New
Strategies
for
Acute
Coronary
Syndromes
Paul
W.
Armstrong
Department
of
Medicine
Faculty
of
Medicine
University
of
Alberta
Edmonton,
Alberta,
Canada
There
have
been
extraordinary
advances
in
our
understanding
of
the
pathophysiology
of
acute
coronary
syndromes
over
the
past
decade.
These
have
provided
new
insights
into
the
pathophysiology
of
atherosclerotic
plaque
rupture,
the
composition
of
intracoronary
thrombus
and,
in
particular,
its
platelet-rich
component
and
the
importance
of
the
coronary
microcirculation
as
it
relates
to
nutrient
left
ventricular
flow.
Simultaneous
with
these
developments
there
has
been
an
appreciation
of
the
heterogeneous
nature
of
patients
presenting
with
an
apparently
similar
clinical
syndrome
yet
manifesting
a
broad
continuum
of
risk
from
death
through
recurrent
myocardial
infarction
to
refractory
ischemia
with
its
attendant
morbidity.
Given
an
increasingly
complex
array
of
therapeutic
choices,
aligning
this
risk
with
the
most
appropriate
and
cost-effective
therapy
is
a
central
future
challenge.
For
patients
without
ST
elevation
acute
coronary
syndromes,
low
molecular
weight
heparin
now
offers
practical
advantages
over
traditional
unfractionated
heparin
and
may
also
result
in
decreased
morbidity.
The
introduction
of
intravenous
platelet
glycoprotein
IIb/IIIa
inhibitors
has
made
a
major
contribution
to
improved
outcomes
in
high
risk
acute
coronary
syndrome
patients
most
especially
those
undergoing
percutaneous
coronary
interventions
and
coronary
artery
bypass
grafting.
For
patients
with
acute
ST
elevation
acute
coronary
syndromes,
accelerated
tPA
remains
the
best
available
fibrinolytic
therapy.
Recently
however
a
new
genetically
engineered
triple
mutation
of
tPA
i.e.
tenecteplase
(TNK)
has
proven
to
be
as
effective
as
tPA
but
less
prone
to
systemic
hemorrhagic
complications.
Because
TNK
can
be
given
as
a
bolus
in
seconds
it
is
well
positioned
to
rekindle
consideration
of
out-of-hospital
fibrinolytic
therapy.
This
may
prove
advantageous
given
the
persisting
delay
from
symptom
onset
to
hospital
presentation
of
such
patients.
An
attractive
new
pharmacologic
strategy
for
such
patients
is
a
half-dose
fibrinolytic
coupled
with
intravenous
IIb/IIIa
platelet
inhibition:
this
appears
to
better
achieve
both
epicardial
and
microcirculatory
flow
and
may
as
well
reduce
the
risk
of
troublesome
reocclusion
and
even
the
potential
for
intracranial
hemorrhage.
Large
Phase
III
trials
are
now
addressing
this
pivotal
issue
will
be
discussed.
The
new
millennium
also
brings
new
opportunities
for
reducing
reperfusion
injury
and
enhancing
myocardial
recovery
and
healing
after
acute
myocardial
infarction.
In
summary,
there
is
an
explosion
of
interest
and
opportunity
to
further
improve
the
care
of
millions
of
patients
world-wide
who
suffer
from
acute
coronary
syndromes.
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