zaid AN, Al Ramahi R, Bustami R, Mousa A, Khasawneh S (2015) Comparative fasting bioavailability of two clopidogrel formulations in healthy Mediterranean volunteers: an in vitro-in vivo correlation. Drug Des Devel Ther 9:2359–2365. https://doi.org/10.2147/DDDT.S78658 CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Ohkubo K, Fujimoto Y, Iwata Y, Kitahara H, Kadohira T, Sugimoto K, Morino T, Kobayashi Y (2014) Efficacy and safety of low-dose clopidogrel in Japanese patients after drug-eluting stent implantation: a randomized pilot trial. Heart Vessel 29(1):1–6. https://doi.org/10.1007/s00380-012-0318-6 CrossRefGoogle Scholar
- 13.Quadros AS, Welter DI, Camozzatto FO, Chaves A, Mehta RH, Gottschall CA, Lopes RD (2011) Identifying patients at risk for premature discontinuation of thienopyridine after coronary stent implantation. Am J Cardiol 107(5):685–689. https://doi.org/10.1016/j.amjcard.2010.10.045 CrossRefPubMedGoogle Scholar
- 14.Biondi-Zoccai GG, Agostoni P, Sangiorgi GM, Airoldi F, Cosgrave J, Chieffo A, Barbagallo R, Tamburino C, Vittori G, Falchetti E, Margheri M, Briguori C, Remigi E, Iakovou I, Colombo A, Real-world Eluting-stent Comparative Italian retrosPective Evaluation Study I (2006) Incidence, predictors, and outcomes of coronary dissections left untreated after drug-eluting stent implantation. Eur Heart J 27(5):540–546. https://doi.org/10.1093/eurheartj/ehi618 CrossRefPubMedGoogle Scholar
- 15.Moreno R, Fernandez C, Hernandez R, Alfonso F, Angiolillo DJ, Sabate M, Escaned J, Banuelos C, Fernandez-Ortiz A, Macaya C (2005) Drug-eluting stent thrombosis: results from a pooled analysis including 10 randomized studies. J Am Coll Cardiol 45(6):954–959. https://doi.org/10.1016/j.jacc.2004.11.065 CrossRefPubMedGoogle Scholar
- 17.Sackett DL, Richardson W, Rosenberg W et al (1997) Evidence-based medicine: how to practice and teach EBM. Churchill Livingstone, New YorkGoogle Scholar