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 Abstract
Acute ST-segment elevation myocardial
infarction occurs due to coronary plaque
rupture and subsequent formation of an
occlusive thrombus. Patients
survival depends largely on rapid and
sustained restoration of antegrade blood
flow in the infarct-related coronary
artery. The concept of coronary
reperfusion has evolved over the course of
the past 20 years on two fronts :
thrombolysis and primary percutaneous
coronary intervention. The standard
thrombolytic agent, the front-loaded
recombinant tissue plasminogen activator,
is superior to streptokinase in achieving
a higher rate of coronary reperfusion and
improving patient survival. Newer
thrombolytic agents currently available
can be administered as single intravenous
bolus dose rather than continuous
infusion. Primary coronary
angioplasty by balloon dilation, and stent
implantation in the setting of acute ST
elevation MI is associated with better
short- and long-term outcome compared with
thrombolysis, but is only available in 5%
of hospitals worldwide. Many
clinical studies have evaluated the
benefit of strategies that combine the use
of antiplatelet glycoprotein IIB/IIIa
inhibitors with angioplasty or
thrombolysis, or that combine
half-dose thrombolysis with angioplasty.
Transferring patients with acute ST
elevation MI from hospitals than do not
have angioplasty facility to others that
have such facility offers a better
outcome over on-site thrombolysis.
Aspirin, beta blockers, ACE inhibitors,
and statins should be included in the
standard care regardless of the
reperfusion strategy these patients
receive.
Introduction
Acute ST-segment elevation myocardial
infarction (AMI) is, in most instances,
due to coronary atherosclerotic plaque
rupture culminating in thrombus formation
and total occlusion of an epicardial
coronary artery. Such plaque rupture
can be spontaneous or precipitated by
intense physical or emotional stress(1,2).
A major determinant of prognosis in
patients with AMI is a prompt and
sustained restoration of brisk blood flow
in the infarct-related coronary artery
which can be achieved by intravenous
thrombolytic agent, or by performing
primary percutaneous coronary intervention
(PPCI), i.e., percutaneous transluminal
coronary angioplasty (PTCA) by balloon
dilation, or stent implantation. Efficacy
and safety of newer single-bolus
thrombolytic agents, and combinations of
antiplatelet agents, such as glycoprotein
IIb/IIIa inhibitors, with PPCI have been
evaluated in several clinical trials(3).
Thrombolysis
in AMI
Since the use of streptokinase (SK) more
than 16 years ago(4),
newer thrombolytic agents have been
developed that aim at improving coronary
reperfusion, left ventricular salvage, and
patient survival by molecular structure
mutations of recombinant tissue
plasminogen activator (rt-PA,
alteplase) thus modifying fibrin affinity,
hepatic clearance, plasma half-life, and
the ease of drug administration.
Although SK
is the most widely used thrombolytic
agent, front-loaded rt-PA is considered as
the gold standard agent and results in a
higher rate of coronary repercussion and
lower 30-day mortality compared with AK(5).
rt-PA is definitely the thrombolytic drug
of choice for extensive or anterior wall
MI, and high-risk patients. AK, on the
other hand, is reserved for patients with
non-complicated
acute inferior wall MI, and for
low-risk patients.
Thrombolytics offer the best results when
administered early after the onset of
chest pain, and as soon as possible when
the patient presents to the emergency
department (ED), with door-to-needle time
(i.e., time from the presentation to ED to
the initiation of thrombolysis ) of <
60 minutes.
New rt-PA mutants, including
tenecteplase (TNK), lantoplase, and
reteplase, are administered as single or
double-bolus intravenous injections.
The former two agents were found to be as
effective as rt-PA, however lantoplase,
but not TNK, was associated with higher
incidence of intercranial hemorrhage(6).
Post-thrombosis
patients are referred to coronary
angiography when they develop recurrent
angina, heart failure, life-threatening
arrhythmia, or in the presence of
significant myocardial ischemic burden on
pre-discharge symptom-limited exercise
stress testing (with or without
radionuclide cardiac imaging). In
the real world, however, this
ischemia-driven policy is not practiced
widely, and cardiologists tend to perform
coronary angiography more liberally, since
up to 36% of patients who receive
thrombolysis undergo angioplasty prior to
discharge(7).
A more liberal use of coronary angiography
post-AMI allows early diagnosis of
patients with left main or multi-vessel
coronary artery disease who will benefit
from coronary bypass surgery.
Coronary angiography will also identify
patients with a significantly diseased
infarct-related artery who might have
false-negative stress testing(9).
Primary Percutaneous Coronary
Intervention (PPCI)
Thrombolysis
has several drawbacks, including failure to
restore coronary flow with persistence of
chest pain and ST elevation, reclusion,
occurrence of side effects especially
intercranial bleeding, and inability to give
the medication in the presence of a
contraindication.
PPCI
implies transferring the patient from the ED
to the catheterization laboratory, without
administering thrombolysis, with the
intention of performing coronary angiogram,
and in suitable candidates, balloon dilation
or stenting.
Several
clinical trials have clearly shown that PPCI
is superior to thrombolytic therapy in the
setting of acute ST elevation MI(9,10-12).
Initial trials comparing primary balloon
angioplasty with thrombolytics revealed
superior short-and long-term mortality
benefit, with a mortality reduction
of
32%(13),
as well as less incidence of recurrent
ischemia, reinfection, and stroke. Moreover,
the length of stay and the total cost are in
favor of primary balloon angioplasty over
thrombolysis.
Coronary
stenting in the setting of AMI, once thought
to be unsafe due to the presence of
intraluminal thrombus, was proven by many
clinical studies to be superior to balloon
angioplasty (14-19).
Patients undergoing primary balloon
angioplasty experience coronary reocclusion
in 10-15% of the cases, higher than that
among patients who undergo the procedure on
elective basis. Moreover, up to 50% will have restenosis, and 20% will need repeat revascularization(20,21).
Stenting, to a large extent, reduces these
limitations and achieves a more brisk
coronary flow, reduced in-hospital recurrent
ischemia and abrupt closure, and, on the
long term, less target vessel
revascularization and major adverse cardiac
events. Recently, drug-eluting stents
(DES) have been introduced
into the coronary interventional
arena. These stents release local
pharmacological cytostatic or cytotoxic
drug, such as sirolimus or paclitaxel to the
arterial wall thus suppressing neointimal
growth and reducing the incidence of
in-stent restenosis. Although initial
studies enrolled only non-acute MI patients
with de novo coronary lesions, it is
expected that in the coming few years there
will be a broader use of DES in more complex
lesions and patients, including acute MI(22).
Despite
logistic limitations of systematic PPCI in
all AMI patients, including the availability
of catheterization laboratory around the
clock, socioeconomic and financial factors,
it is considered by some authorities to be
the routine standard coronary reperfusion
strategy(23).
The
advantage of PPCI is achieved when performed
by experienced operators in a timely fashion
(door-to-balloon time, i.e., time from
patient's
presentation to balloon inflation, of <
90 minutes). Current guidelines indicate
that PPCI is recommended as an alternative
to thrombolysis if performed in a timely
fashion by skilled individuals who perform
>75 procedures/year in a high-volume
center (>200 procedures/year) with
surgical back-up(24),
hence, high-volume hospitals have better
outcome and lower mortality with PPCI
compared with low-volume community hospitals(25).
Although the issue of routine
stress testing or coronary angiography post-PCI
is still controversial, stress testing is
only indicated for patients who develop
post-PCI angina, especially within the first
6-9 months after the procedure, and
probably for high-risk patients, such as
those who had anterior wall MI and stent
implantation in the proximal left anterior
descending coronary artery. Otherwise,
there is no survival advantage of performing
routine stress testing for all post-PCI
patients(8,9).
Smoking cessation should be
stressed upon despite a low rate of quitting
smoking after coronary events(26).
Aggressive medical therapy in revascularized
patients should also include aspirin, beta
blockers, ACE inhibitors, and statins.
Glycoprotein
(GP) IIb/IIIa inhibitors
These
agents inhibit the platelet GP IIb/IIIa
receptors that bind fibrinogen, and thus
disaggregate platelets and cause
dissolution of platelet-rich thrombus.
They were initially used during high-risk
coronary interventions to reduce the
incidence of acute coronary occlusion due
to thrombus formation and dissection(27).
Recently, these agents (especially
abciximab) have been used in combination
with thrombolysis or PPCI to facilitate
mechanical intervention, reduce the
epicardial thrombus burden and improve
distal reperfusion, with the intention of
improving myocardial salvage and patient's
outcome(28,29).
23 GUSTO-V study found that
half-dose reteplase plus abciximab showed
no mortality benefit over full dose
reteplase alone despite lower incidence of
recurrent ischemia and reinfarction, as
well as the need for coronary intervention
in the combination arm(30).
Using
GP IIb/IIIa inhibitors with PPCI was
evaluated in the CADILLAC study (23)
where 4 arms were compared : primary PTCA
with or without abciximab, and stent with
or without abciximab. As expected,
outcome with stent was superior to PTCA
regardless of the use of abciximab.
Stent plus abciximab was associated with
lowest 30-day mortality ever reported in
AMI reperfusion therapy (2%). The
primary end-point (combined incidence of
death, reinfarction, target vessel
revascularization, and stroke) at 6 months
was less in the stent arms compared with
PTCA arms (10.2% vs 11.5% respectively)
whether abciximab was used or not.
In
addition to facilitating angioplasty with
GP IIb/IIIa inhibitors, using half-dose
thrombolytic agent prior to PCI might
potentially offer advantage over PPCI
alone. The PACT study(31),
however, addressed this issue and failed
to show a mortality benefit despite a
better left ventricular function and
reduction of the need for urgent
revascularization in the facilitated
strategy arm.
The
superiority of PPCI over thrombolysis
prompted the initiation of several
clinical trials to evaluate the safety,
feasibility and outcome of transporting
AMI patients from hospital without PPCI
facility to others with this capability
rather than administering thrombolysis at
the hospital the patient presents to (32).
In these studies, SK(33)
and rt-PA(34,35)
were compared with transfer for PPCI.
The combined end-point of death,
reinfarction, and stroke was
reduced by 65% and 40% at 30 days
(33,34)
respectively, and by 39% at 6 weeks(35).
Overall, these studies suggest that
transferring patients for PPCI is
recommended when this can be done with a
clean and quick manner(32).
Table 1 shows the 30-day mortality rate
associated with different reperfusion
strategies.
Table 1 :
Thirty-day
mortality among patients with acute ST
elevation MI
according to the strategy of coronary
reperfusion
Local
and global perspective
Several
hospital in the area have efficient PPCI
capabilities but published data of their
experience are scarce. A study of
PPCI in Jordan(35)
evaluated the short- and long-term
outcomes of 74 patients with acute
ST-elevation MI who were prospectively
followed-up for a mean duration of 20
months (range 6-30). The mean age of
the group was 54 years (range 32-78) and
91% were men. Smoking, diabetes, and
hypertension were present in 65%, 28% and
20% respectively.
Anterior
wall MI was diagnosed in 64% of the whole
group and 65% of the smokers. All had
coronary angiography. The infarct-related
artery was totally occluded in 78%, and
subtotally occluded in 16%. The remaining
6% had non-obstructive disease.
Subsequently, 58 patients
(78.4%) had PPCI including balloon
angioplasty for 13.8% and stenting for
86.2% with a door-to-balloon time of 58.5
minutes (range 20-90). Six patients
(8.1%) underwent bypass surgery and the
rest (13.5%) received medical therapy
because they had non-obstructive or
diffuse coronary lesions, or because they
refused surgery.
A
brisk coronary flow in the infarct-related
artery was achieved in 91% of the PPCI
group, similar to results from
other studies that achieved brisk
flow in 90-96% of cases. In-hospital
complications included 2 deaths (2.7%),
one major stroke, and one case of acute
occlusion post-stent necessitating
emergency CABG on day 2. There was
no major bleeding or groin hematomas. The
length of stay, which was remarkably short
(82% of PPCI patients stayed <5 days),
was consistent with data from larger
studies. During the follow-up period of
the PPCI group, the 30-days mortality was
3.4%, and the 1 year mortality was 5.2%.
On
a global level, less than half of AMI
patients eligible for thrombolytic therapy
receive these agents. Moreover,
door-to-needle time falls within the
recommended 60-minute limit in 50% of
cases. Only 50% of hospitals
worldwide, and 20% of American hospital
have cardiac catheterization facility
capable of performing PPCI with variable
frequency in the West that ranges from
0.3% in some regions in England to 12% in
California(37)
and one third of high risk patients
achieve the recommended door-to-balloon
time of < 60 +
30 minutes(38).
Conclusions
Rapid
restoration of blood flow in the occluded
epicardial coronary artery in patients
with acute ST-segment elevation myocardial
infarction improves left ventricular
function and overall survival. PPCI is the
best reperfusion
strategy when performed in a timely
fashion by experienced operators,
especially with the use of stents and GP
IIb/IIIa inhibitors(39).
If a patient presents to a facility
without cardiac catheterization facility,
a clean and rapid transfer to another
facility for PPCI is safe and offers
survival advantage over on-site
thrombolysis. If thrombolysis is the
chosen strategy, front-loaded rt-PA is the
standard regimen, and streptokinase can be
used in low-risk patients. Newer
thrombolytic agents, such as tenecteplase,
which are as effective as rt-PA can be
administered as a single bolus
intravenous injection.
The
choice of reperfusion strategy should take
into consideration the level of local
expertise, available resources, cost, and
other socioeconomic factors.
Aspirin, beta blockers, ACE inhibitors,
and statins should be used in these
patients, unless there is a
contraindication. Life style
changes, including smoking cessation,
healthy diet and regular exercise should
also be encouraged.
References
Other Topics:
Review
Article # 1
- Clearing the
Cervical Spine in the Acutely
Injured
Review
Article # 2
- Imaging Findings
in Severe Acute Respiratory Syndrome (SARS)
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