Journal of Thrombosis and Thrombolysis

, Volume 27, Issue 2, pp 154–162

Improving adjunctive treatment in pulmonary embolism and fibrinolytic therapy. The role of enoxaparin and weight-adjusted unfractionated heparin

  • Carlos Jerjes-Sánchez
  • Sergio Villarreal-Umaña
  • Alicia Ramírez-Rivera
  • Anabel Garcia-Sosa
  • Luis Miguel-Canseco
  • Tamara Archondo
  • Esteban Reyes
  • Angel Garza
  • Roberto Arriaga
  • Francisco Castillo
  • Omar Jasso
  • Hector Garcia
  • Martha Bermudez
  • Jose Maria Hernandez
  • Jorge Garcia
  • Pedro Martinez
  • Francisco Rangel
  • Jorge Gutierrez
  • Alfredo Comparan-Nuñez
Article

Abstract

Aim The role of enoxaparin and weight-adjusted unfractionated heparin (UH) as adjunct to fibrinolytic therapy in pulmonary embolism is unknown. Methods In a prospective, open-label, controlled multicenter trial, 80 patients with high-risk pulmonary embolism were enrolled. Forty patients received alteplase infusion plus weight-adjusted UH (24–48 h) and then enoxaparin (7 days). In control group, UH standard regimen was used. There were not differences on pulmonary embolism extension, (P 0.63) and right ventricular hypokinesis (P 0.07) in both groups. In terms of in-hospital survival (P 0.009), escalation treatment (P < 0.001) and in-hospital stay (P < 0.001) study group had better outcome than opposite group. In a 30 (P < 0.001) and 90 (P < 0.001) days follow-up pulmonary perfusion was improved in patients who received enoxaparin versus heparin alone without increasing major bleeding complications. Conclusion Enoxaparin and weight-adjusted intravenous UH as adjunct to 1-h alteplase infusion improve in-hospital and follow-up outcome compared to heparin alone in high-risk PE.

Keywords

Pulmonary embolism Thrombolysis Fibrinolytic therapy Enoxaparin Right ventricular dysfunction 

References

  1. 1.
    Goldhaber SZ, Haire WD, Feldstein ML et al (1993) Alteplase versus heparin in acute pulmonary embolism; randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet 341:507–511PubMedCrossRefGoogle Scholar
  2. 2.
    Sors H, Pacouret G, Azarian R, Meyer G, Charbonnier B, Simmoneau G (1994) Hemodynamic effects of bolus vs. 2-h infusion of alteplase in acute massive pulmonary embolism: a randomized controlled multicenter trial. Chest 106:712–717PubMedCrossRefGoogle Scholar
  3. 3.
    Meneveau N, Schiele F, Metz D et al (1998) Comparative efficacy of a two-hour regimen of streptokinase versus alteplase in acute massive pulmonary embolism: immediate clinical and hemodynamic outcome and one-year follow-up. J Am Coll Cardiol 31:1057–1063PubMedCrossRefGoogle Scholar
  4. 4.
    Jerjes-Sanchez C, Ramirez-Rivera A, Garcia MM et al (1995) Streptokinase and heparin versus heparin alone in massive pulmonary embolism: a randomized controlled trial. J Thromb Thrombolysis 2:227–229PubMedGoogle Scholar
  5. 5.
    Tebbe U, Graf A, Kamke W et al (1999) Hemodynamic effects of double-bolus reteplase versus alteplase infusion in massive pulmonary embolism. Am Heart J 138:39–44PubMedCrossRefGoogle Scholar
  6. 6.
    Jerjes-Sanchez C, Ramirez-Rivera A, Arriaga-Nava R et al (2001) High dose and short-term streptokinase infusion in patients with pulmonary embolism: prospective with seven-year follow-up trial. J Thromb Thrombolysis 12:237–247PubMedCrossRefGoogle Scholar
  7. 7.
    Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W (2002) Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 347:1143–1150PubMedCrossRefGoogle Scholar
  8. 8.
    Konstantinides S, Geibel A, Olschewski M et al (1997) Association between thrombolytic treatment and the prognosis of hemodynamically stable patients with major pulmonary embolism: results of a multicenter registry. Circulation 96:882–888PubMedGoogle Scholar
  9. 9.
    Meneveau N, Seronde MF, Blonde MC et al (2006) Management of unsuccessful thrombolysis in acute massive pulmonary embolism. Chest 129:1043–1050PubMedCrossRefGoogle Scholar
  10. 10.
    Thabut G, Thabut D, Myers RP et al (2002) Thrombolytic therapy of pulmonary embolism. A meta-analysis. J Am Coll Cardiol 40:1660–1667PubMedCrossRefGoogle Scholar
  11. 11.
    Agnelli G, Becattini C, Kischstein T (2002) Thrombolysis vs. heparin in the treatment of pulmonary embolism. A clinical outcome-based meta-analysis. Arch Intern Med 162:2537–2541PubMedCrossRefGoogle Scholar
  12. 12.
    Wan S, Quinlan DJ, Agnelli G, Eikelboom JW (2004) Thrombolysis compared with heparin for the initial treatment of pulmonary embolism. A meta-analysis of the randomized controlled trials. Circulation 110:744–749PubMedCrossRefGoogle Scholar
  13. 13.
    Jerjes-Sanchez C, Elizalde GJ, Sandoval JZ et al (2004) Diagnostico, estratificacion y tratamiento de la tromboembolia pulmonar aguda. Guias y recomendaciones del capitulo de Circulacion Pulmonar de la Sociedad Mexicana de Cardiologia. Arch Cardiol Mex 74(suppl 3):S547–S585Google Scholar
  14. 14.
    Task Force on Pulmonary Embolism, European Society Cardiology (2000) Guidelines on diagnosis and management of acute pulmonary embolism. Eur Heart J 21:1301–1336Google Scholar
  15. 15.
    The Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators (2001) Efficacy and safety of tenecteplase in combination with enoxaparin, abxicimab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet 358:605–613Google Scholar
  16. 16.
    Gulba DC, Tanswell P, Dechend R et al (1997) Sixty-minute alteplase protocol: a new accelerated recombinant tissue-type plasminogen activator regimen for thrombolysis in acute myocardial infarction. J Am Coll Cardiol 30:1611–1617PubMedCrossRefGoogle Scholar
  17. 17.
    Martinez-Sanchez C, Dominguez JL, Aguirre SJ et al (1997) Tratamiento del infarto agudo al miocardio con rt-PA en 60 minutos. Estudio Cooperativo. Arch Inst Cardiol Mex 67:126–131PubMedGoogle Scholar
  18. 18.
    Foussas SG, Zairis MN, Lyras AG et al (2005) Early prognostic usefulness of C-reactive protein added to the thrombolysis in myocardial infarction risk score in acute coronary syndromes. Am J Cardiol 96:533–537PubMedCrossRefGoogle Scholar
  19. 19.
    Cohen M, Demers C, Gurfinkel EP et al (1997) The efficacy and safety of subcutaneous enoxaparin in non-Q-wave coronary events study group. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med 337:447–452PubMedCrossRefGoogle Scholar
  20. 20.
    Goodman SG, Cohen M, Bigonzi F et al, for the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q Wave Coronary Events (ESSENCE) Study Group (2000) Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: one-year results of the essence study. J Am Coll Cardiol 36:693–698Google Scholar
  21. 21.
    (1973) The urokinase pulmonary embolism trial: a national cooperative study. Circulation 47(suppl II):1–108Google Scholar
  22. 22.
    (1974) Urokinase-streptokinase pulmonary embolism trial-phase 2 results. JAMA 229:1606–1613Google Scholar
  23. 23.
    Garcia CA, Jerjes-Sanchez C, Martinez Sanchez C et al (2006) Grupo de Trabajo de la Sociedad Mexicana de Cardiologia y la Asociacion de Cardiologos de Mexico. Guias para el manejo del infarto agudo del miocardio con elevación del segmento ST. Arch Cardiol Mex 76:S3, 1–113Google Scholar
  24. 24.
    Mikkola KM, Patel SR, Parker JA, Grodstein F, Goldhaber SZ (1997) Increasing age is a major risk factor for hemorrhagic complications after pulmonary embolism thrombolysis. Am Heart J 134:69–72PubMedCrossRefGoogle Scholar
  25. 25.
    Meyer G, Gisselbrecht M, Diehl JL, Journois D, Sors H (1998) Incidence and predictors of major hemorrhagic complications from thrombolytic therapy in patients with massive pulmonary embolism. Am J Med 105:472–477PubMedCrossRefGoogle Scholar
  26. 26.
    Jerjes-Sanchez C, Gutierrez-Fajardo P, Ramirez-Rivera A, Treviño H, Villarreal I, Bermudez M (1999) Broadening thrombolytic therapy indications in patients with pulmonary embolism. Chest 116:263SCrossRefGoogle Scholar
  27. 27.
    Hamel E, Pacouret G, Vincentelli D et al (2001) Thrombolysis or heparin therapy in massive pulmonary embolism with ventricular dilatation: results from a 128-patient monocenter registry. Chest 120:120–125PubMedCrossRefGoogle Scholar
  28. 28.
    Meneveau N, Ming LP, Séronde MF et al (2003) In-hospital and long-term outcome after sub-massive and massive pulmonary embolism submitted to thrombolytic therapy. Eur Heart J 24:1447–1454PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Carlos Jerjes-Sánchez
    • 1
  • Sergio Villarreal-Umaña
    • 1
  • Alicia Ramírez-Rivera
    • 1
  • Anabel Garcia-Sosa
    • 1
  • Luis Miguel-Canseco
    • 1
  • Tamara Archondo
    • 1
  • Esteban Reyes
    • 1
  • Angel Garza
    • 1
  • Roberto Arriaga
    • 2
  • Francisco Castillo
    • 1
  • Omar Jasso
    • 1
  • Hector Garcia
    • 1
  • Martha Bermudez
    • 1
  • Jose Maria Hernandez
    • 1
  • Jorge Garcia
    • 1
  • Pedro Martinez
    • 1
  • Francisco Rangel
    • 3
  • Jorge Gutierrez
    • 4
  • Alfredo Comparan-Nuñez
    • 5
  1. 1.Hospital de Enfermedades Cardiovasculares y del Torax, IMSS, MonterreySan Pedro Garza GarciaMexico
  2. 2.Hospital de Cardiología CMN, IMSSMexicoMexico
  3. 3.Hospital PEMEX NorteMexicoMexico
  4. 4.Hospital General de Zona No 33, IMSSMonterreyMexico
  5. 5.Hospital General de Especialidades No. 1, IMSSTijuanaMéxico

Personalised recommendations