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European Heart Journal Advance Access originally published online on June 11, 2007
European Heart Journal 2007 28(13):1566-1573; doi:10.1093/eurheartj/ehm179
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Roberto R. Giraldez1,*, José Carlos Nicolau2, Ramon Corbalan3, Enrique P. Gurfinkel4, Ursulo Juarez5, Jose Lopez-Sendon6, Alexander Parkhomenko7, Peter Molhoek8, Satishkumar Mohanavelu1, David A. Morrow1 and Elliott M. Antman1

1 TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 350 Longwood Avenue, 1st Floor, Boston, MA 02115, USA
2 Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil
3 Department of Cardiovascular Diseases, Pontificia Universidad Catolica, Santiago, Chile
4 Fundacion Favaloro, Buenos Aires, Argentina
5 Coronary Care Unit, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico
6 H. Gregorio Maranon, Madrid, Spain
7 Institute of Cardiology, Kiev, Ukraine
8 Enschede, The Netherlands

Received 19 December 2006; revised 7 April 2007; accepted 13 April 2007; online publish-ahead-of-print 11 June 2007.

* Corresponding author. Tel: +1 617 525 6865; fax: +1 888 249 5261; E-mail address: rgiraldez{at}partners.org

Aims: We compared outcomes of ST-elevation myocardial infarction (STEMI) patients randomized to a strategy of either enoxaparin or unfractionated heparin (UFH) to support fibrinolysis.

Methods and results: In the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction Study 25 (ExTRACT-TIMI 25) trial, 20 479 patients undergoing fibrinolysis for STEMI with a fibrin-specific agent (N = 16 283) or streptokinase (SK) (N = 4139) were randomized to enoxaparin throughout their hospitalization or UFH for at least 48 h. The primary end point of death or nonfatal recurrent MI through 30 days occurred in 12.0% of patients in the UFH and 9.8% in the enoxaparin groups when treated with fibrin-specific lytics [odds ratioadjusted (ORadj) 0.78; 95% CI 0.70–0.87; P < 0.001] and 11.8 vs. 10.2%, respectively, when treated with SK (ORadj 0.83; 95% CI 0.66–1.04; P = 0.10; Pinteraction = 0.58). Major bleeding rates including intracranial hemorrhage within the fibrin-specific cohort were 1.2 and 2.0% in the UFH and enoxaparin groups, respectively (P < 0.001) and 2.0% in UFH and 2.4% in enoxaparin patients in the SK cohort (P = 0.16). Interaction tests between antithrombin- and lytic-type were non-significant (P = 0.20). Death, nonfatal MI, or major bleeding was significantly reduced with enoxaparin in the fibrin-specific cohort (ORadj 0.82; 95% CI 0.74–0.91; P < 0.001) and favoured enoxaparin in the SK cohort (ORadj 0.89; 95% CI 0.72–1.10; P = 0.29; Pinteraction = 0.53).

Conclusion: The benefits of an enoxaparin strategy over UFH were observed in both SK and fibrin-specific-treated STEMI patients. Therefore, an enoxaparin strategy is preferred over UFH to support fibrinolysis for STEMI regardless of lytic agent.

Key Words: STEMI • Enoxaparin • Fibrin-specific lytics • Streptokinase


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