Skip to main content
SpringerLink
Log in

ExTRACT-TIMI 25 in perspective: key lessons regarding enoxaparin as an adjunct to fibrinolytic therapy

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

Abstract

Unfractionated heparin (UFH) for 48 h has been the traditional standard anticoagulant with fibrinolytics. The Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction (ExTRACT)-Thrombolysis in Myocardial Infarction (TIMI) 25 trial prospectively studied the usefulness of enoxaparin and found that in patients treated with fibrinolysis, enoxaparin administered throughout the index hospitalization was superior to the standard 48-h UFH infusion. However, enoxaparin increased major bleeding. The data from this large trial were further analyzed across various subgroups and these results support the use of enoxaparin in a broad range of patients. The ExTRACT-TIMI 25 trial employed a novel dosing regimen for enoxaparin adjusted for age and renal function, which was designed to minimize bleeding risk while maintaining the beneficial effects of enoxaparin. Based on the evidence from this trial, the 2007 ST-segment elevation myocardial infarction guidelines now preferentially recommend enoxaparin to be administered throughout the index hospitalization as per the dosing regimen used in ExTRACT-TIMI 25 in most patients treated with fibrinolytic therapy.

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
Fig. 4

Similar content being viewed by others

References

  1. Rosamond W, Flegal K, Friday G et al (2007) Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 115:e69–e171. doi:10.1161/CIRCULATIONAHA.106.179918

    Article  PubMed  Google Scholar 

  2. Antman EM, Hand M, Armstrong PW et al (2008) 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 51:210–247. doi:10.1016/j.jacc.2007.10.001

    Article  PubMed  Google Scholar 

  3. Jollis JG, Mehta RH, Roettig ML et al (2006) Reperfusion of acute myocardial infarction in North Carolina emergency departments (RACE): study design. Am Heart J 152:851.e1–11

    Article  Google Scholar 

  4. Antman EM, Morrow DA, McCabe CH et al (2006) Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med 354:1477–1488. doi:10.1056/NEJMoa060898

    Article  PubMed  CAS  Google Scholar 

  5. Eagle KA, Goodman SG, Avezum A et al (2002) Practice variation and missed opportunities for reperfusion in ST-segment-elevation myocardial infarction: findings from the Global Registry of Acute Coronary Events (GRACE). Lancet 359:373–377. doi:10.1016/S0140-6736(02)07595-5

    Article  PubMed  Google Scholar 

  6. Armstrong PW (2002) Coronary reperfusion: numerators searching for denominators. Lancet 359:371–372. doi:10.1016/S0140-6736(02)07588-8

    Article  PubMed  Google Scholar 

  7. Weaver WD (2003) All hospitals are not equal for treatment of patients with acute myocardial infarction. Circulation 108:1768–1771. doi:10.1161/01.CIR.0000097559.09335.4A

    Article  PubMed  Google Scholar 

  8. Antman EM (2001) The search for replacements for unfractionated heparin. Circulation 103:2310–2314

    PubMed  CAS  Google Scholar 

  9. Antman EM, Morrow DA, McCabe CH et al (2005) Enoxaparin versus unfractionated heparin as antithrombin therapy in patients receiving fibrinolysis for ST-elevation myocardial infarction: design and rationale for the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction study 25 (ExTRACT-TIMI 25). Am Heart J 149:217–226. doi:10.1016/j.ahj.2004.08.038

    Article  PubMed  CAS  Google Scholar 

  10. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41. doi:10.1159/000130554

    Article  PubMed  CAS  Google Scholar 

  11. Levey AS, Bosch JP, Lewis JB et al (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in Renal Disease Study Group. Ann Intern Med 130:461–470

    PubMed  CAS  Google Scholar 

  12. Scirica BM, Morrow DA, Sadowski Z et al (2007) A strategy of using enoxaparin as adjunctive antithrombin therapy reduces death and recurrent myocardial infarction in patients who achieve early ST-segment resolution after fibrinolytic therapy: the ExTRACT-TIMI 25 ECG study. Eur Heart J 28:2070–2076. doi:10.1093/eurheartj/ehm210

    Article  PubMed  CAS  Google Scholar 

  13. Morrow DA, Antman EM, Charlesworth A et al (2000) TIMI risk score for ST-elevation myocardial infarction: a convenient, bedside, clinical score for risk assessment at presentation. Circulation 102:2031–2037

    PubMed  CAS  Google Scholar 

  14. Ruff CT, Wiviott SD, Morrow DA et al (2007) TIMI risk index and the benefit of enoxaparin in patients with ST-elevation myocardial infarction. Am J Med 120:993–998. doi:10.1016/j.amjmed.2007.08.020

    Article  PubMed  CAS  Google Scholar 

  15. Wiviott SD, Morrow DA, Frederick PD et al (2004) Performance of the thrombolysis in myocardial infarction risk index in the National Registry of Myocardial Infarction-3 and -4: a simple index that predicts mortality in ST-segment elevation myocardial infarction. J Am Coll Cardiol 44:783–789

    PubMed  Google Scholar 

  16. Goodman SG, Fitchett D, Armstrong PW et al (2003) Randomized evaluation of the safety and efficacy of enoxaparin versus unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor eptifibatide. Circulation 107:238–244. doi:10.1161/01.CIR.0000050144.67910.13

    Article  PubMed  CAS  Google Scholar 

  17. Gibson CM, Murphy SA, Montalescot G et al (2007) Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-TIMI 25 trial. J Am Coll Cardiol 49:2238–2246. doi:10.1016/j.jacc.2007.01.093

    Article  PubMed  CAS  Google Scholar 

  18. Sabatine MS, Morrow DA, Montalescot G et al (2005) Angiographic and clinical outcomes in patients receiving low-molecular-weight heparin versus unfractionated heparin in ST-elevation myocardial infarction treated with fibrinolytics in the CLARITY-TIMI 28 trial. Circulation 112:3846–3854. doi:10.1161/CIRCULATIONAHA.105.595397

    Article  PubMed  CAS  Google Scholar 

  19. Sabatine MS, Morrow DA, Dalby A et al (2007) Efficacy and safety of enoxaparin versus unfractionated heparin in patients with ST-segment elevation myocardial infarction also treated with clopidogrel. J Am Coll Cardiol 49:2256–2263. doi:10.1016/j.jacc.2007.01.092

    Article  PubMed  CAS  Google Scholar 

  20. Giraldez RR, Nicolau JC, Corbalan R et al (2007) Enoxaparin is superior to unfractionated heparin in patients with ST elevation myocardial infarction undergoing fibrinolysis regardless of the choice of lytic: an ExTRACT-TIMI 25 analysis. Eur Heart J 28:1566–1573. doi:10.1093/eurheartj/ehm179

    Article  PubMed  CAS  Google Scholar 

  21. Mega JL, Morrow DA, Ostör E et al (2007) Outcomes and optimal antithrombotic therapy in women undergoing fibrinolysis for ST-elevation myocardial infarction. Circulation 115:2822–2828. doi:10.1161/CIRCULATIONAHA.106.679548

    Article  PubMed  CAS  Google Scholar 

  22. White HD, Braunwald E, Murphy SA et al (2007) Enoxaparin vs. unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction in elderly and younger patients: results from ExTRACT-TIMI 25. Eur Heart J 28:1066–1071. doi:10.1093/eurheartj/ehm081

    Article  PubMed  CAS  Google Scholar 

  23. Alexander KP, Newby LK, Armstrong PW et al (2007) Acute coronary care in the elderly, part II: ST-segment-elevation myocardial infarction: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology. Circulation 115:2570–2589. doi:10.1161/CIRCULATIONAHA.107.182616

    Article  PubMed  Google Scholar 

  24. White HD, Aylward PE, Huang Z et al (2005) Mortality and morbidity remain high despite captopril and/or Valsartan therapy in elderly patients with left ventricular systolic dysfunction, heart failure, or both after acute myocardial infarction: results from the Valsartan in Acute Myocardial Infarction Trial (VALIANT). Circulation 112:3391–3399. doi:10.1161/CIRCULATIONAHA.105.551143

    Article  PubMed  CAS  Google Scholar 

  25. Fried LF, Shlipak MG, Crump C et al (2003) Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. J Am Coll Cardiol 41:1364–1372. doi:10.1016/S0735-1097(03)00163-3

    Article  PubMed  Google Scholar 

  26. Fox KA, Antman EM, Montalescot G et al (2007) The impact of renal dysfunction on outcomes in the ExTRACT-TIMI 25 trial. J Am Coll Cardiol 49:2249–2255. doi:10.1016/j.jacc.2006.12.049

    Article  PubMed  CAS  Google Scholar 

  27. Grundy SM, Benjamin IJ, Burke GL et al (1999) Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 100:1134–1146

    PubMed  CAS  Google Scholar 

  28. Aguilar D, Solomon SD, Køber L et al (2004) Newly diagnosed and previously known diabetes mellitus and 1-year outcomes of acute myocardial infarction: the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. Circulation 110:1572–1578. doi:10.1161/01.CIR.0000142047.28024.F2

    Article  PubMed  Google Scholar 

  29. Morrow DA, Antman EM, Murphy SA et al (2007) Effect of enoxaparin versus unfractionated heparin in diabetic patients with ST-elevation myocardial infarction in the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction study 25 (ExTRACT-TIMI 25) trial. Am Heart J 154:1078–1084. doi:10.1016/j.ahj.2007.07.027

    Article  PubMed  CAS  Google Scholar 

  30. Murphy SA, Gibson CM, Morrow DA et al (2007) Efficacy and safety of the low-molecular weight heparin enoxaparin compared with unfractionated heparin across the acute coronary syndrome spectrum: a meta-analysis. Eur Heart J 28:2077–2086. doi:10.1093/eurheartj/ehm224

    Article  PubMed  CAS  Google Scholar 

  31. Assessment of the Safety, Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators (2001) Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet 358:605–613

    Article  Google Scholar 

  32. Ross AM, Molhoek P, Lundergan C et al (2001) Randomized comparison of enoxaparin, a low-molecular-weight heparin, with unfractionated heparin adjunctive to recombinant tissue plasminogen activator thrombolysis and aspirin: second trial of Heparin and Aspirin Reperfusion Therapy (HART II). Circulation 104:648–652. doi:10.1161/hc3101.093866

    Article  PubMed  CAS  Google Scholar 

  33. Baird SH, Menown IB, McBride SJ et al (2002) Randomized comparison of enoxaparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction. Eur Heart J 23:627–632. doi:10.1053/euhj.2001.2940

    Article  PubMed  CAS  Google Scholar 

  34. Antman EM, Louwerenburg HW, Baars HF et al (2002) Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction: results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 trial. Circulation 105:1642–1649. doi:10.1161/01.CIR.0000013402.34759.46

    Article  PubMed  CAS  Google Scholar 

  35. Wallentin L, Goldstein P, Armstrong PW et al (2003) Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting: the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS randomized trial in acute myocardial infarction. Circulation 108:135–142. doi:10.1161/01.CIR.0000081659.72985.A8

    Article  PubMed  CAS  Google Scholar 

  36. Kindermann M, Adam O, Werner N et al (2007) Clinical trial updates and hotline sessions presented at the European Society of Cardiology Congress 2007: (FINESSE, CARESS, OASIS 5, PRAGUE-8, OPTIMIST, GRACE, STEEPLE, SCAAR, STRATEGY, DANAMI-2, ExTRACT-TIMI-25, ISAR-REACT 2, ACUITY, ALOFT, 3CPO, PROSPECT, EVEREST, COACH, BENEFiT, MERLIN-TIMI 36, SEARCH-MI, ADVANCE, WENBIT, EUROASPIRE I-III, ARISE, getABI, RIO). Clin Res Cardiol 96:767–786. doi:10.1007/s00392-0591-z

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors received editorial support in the preparation of this manuscript, funded by Sanofi-Aventis, NJ, USA. However, the authors were fully responsible for contents and editorial decisions for this manuscript. Dr. Giugliano had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Giugliano has received honoraria for CME related activity from Sanofi-Aventis and Bristol Myers Squibb and served on the ECG Core Laboratory for the ExTRACT-TIMI 25 Trial, which was supported by a research grant from Sanofi-Aventis. Dr Thomas has no conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Department of Nuclear Cardiology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Deepak Thomas

  2. TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Robert P. Giugliano

Authors
  1. Deepak Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert P. Giugliano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert P. Giugliano.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thomas, D., Giugliano, R.P. ExTRACT-TIMI 25 in perspective: key lessons regarding enoxaparin as an adjunct to fibrinolytic therapy. J Thromb Thrombolysis 27, 1–10 (2009). https://doi.org/10.1007/s11239-008-0284-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-008-0284-0

Keywords

Search

Navigation