The Safety and Efficacy of Subcutaneous Enoxaparin
Versus Intravenous Unfractionated Heparin and
Tirofiban Versus Placebo in the Treatment of
Acute ST-Segment Elevation Myocardial
Infarction Patients Ineligible for Reperfusion (TETAMI)
A Randomized Trial
Marc Cohen, MD, FACC,
* Gian Franco Gensini, MD,† Frans Maritz, MD,‡
Enrique P. Gurfinkel, MD, P
H
D, FACC,
§ Kurt Huber, MD, FACC, Ari Timerman, MD, P
H
D,¶
Maria Krzeminska-Pakula, MD,
# Nicolas Danchin, MD, FACC,** Harvey D. White, DS
C
,††
Jose Santopinto, MD, FACC,
‡‡ Frederique Bigonzi, MD,§§ Carole Hecquet, MS,§§ Luc Vittori, MS,§§
on behalf of the TETAMI Investigators
Newark, New Jersey; Florence, Italy; Bellville, South Africa; Buenos Aires, Argentina; Vienna, Austria; Sa˜o Paulo,
Brazil; Lodz, Poland; Paris, France; Auckland, New Zealand; and Bahia Blanca, Argentina
OBJECTIVES The aims of the Safety and Efficacy of Subcutaneous Enoxaparin Versus Intravenous
Unfractionated Heparin and Tirofiban Versus Placebo in the Treatment of Acute ST-
Segment Elevation Myocardial Infarction Patients Ineligible for Reperfusion (TETAMI)
study were to demonstrate that enoxaparin was superior to unfractionated heparin (UFH) and
that tirofiban was better than placebo in patients with acute ST-segment elevation myocardial
infarction (STEMI) who do not receive timely reperfusion.
BACKGROUND An optimal treatment strategy has not been identified for the many STEMI patients
ineligible for acute reperfusion.
METHODS A total of 1,224 patients were enrolled in 91 centers in 14 countries between July 1999 and
July 2002. Patients with STEMI ineligible for reperfusion were randomized to enoxaparin,
enoxaparin plus tirofiban, UFH, or UFH plus tirofiban. All patients received oral aspirin. The
primary efficacy end point was the 30-day combined incidence of death, reinfarction, or recurrent
angina; the primary analysis was the comparison of the pooled enoxaparin and UFH groups.
RESULTS The incidence of the primary efficacy end point was 15.7% enoxaparin versus 17.3% for UFH
(odds ratio 0.89 [95% confidence interval {CI} ϭ 0.66 to 1.21]) and 16.6% for tirofiban versus
16.4% for placebo (odds ratio 1.02 [95% CI 0.75 to 1.38]). The Thrombolysis In Myocardial
Infarction (TIMI) major hemorrhage rate was 1.5% for enoxaparin versus 1.3% for UFH
(odds ratio 1.16 [95% CI 0.44 to 3.02]) and 1.8% versus 1% for tirofiban versus placebo (odds
ratio 1.82 [95% CI 0.67 to 4.95]).
CONCLUSIONS This study did not show that enoxaparin significantly reduced the 30-day incidence of death,
reinfarction, and recurrent angina compared with UFH in non-reperfused STEMI patients.
However, enoxaparin appears to have a similar safety and efficacy profile to UFH and may be
an alternative treatment. Additional therapy with tirofiban did not appear beneficial. (J Am
Coll Cardiol 2003;42:1348 –56) © 2003 by the American College of Cardiology Foundation
Approximately 750,000 people in the U.S. suffer an acute
myocardial infarction (MI) each year (1). For patients
presenting within 12 h of symptom onset, the standard of
care is prompt coronary reperfusion with either thrombol-
ysis or percutaneous coronary intervention (PCI) (2,3).
However, the majority still does not receive reperfusion-
therapy (4), owing to presentation later than 12 h after
See page 1357
symptom onset or to other clinical or circumstantial factors
(5,6). While extending the time window for reperfusion
sounds promising (7–10), to date, prospective randomized
trials have been unable to substantiate a benefit for such a
course of action. There remains, therefore, no consensus on
how to treat non-reperfused ST-segment elevation MI
(STEMI) patients who normally constitute a high-risk
group, with minimum 13% mortality at 30 days (11).
Antithrombotic therapy may be an alternative to late
reperfusion therapy, by enhancing endogenous thrombolysis
From the *Newark Beth Israel Medical Center, Newark, New Jersey; †University
of Florence, Florence, Italy; ‡Karl Bremer Hospital, Bellville, South Africa; §Favaloro
Foundation, Buenos Aires, Argentina; University Clinic for Internal Medicine,
Vienna, Austria; ¶Dante Pazzanese Institute of Cardiology, Sa˜o Paulo, Brazil;
#Medical University Lodz, Lodz, Poland; **Georges Pompidou Hospital, Paris,
France; ††Green Lane Hospital, Auckland, New Zealand; ‡‡Leonidas Lucero
Municipal Hospital, Bahia Blanca, Argentina; and §§Aventis Pharmaceuticals, Paris,
France. Supported by an educational grant from Aventis Pharma. Aventis Pharma
supported the design, conduct and reporting of this study, in consultation with the
Steering Committee.
Manuscript received March 12, 2003; revised manuscript received April 28, 2003,
accepted May 9, 2003.
Journal of the American College of Cardiology Vol. 42, No. 8, 2003
© 2003 by the American College of Cardiology Foundation ISSN 0735-1097/03/$30.00
Published by Elsevier Inc. doi:10.1016/S0735-1097(03)01040-4