as measured through the activated partial thromboplas-
tin time (aPTT). Institutions vary considerably regarding
reference values and dose adjustment procedures. Sev-
eral approaches have been used to counteract this limi-
tation, either by more frequent aPTT monitoring or by
adopting a single nomogram for dose adjustment.
Despite such approaches and the availability of state-of-
the-art devices for aPTT measurement, several studies
during the last 5 years have consistently showed that
less than 55% of the population treated with UFH
achieve a specified target aPTT level, usually after at
least 48 hours of therapy.
4
Several studies have shown the clinical efficacy of low-
molecular-weight heparin. Gurfinkel et al
5
published the
first clinical evidence that low-molecular-weight heparin
could be more effective than conventional therapy with
UFH. These findings on safety and efficacy have been
tested and validated with enoxaparin in the Efficacy and
Unfractionated heparin (UFH) has been the treatment
of choice for patients with an acute coronary syndrome
for almost 20 years.
1
Its combination with aspirin repre-
sents a rational therapeutic approach to the thrombotic
process underlying unstable angina (UA) and non-Q-
wave myocardial infarction.
2,3
Yet the use of UFH has a
number of drawbacks, most important of which is the
difficulty in obtaining a target level of anticoagulation,
From the
a
Favaloro Foundation, Buenos Aires, and
b
Brigham and Women’s Hospi-
tal, Boston.
Supported by a research grant from Rhône-Poulenc Rorer (Collegeville, Pa), now
Aventis Pharma.
Submitted February 11, 2000; accepted July 5, 2000.
Reprint requests: Gerardo E. Bozovich, MD, Coronary Unit, Favaloro Foundation,
Av Belgrano 1746, 1093 Buenos Aires, Argentina.
E-mail: bozovich@impsat1.com.ar
Copyright © 2000 by Mosby, Inc.
0002-8703/2000/$12.00 + 0 4/1/109921
doi:10.1067/mhj.2000.109921
Acute Ischemic Heart Disease
Superiority of enoxaparin versus unfractionated
heparin for unstable angina/non-Q-wave
myocardial infarction regardless of activated
partial thromboplastin time
Gerardo E. Bozovich, MD,
a
Enrique P. Gurfinkel, MD, PhD,
b
Elliott M. Antman, MD,
b
Carolyn H. McCabe, BS,
b
and
Branco Mautner, MD,
a
for the TIMI 11B investigators Buenos Aires, Argentina, and Boston, Mass
Background Whether the clinical superiority of enoxaparin versus unfractionated heparin (UFH) depends on a more
stable antithrombotic effect or the proportion of patients not reaching the therapeutic level with UFH has not been
addressed.
Methods All patients participating in the Thrombolysis In Myocardial Infarction 11B trial who received UFH and had
sufficient activated partial thromboplastin time (aPTT) data (n = 1893) were compared with patients who received enoxa-
parin (n = 1938). Patients receiving UFH were divided into 3 categories depending on mean aPTT values throughout 48
hours: subtherapeutic, for those in whom the average aPTT fell below 55 seconds; therapeutic, between 55 and 85 sec-
onds; and supratherapeutic, longer than 85 seconds. Events and bleeding rates were determined at 48 hours.
Results A small portion of patients (6.7%) had a subtherapeutic average aPTT value (n = 127). Forty-seven percent of
patients (n = 891) fell within the therapeutic range, and 46% were in the supratherapeutic level (n = 875). Event rates were
7.0% in the UFH group versus 5.4% with enoxaparin (P = .039). Events rates were higher in every aPTT strata compared
with enoxaparin and statistically significant in the supratherapeutic group (odds ratio 0.65; 95% confidence interval, 0.47-
0.89). Major bleeding rates were 0%, 0.6%, and 0.9% for the subtherapeutic, target, and supratherapeutic strata, respec-
tively, and 0.8% with enoxaparin. Minor hemorrhages occurred in 5.1% of patients receiving enoxaparin versus 3.9%, 2%,
and 2.3%, respectively, for the UFH subgroups (P < .001 for all UFH groups vs enoxaparin).
Conclusions Enoxaparin showed a better clinical profile compared with every level of anticoagulation with UFH.
Potential mechanisms for enoxaparin superiority are stable antithrombotic activity, lack of rebound thrombosis, and intrinsic
superiority. (Am Heart J 2000;140:637-42.)