Chapter 2 Unstable Angina/Non-ST-Elevation Myocardial Infarctionfor anticoagulant agents (Table 2.4). ESC down-
grades evidence for unfractionated heparin to IB
(older studies), upgrades evidence for fondaparinux
for a conservative approach (to IA), based on the
single large and blinded OASIS-5 study [15], but
limits its recommendations with an invasive
approach because of catheter thrombosis risk (not
recommended with an urgent invasive approach;
give with heparin for a non-urgent invasive
approach). ESC also downgrades enoxaparin (to
IIaB), given the superior safety of fondaparinux in
OASIS-5 [15]. Bivalirudin also receives a IB recom-
mendation by ESC for an invasive approach but
for a different reason: the key supporting study,
ACUITY, although large, was unblinded [16]. ESC
more explicitly endorses GP IIb/IIIa therapy in
patients at intermediate to high risk in addition to
oral antiplatelet agents (e.g., clopidogrel and aspirin),
especially with elevated troponins, ST-segment
depression, or diabetes [20]. ESC, as ACC/AHA,
generally favors an invasive approach for high risk
patients, but adds diabetes, renal insuffi ciency, and
intermediate risk (in addition to high risk) more
explicitly to indications favoring invasive evalua-
tion, which may occur within 72 hours (versus 24–
48 in the ACC/AHA guidelines).
Future directions
Whereas the incidence and risk of STEMI have
decreased over the past 25 years, the relative fre-
quency of UA/NSTEMI has increased. The early risk
of UA/NSTEMI has decreased with application of
evidence-based management [21], but risk remains
relatively high long-term (i.e., comparable to
STEMI). Hence, improving long-term UA/NSTEMI
outcomes remains a challenge for the future.
Improving prehospital and ED assessment should
aim at more effi cient entry into the healthcare
system, diagnosis and risk stratifi cation (e.g., using
biomarker changes still in the normal range but
rising and with the aid of non-traditional biomark-
ers) and earlier initiation of therapy. The future
likely will witness increased use of new imaging tests
such as multislice coronary CT angiography, espe-
cially if radiation risks are further reduced, and
cardiac MRI to assess chest pain patients with pos-
sible ACS [2]. The concept of a network of “heart
attack centers” has been proposed to improve MI
care in the future, with evidence favoring interven-
tions at experienced centers and at earlier time inter-
vals [22]. However, the preferred strategy (initial
invasive vs. initial conservative) and timing of inva-
sive evaluation for subsets of patients with UA/
NSTEMI continues to be debated and is an appro-
priate topic for ongoing (e.g., TIMACS) and future
research studies. In contrast to evidence of benefi t
of invasive strategies for high-risk patients, growing
evidence suggests that an initial conservative
approach is preferred for patients at low risk of UA/
NSTEMI, particularly low-risk women [7–9].
Antiplatelet therapy continues to evolve, with
higher dose clopidogrel and new thienopyridines
(e.g., prasugrel [23]) being tested, including short
acting, intravenously administered agents [24]. The
future may include greater application of platelet
function analyzers to titrate therapeutic dosing to
individual patient needs. Anticoagulant choices have
proliferated (e.g., with the addition of fondaparinux
[15] and bivalirudin [16] to unfractionated and low
molecular weight heparins), and continued evolu-
tion in their application in UA/NSTEMI can be
expected with the goal of maximum benefi t at lowest
bleeding risk. Greater emphasis and application is
needed in adjusting dose for renal function, older
age, and female sex with these increasingly potent
antithrombotic regimens to preserve safety and
improve overall clinical benefi t [17]. Testing of
more biocompatible stents, less prone to thrombosis
and restenosis, also can be expected, including bio-
degradable stents [25].
Greater and more effective application of second-
ary prevention including cardiac rehabilitation
should benefi t UA/NSTEMI and all CHD patients in
the future [18], guided by trials of lifestyle, pharma-
ceutical, and surgical interventions. Finally, more
effective primary prevention strategies, including
better identifi cation of the “ACS-prone” individual
are anticipated, including life-time risk assessment
and selected application of imaging tests (e.g., with
coronary calcium scans or carotid intima-media
thickness assessment) to detect preclinical disease
[26,27]. Predictive medicine thus is an impor-
tant feature on the future horizon of UA/NSTEMI
and the full spectrum of atherothrombotic disease.References available online at http://www.Wiley.com/go/
AHAGuidelineHandbook.