Supplements Emerging Antithrombotic Therapies: New Developments in Acute Care Medicine
Burden of Disease: Medical and Economic Impact of Acute Coronary Syndromes
Despite advances in treatment, acute coronary syndromes (ACS), which consist mainly of ST-segment elevation myocardial infarction (STEMI) and unstable angina (UA)/non-STEMI (NSTEMI), present an enormous medical, social, and economic burden worldwide. According to public databases, 879 000 patients were discharged from US hospitals with a diagnosis of ACS in 2003. Globally, ACS in the form of myocardial infarction are responsible for almost half of all deaths related to cardiovascular disease. One third of STEMI patients die within 24 hours of onset, and about 15% of UA/NSTEMI patients will die or experience reinfarction within 30 days.
ACS also exact a high toll in terms of treatment-related and indirect economic costs. Direct medical costs of ACS are estimated at $75 billion, with a significant portion going toward drug therapy and associated costs. Data from clinical trials indicate that a management strategy including antithrombotic therapy can reduce ACS-related morbidity and mortality and related costs. More recently developed antithrombotic agents may have clinical and economic advantages over older therapies.
(Am J Manag Care. 2006;12:S430-S434)
Acute coronary syndromes (ACS) are
ischemic cardiovascular pathologies
ranging from unstable angina (UA)
and non-ST-elevation myocardial infarction
(NSTEMI) to classic transmural myocardial
infarction (MI) with ST-segment elevation
(STEMI). In contrast to STEMI, both UA and
NSTEMI are often accompanied by ST-segment
depression, and are closely related to
one another in etiology, clinical course, and
prognosis.1,2 The term UA is used to describe
a variety of symptom complexes that are
more severe and unpredictable than stable
angina but less so than classic MI. UA is
commonly defined as angina pectoris with
symptoms occurring at rest or with minimal
exertion and lasting for at least 10 minutes,
or with severe symptoms occurring either
for the first time or becoming more frequent,
severe, or prolonged than they had previously
been. A diagnosis of NSTEMI is made
when a patient with UA exhibits signs of
myocardial necrosis, as evidenced by the
appearance in serum of troponins or other
biomarkers of cardiac injury but without ST-segment
elevation on the electrocardiograph.2-4 Despite recent advances in their
treatment, both STEMI and NSTEMI, as well
as UA, continue to present an enormous burden
worldwide in terms of their medical,
social, and economic cost.
ACS: Scope of the Problem
ACS are a major source of mortality and
morbidity both during and after hospitalization,1,5 with up to 30% of discharged patients
needing rehospitalization within the first
6 months.6 According to the Centers for
Disease Control and Prevention and the National
Center for Healthcare Statistics,
879 000 patients were discharged in 2003
from hospitals in the United States with a
diagnosis of ACS. Of these, an estimated
497 000 were men and 382 000 were
women. When secondary discharge diagnoses
are included, the number of hospital
discharges was 1 555 000 hospitalizations
for ACS, 946 000 for MI, and 650 000 for UA.
There were 31 000 hospitalizations with
both MI and UA.7 There are variations in
the standards of care among centers and
MI (STEMI and NSTEMI) occurs in
approximately 865 000 persons annually in
the United States, and about one sixth of
these individuals die before being hospitalized.2,7 It is estimated that only about 20% of
these attacks are preceded by long-standing
angina.7 On a global scale, MI is probably
responsible for 40% to 50% of all mortality
related to cardiovascular disease.11 Data
from the Family Heart Study (FHS) of the
National Heart, Lung, and Blood Institute
show that 25% of men and 38% of women
will die within 1 year of having an initial,
recognized MI,7 and mortality (including
sudden death) among patients with UA
ranges from 8% to 13% at 6 months.12,13
According to the FHS, 18% of men and 35%
of women experience a second MI within 6
years after having a recognized first attack.
Within this same interval, heart failure will
disable approximately 22% of men and 46%
of women who have had an MI, and 8% of
men and 11% of women will experience a
Approximately one third of patients with
STEMI (who represent an estimated 30% to
45% of ACS cases7) die within 24 hours of
the onset of ischemia, and many of the survivors
suffer significant morbidity afterward.4 Like STEMI, UA and NSTEMI are
life-threatening, major causes of emergency
medical care and hospitalization.1,2,12 Among
patients with UA or NSTEMI, approximately
15% will die or have a reinfarction within 30
days of diagnosis,3 and about 30% of patients
with UA will have an MI within 3 months.12
In 1996, UA and MI were together responsible
for a reported 1 443 000 hospitalizations
in the United States.1,3 UA is the primary
diagnosis in approximately 800 000 hospitalizations
annually, and a similar number of
episodes probably go unrecognized or are
managed in outpatient settings.14 Early data
from the CRUSADE [Can Rapid Risk
Stratification of Unstable Angina Patients
Suppress Adverse Outcomes with Early Implementation
of the ACC/AHA* Guidelines]
Registry indicate an inhospital mortality
rate of 4.5%, compared with less than 2%
reported in other ACS trials.15
As with many other diseases, the prevalence
of ACS increases with age. Of the more
than 1.4 million persons hospitalized for
ACS in 1996, almost 60% were 65 years of
age or older.1 In the Global Use of Strategies
to Open Occluded Coronary Arteries
(GUSTO) IIb study of coronary vascular
occlusion, the median age for those with
acute STEMI was 63 years, whereas that for
patients with NSTEMI was 66 years.16
Predictions for the year 2020 and beyond
suggest that ischemic heart disease will be
the leading cause of death and disability
worldwide.17 ACS are likely to remain a leading
cause of hospitalization, both as a result
of the aging population and also because of a
growth in risk factors for coronary heart disease
(CHD),1-3 and will continue to present a
major healthcare challenge in the foreseeable
ACS: Economic Burden
ACS exact a high toll in terms of direct,
treatment-related and management costs, as
well as indirect, social and economic costs.18
Among direct US costs in 2006 for CHD,
most of which consist of costs for ACS,
physician and other professional costs are
estimated at $11.1 billion, hospital costs at
$41.8 billion, nursing-home costs at $10.9
billion, the cost of drugs and other medical
durables at $9.8 billion, and home healthcare
at $1.6 billion, for a total of $75.2 billion
(Table).7 Indirect US costs of CHD for
2006 (because of lost productivity) are estimated
to be $142.5 billion (Table).
Clinical studies strongly suggest that a
management strategy based on risk-stratification
of the patient, thrombolytic and anticoagulant
therapy, and when indicated,
early percutaneous coronary intervention
(PCI) and stenting, may reduce ACS-related
morbidity and mortality and their attendant
costs.1,19 Among the means examined for
achieving this goal has been the establishment
of chest pain facilities. These facilities
could be used to distinguish between
patients in whom thoracic pain does or does
not signify a serious risk for acute MI, to
reduce unnecessary hospital admissions and
occupancy of coronary care units,20,21 and to
increase the availability of catheter laboratory
facilities and cardiologists for patients at
greater risk.21 Likewise, studies of the precision
and cost efficacy of diagnosing ACS
have found, for example, that for a 55-year-old
man with nonspecific (atypical) chest
pain, treadmill-exercise echocardiography is
the most cost-effective screening method
(incremental cost-effectiveness ratio [ICER]:
$41 900 per quality-adjusted life-year
[QALY] saved), whereas routine coronary
angiography is more cost-effective than
treadmill-exercise echocardiography for a
man of the same age with typical angina
(ICER: $36 400 per QALY saved).22
The management strategy for ACS calls
for treating evolving acute STEMI, and preventing
the progression of UA and NSTEMI
to acute STEMI and death, by hospitalization
of the patient and the use of antiplatelet
and anticoagulant therapy, either alone or in
conjunction with early revascularization
(either PCI or surgery).1 The current practice
guidelines of the ACC/AHA for patients
with STEMI call for PCI no more than 12
hours (preferably within 90 minutes) after
the onset of symptoms, or for pharmacologic
thrombolytic therapy if PCI is unavailable;
the guidelines recommend coronary artery
bypass graft surgery for suitable patients
who are not candidates for medical thrombolysis
or PCI but who are still in the
early, 6-to 12-hour stages of an evolving
STEMI.4 The 2002 update to the ACC/AHA
guidelines for managing UA/NSTEMI calls for
an early invasive strategy of angiography
and revascularization for patients who have
recurrent angina or ischemia at rest, elevated
levels of cardiac troponins, new ST-segment
depression, or any of several other risk
factors.3 The 2005 ACC/AHA updated guidelines
for PCI also support use of early aggressive
PCI in UA/NSTEMI.23 A conservative
strategy with planned revascularization may
be offered in the absence of these findings.3
One component of the cost of ACS is
pharmacotherapy, which includes antithrombotic
agents such as unfractionated
heparin (UFH) and low molecular weight
Before the introduction of LMWH in the
late 1980s, UFH was the mainstay of
antithrombotic therapy,24-26 and it is still widely
used in the management of ACS.1,4 The
development of LMWH represents a major
step in the quest for alternative antithrombotic
agents to UFH.1
Produced by the degradation of heparin
into shorter polysaccharide chains that contain
the requisite site for binding to
antithrombin to inactivate factor Xa and
thrombin. LMWH do not bind as extensively
to plasma and other proteins as UFH. Hence,
they have greater bioavailability and a more
predictable dose-response effect. This permits
their use by subcutaneous injection
once or twice daily. It also obviates the need
for the regular monitoring of clotting times
that is needed with UFH.13,27,28 Because of
these favorable characteristics, using LMWH
instead of UFH makes it possible to reduce
hospital lengths of stay and their attendant
costs for patients with ACS, by allowing
antithrombotic treatment to continue on an
The predictable effects of LMWH, and the
lack of need for coagulation monitoring with
their use, have led to a significant increase
in their utilization in the management of
ACS.29 But LMWH are considerably more
expensive than UFH, and from a pharmacoeconomic
perspective, this cost differential
partially negates their advantages over
UFH (such as decreased length of hospital
stay). More recently, however, another class
of antithrombotics, factor Xa inhibitors,
have been studied in the setting of ACS.
According to some large, randomized trials,
the introduction of factor Xa inhibitors, such
as fondaparinux, into the acute management
of ACS could lead to clinical advantages as
well as cost savings.30,31
Kenneth Lane and Thomas May contributed to the writing of this article.
Address correspondence to: A. G. G. Turpie, MD, Hamilton Health Sciences-General Hospital, 237 Barton St. E, Hamilton, Ontario, Canada L8L 2X2. E-mail: email@example.com.
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