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Biomarkers of Thrombosis in ST-Segment Elevation Myocardial Infarction: A Substudy of the ATOLL Trial Comparing Enoxaparin Versus Unfractionated Heparin

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Abstract

Background

The aim was to compare the peri-procedural biomarkers of coagulation and platelet activation in patients randomly allocated to intravenous enoxaparin or unfractionated heparin (UFH) in the ATOLL randomized trial (NCT00718471).

Methods and Results

A total of 129 patients (n = 58 enoxaparin and n = 71 UFH) admitted for ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI) were included in this substudy of the ATOLL trial. Activated partial thromboplastin time ratio, anti-Xa activity, von Willebrand factor antigen, prothrombin fragment 1 + 2 (F1 + 2), thrombin–antithrombin complex (TAT), tissue factor pathway inhibitor and soluble CD40 ligand were measured at sheath insertion (T1) and at the end of the PCI (T2) and correlated with 1-month clinical outcomes. Target anticoagulation levels at T2 were more readily achieved in patients receiving enoxaparin compared to those receiving UFH (80.3 vs 18.2%, p < 0.0001). Increased levels of F1 + 2 and TAT measured at T2 were associated with the incidence of the composite ischemic endpoint (p = 0.04 and p = 0.03) and all-cause mortality (p < 0.0001 and p = 0.002). Release of F1 + 2 between T1 and T2 also predicted the composite ischemic endpoint (312 ± 513 vs 37 ± 292, p = 0.04) and net clinical outcome (185 ± 405 vs 3.2 ± 278, p = 0.03).

Conclusions

During primary PCI, enoxaparin achieved therapeutic levels more frequently than UFH. Higher level of thrombin generation measured at the end of the PCI procedure was associated with more frequent ischemic events.

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Acknowledgements

We would like to thank Nicolas Vignolles, Benjamin Bertin, Anzaha Ghalia, Karine Brochard, and Sissel Paulsrud for their technical assistance. Link to the webpage of the department http://pitiesalpetriere.aphp.fr/departement-de-cardiologie.

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Authors and Affiliations

  1. Sorbonne Université-Univ Paris 06 (UPMC), ACTION Study Group, INSERM, UMRS 1166, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), 47-83 bld de l’Hôpital, 75013, Paris, France

    Johanne Silvain, Stephen A. O’Connor, Mathieu Kerneis, Marie Hauguel-Moreau, Michel Zeitouni, Pavel Overtchouk, Delphine Brugier, Sophie Galier, Jean-Philippe Collet & Gilles Montalescot

  2. Emergency and Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China

    Yan Yan

  3. Service d’Hématologie Biologique, Pitié-Salpêtrière Hospital (AP-HP), Université Paris 6, Paris, France

    Annick Ankri

  4. Methodology and Statistical Unit, Centre Hospitalier Universitaire Lariboisière (ACTION Group, AP-HP, Université Paris 7), Paris, France

    Eric Vicaut & Patrick Ecollan

  5. Service mobile d’urgence et de reanimation (SMUR), Pitié-Salpêtrière Hospital (AP-HP), Université Paris 6, Paris, France

    Johanne Silvain, Stephen A. O’Connor, Yan Yan, Mathieu Kerneis, Marie Hauguel-Moreau, Michel Zeitouni, Pavel Overtchouk, Annick Ankri, Delphine Brugier, Eric Vicaut, Patrick Ecollan, Sophie Galier, Jean-Philippe Collet & Gilles Montalescot

Authors
  1. Johanne Silvain
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  2. Stephen A. O’Connor
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  3. Yan Yan
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  4. Mathieu Kerneis
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  5. Marie Hauguel-Moreau
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  6. Michel Zeitouni
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  7. Pavel Overtchouk
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  8. Annick Ankri
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  9. Delphine Brugier
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  10. Eric Vicaut
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  11. Patrick Ecollan
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  12. Sophie Galier
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  13. Jean-Philippe Collet
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  14. Gilles Montalescot
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Consortia

for the ATOLL Investigators

  • G. Montalescot
  • , U. Zeymer
  • , J. Silvain
  • , B. Boulanger
  • , M. Cohen
  • , P. Goldstein
  • , P. Ecollan
  • , X. Combes
  • , K. Huber
  • , C. Pollack Jr
  • , J. F. Bénezet
  • , O. Stibbe
  • , E. Filippi
  • , E. Teiger
  • , G. Cayla
  • , S. Elhadad
  • , F. Adnet
  • , T. Chouihed
  • , S. Gallula
  • , A. Greffet
  • , M. Aout
  • , J. P. Collet
  •  & E. Vicaut

Corresponding author

Correspondence to Gilles Montalescot.

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Funding

This study was supported by Sanofi-Aventis and ACTION Study Group, www.action-coeur.org.

Conflict of interest

J Silvain has received research grants, honorarium or travel support from Actelion, Amed, Amgen, Algorythm, Astra-Zeneca, Bayer, Daiichi-Sankyo, Eli Lilly, Fondation de France, Gilead Science, Iroko Cardio, Sanofi-Aventis and Saint-Jude Medical; M. Kerneis has received research grants from Sanofi, Fédération Française de Cardiologie, and Société Française de Cardiologie, and lectures and consulting fees from ESC, AstraZeneca, Daiichi-Sankyo, and Bayer; E. Vicaut has received research grants from Boehringer, Pfizer, Sanofi, LFB, Abbott, Fresenius, Medtronic, Hexacath, CERC, Novartis, and Elli Lilly; J.P. Collet has received research grants or honorarium from AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eli-Lilly, Fédération Française de Cardiologie, Lead-Up, Medtronic, MSD, Sanofi-Aventis, and WebMD; G. Montalescot has received research grants or honorarium from ADIR, Amgen, AstraZeneca, Bayer, Berlin Chimie AG, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, Cardiovascular Research Foundation, Celladon, CME Resources, Daiichi-Sankyo, Eli-Lilly, Europa, Elsevier, Fédération Française de Cardiologie, Fondazione Anna Maria Sechi per il Cuore, Gilead, ICAN, Janssen, Lead-Up, Menarini, Medtronic, MSD, Pfizer, Sanofi-Aventis, Servier, The Medicines Company, TIMI Study Group, and WebMD; S.A. O’Connor, Yan Yan, M. Hauguel-Moreau, M. Zeitouni, P. Overtchouk, A. Ankri, D. Brugier, P. Ecollan, and S. Gallier declare no potential conflicts of interest that might be relevant to this work.

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Silvain, J., O’Connor, S.A., Yan, Y. et al. Biomarkers of Thrombosis in ST-Segment Elevation Myocardial Infarction: A Substudy of the ATOLL Trial Comparing Enoxaparin Versus Unfractionated Heparin. Am J Cardiovasc Drugs 18, 503–511 (2018). https://doi.org/10.1007/s40256-018-0294-z

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