FRONTIERS IN CHF
Frontiers in Congestive Heart Failure
David Tepper, MD
Editor
Randomized Comparison of Enoxaparin
With Unfractionated Heparin for the
Prevention of Venous Thromboembolism
in Medical Patients With Heart Failure or
Severe Respiratory Disease
Abstract. Background. We compared the efficacy and
safety of the low-molecular weight heparin enoxaparin
with unfractionated heparin (UFH) for the prevention
of venous thromboembolic disease in patients with
heart failure or severe respiratory disease.
Methods. This was a multicenter, controlled, ran-
domized, open study in which patients received ei-
ther enoxaparin (40 mg once daily) or UFH (5000
IU three times daily) for 10±2 days in 64 medical
departments in Germany. Patients were stratified
and enrolled according to their underlying disease:
severe respiratory disease or heart failure. The pri-
mary efficacy parameter was a thromboembolic
event up to 1 day after the treatment period.
Results. Of the 665 patients enrolled, 451 pa-
tients were able to be evaluated in the primary effi-
cacy analysis. The incidence of thromboembolic
events was 8.4% with enoxaparin and 10.4% with
UFH. Enoxaparin was at least as effective as UFH,
with a 1-sided equivalence region of –4% (90% con-
fidence interval [CI], –2.5 to 6.5; p=0.015). Enoxa-
parin was associated with fewer deaths, less bleed-
ing, and significantly fewer adverse events (45.8%
vs. 53.8%; p=0.044).
Conclusions. Enoxaparin is at least as effective as
UFH in the prevention of thromboembolic events
in patients with heart failure or severe respiratory
disease. Its beneficial safety profile and once-daily
administration is advantageous for inpatient and
outpatient use.—Kleber FX, Witt C, Vogel G, et al., for
the THE-PRINCE Study Group. Randomized compari-
son of enoxaparin with unfractionated heparin for the
prevention of venous thromboembolism in medical pa-
tients with heart failure or severe respiratory disease.
Am Heart J. 2003;145(4):614–621.
CHF MAY/JUNE 2003 179
Comment. Patients who suffer from decompensated
congestive heart failure are at increased risk of ve-
nous thromboembolic disease for a variety of rea-
sons. The authors of this paper published their data
regarding a multicenter, randomized study, which
involved the use of low-molecular weight heparin in
the form of enoxaparin at a dose of 40 mg once
daily, vs. UFH at a dose of 5000 IU given subcuta-
neously three times daily for a 10-day course. The
trial was conducted in 64 separate medical depart-
ments in Germany. Patients enrolled in the trial
were stratified and enrolled according to the under-
lying pathology, either severe respiratory disease or
heart failure. The end point to determine efficacy
was a thromboembolic event occurring up to 1 day
after the treatment period.
There were 665 patients enrolled in the trial; of
these 451 patients were able to be evaluated using this
end point. The authors found an incidence of 8.4% of
thromboembolic events in those with low-molecular
weight heparin vs. 10.4% in those patients who re-
ceived UFH. Furthermore, there was a lower inci-
dence of death, significant bleeding, and other ad-
verse events noted in the enoxaparin-treated group.
Based on the data from the trial, the authors
concluded that use of enoxaparin, low-molecular
weight heparin, is at least as effective as standard
UFH for thromboembolic prophylaxis in patients
with heart failure or severe respiratory decompen-
sation. The increased safety benefit was also clearly
noted in this regimen. Also of great importance was
the fact that enoxaparin can be administered on a
once-daily regimen, which would therefore enable
its use in outpatient settings as well as inpatient sit-
uations much more readily.
180 FRONTIERS IN CHF
While the initial cost of using low-molecular weight
heparin may be greater, its value to cardiovascular clini-
cians has clearly been demonstrated in this trial. A look
at the pharmacoeconomics of the global picture can
help health care policy makers decide on future uses for
Use of Plasma Brain Natriuretic Peptide
Concentration to Aid in the Diagnosis of
Heart Failure
Abstract. Plasma concentration of brain natriuretic
peptide (BNP), as measured by the Triage BNP
Test, is approved by the Food and Drug Adminis-
tration to aid in the diagnosis of heart failure. This
diagnostic test is available in many institutions. The
purpose of this article is to help the physician know
the appropriate time to order this test and to aid in
interpreting results. To achieve this goal, we review
the physiology of BNP, clinical studies that support
its use for diagnosing heart failure, and confound-
ing variables to consider when BNP is being used
clinically. We show that the BNP test can be ex-
tremely helpful when used in the correct clinical
setting.—Shapiro BP, Chen HH, Burnett JC Jr, et al.
Use of plasma brain natriuretic peptide concentration to
aid in the diagnosis of heart failure. Mayo Clin Proc.
2003;78(4):481–486.
Comment. The subjective complaint of shortness of
breath or dyspnea on exertion is a common com-
plaint in clinical medicine. Since chronic obstruc-
tive pulmonary disease—also known as COPD—
very often is a comorbidity associated with heart
failure patients, it is frequently unclear whether or
not the patient is suffering from decompensated
heart failure, or if the primary ideology of their
symptoms is lung disease. With this in mind, inves-
tigators have previously sought out objective crite-
ria to distinguish between these two entities. Over
the past several years, the use of the natriuretic
peptide family has been given increased attention.
Recently the Food and Drug Administration ap-
proved the use of brain natriuretic peptide (BNP)
CHF MAY/JUNE 2003
this very efficacious and safe intervention in order to
prevent what can otherwise be disastrous outcomes from
thromboembolic venous disease. Further studies in this
regard will likely be forthcoming and assist in clinical
decision making.
for use in the diagnostic workup of heart failure. As
this modality gains increasing popularity it will be
important for clinicians to understand its role in
the diagnosis and management of decompensated
left ventricular systolic dysfunction.
While technology has increased, our ability to use
these resources has to be appropriately addressed.
Not every test or intervention that is available for a po-
tential problem should be utilized. With this in mind,
the idea of “shot-gunning” in approach to the clinical
management of decompensated patients should be
limited to extreme circumstances. By the appropriate
use of the newer biochemical markers we can hope to
tailor therapy appropriately for each individual. In so
doing, we will likely optimize outcomes, reduce costs,
and limit length of stay in hospitalizations for an ever-
increasing number of elderly patients.
This article presents a very timely review of the
Triage BNP (Biosite Inc., San Diego, CA) test. It
will serve as a resource in guiding physicians in the
appropriate use of this test and assisting in the
analysis of the results. It is a comprehensive review
that will help all health care professionals caring for
patients who suffer from respiratory decompensa-
tion. It details the pathophysiology of the disease
entity, and presents important information regard-
ing clinical studies supporting the use of BNP for
patient management.
A robust amount of data exists in this regard,
and the authors of this paper present the informa-
tion in a concise, coherent, and clinically applicable
format. I would advise clinicians to become familiar
with this information.