Unstable Angina Treatment References
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Antman EM, Cohen M, Radley D, et al.
Assessment of the treatment effect of enoxaparin for unstable
angina/non-Q-wave myocardial infarction. TIMI 11B-ESSENCE meta-analysis [see
comments]
Circulation 1999; 100 1602-8
BACKGROUND: Two phase III trials of enoxaparin for unstable angina/non- Q-wave
myocardial infarction have shown it to be superior to unfractionated heparin
for preventing a composite of death and cardiac ischemic events. A
prospectively planned meta-analysis was performed to provide a more precise
estimate of the effects of enoxaparin on multiple end points. METHODS AND
RESULTS: Event rates for death, the composite end points of death/nonfatal
myocardial infarction and death/nonfatal myocardial infarction/urgent
revascularization, and major hemorrhage were extracted from the TIMI 11B and
ESSENCE databases. Treatment effects at days 2, 8, 14, and 43 were expressed
as the OR (and 95% CI) for enoxaparin versus unfractionated heparin. All
heterogeneity tests for efficacy end points were negative, which suggests
comparability of the findings in TIMI 11B and ESSENCE. Enoxaparin was
associated with a 20% reduction in death and serious cardiac ischemic events
that appeared within the first few days of treatment, and this benefit was
sustained through 43 days. Enoxaparin's treatment benefit was not associated
with an increase in major hemorrhage during the acute phase of therapy, but
there was an increase in the rate of minor hemorrhage. CONCLUSIONS: The
accumulated evidence, coupled with the simplicity of subcutaneous
administration and elimination of the need for anticoagulation monitoring,
indicates that enoxaparin should be considered as a replacement for
unfractionated heparin as the antithrombin for the acute phase of management
of patients with high-risk unstable angina/non-Q-wave myocardial infarction.

Antman EM, McCabe CH, Gurfinkel EP, et al.
Enoxaparin prevents death and cardiac ischemic events in unstable
angina/non-Q-wave myocardial infarction. Results of the thrombolysis in
myocardial infarction (TIMI) 11B trial [see comments]
Circulation 1999; 100 1593-601
BACKGROUND: Low-molecular-weight heparins are attractive alternatives to
unfractionated heparin (UFH) for management of unstable angina/non-Q- wave
myocardial infarction (UA/NQMI). METHODS AND RESULTS: Patients (n=3910) with
UA/NQMI were randomized to intravenous UFH for >/=3 days followed by
subcutaneous placebo injections or uninterrupted antithrombin therapy with
enoxaparin during both the acute phase (initial 30 mg intravenous bolus
followed by injections of 1.0 mg/kg every 12 hours) and outpatient phase
(injections every 12 hours of 40 mg for patients weighing /=65 kg). The
primary end point (death, myocardial infarction, or urgent revascularization)
occurred by 8 days in 14.5% of patients in the UFH group and 12.4% of patients
in the enoxaparin group (OR 0.83; 95% CI 0.69 to 1.00; P=0. 048) and by 43
days in 19.7% of the UFH group and 17.3% of the enoxaparin group (OR 0.85; 95%
CI 0.72 to 1.00; P=0.048). During the first 72 hours and also throughout the
entire initial hospitalization, there was no difference in the rate of major
hemorrhage in the treatment groups. During the outpatient phase, major
hemorrhage occurred in 1.5% of the group treated with placebo and 2.9% of the
group treated with enoxaparin (P=0.021). CONCLUSIONS: Enoxaparin is superior
to UFH for reducing a composite of death and serious cardiac ischemic events
during the acute management of UA/NQMI patients without causing a significant
increase in the rate of major hemorrhage. No further relative decrease in
events occurred with outpatient enoxaparin treatment, but there was an
increase in the rate of major hemorrhage.


Cohen M
Low molecular weight heparins in the management of unstable angina/non- Q-wave
myocardial infarction
Semin Thromb Hemost 1999; 25 113-21
The safety and efficacy of enoxaparin, dalteparin, and nadroparin have been
studied in five major trials in the treatment of unstable angina/non-Q-wave
myocardial infarction (UA/NQWMI). To date, enoxaparin is the only low
molecular weight heparin (LMWH) to have demonstrated superiority over
unfractionated heparin (UFH) in preventing clinical endpoints in this
indication, including a composite triple endpoint of death, myocardial
infarction, and need for revascularization. Equivalent clinical benefits were
obtained with enoxaparin in two major phase III randomized trials (ESSENCE,
TIMI 11B), and were not accompanied by any increased risk of major hemorrhage.
A meta-analysis of data from TIMI 11B and ESSENCE demonstrated that enoxaparin
was associated with a 20% reduction in death and serious cardiac ischemic
events. The benefit appeared within a few days of starting therapy, was
sustained through 43 days, and has been confirmed to persist one year after
treatment. By contrast, in similar trials, neither dalteparin nor nadroparin
was shown to be superior to UFH in the management of acute coronary syndromes.
The benefit of enoxaparin demonstrated in the ESSENCE study extended across
patient subgroups and was accompanied by substantial cost savings. Differences
in trial design prevent direct comparisons between products, but prescribing
decisions should be based on the available clinical trial evidence.