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

Am J Cardiovasc Drugs. 2018 Dec;18(6):503-511. doi: 10.1007/s40256-018-0294-z.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Antithrombin III
  • Biomarkers
  • CD40 Ligand / blood
  • Enoxaparin / administration & dosage
  • Enoxaparin / adverse effects
  • Enoxaparin / therapeutic use*
  • Factor Xa / analysis
  • Female
  • Heparin / administration & dosage
  • Heparin / adverse effects
  • Heparin / therapeutic use*
  • Humans
  • Lipoproteins / analysis
  • Male
  • Middle Aged
  • Partial Thromboplastin Time
  • Peptide Hydrolases / blood
  • Percutaneous Coronary Intervention / methods*
  • Prothrombin / analysis
  • ST Elevation Myocardial Infarction / blood*
  • ST Elevation Myocardial Infarction / mortality
  • ST Elevation Myocardial Infarction / surgery*
  • von Willebrand Factor / analysis

Substances

  • Anticoagulants
  • Biomarkers
  • Enoxaparin
  • Lipoproteins
  • Von Willebrand antigen
  • antithrombin III-protease complex
  • lipoprotein-associated coagulation inhibitor
  • von Willebrand Factor
  • CD40 Ligand
  • Antithrombin III
  • Prothrombin
  • Heparin
  • Peptide Hydrolases
  • Factor Xa

Associated data

  • ClinicalTrials.gov/NCT00718471