World Journal of Cardiovascular Diseases, 2013, 3, 551-560 WJCD Published Online December 2013 (
Acute ST-segment myocardial infarction—Evolution of
treatment strategies
Dennis T. L. Wong1,2, Rishi Puri1,3, Peter J. Psaltis1,2, Stephen G. Worthley1,3, Matthew I. Worthley1,3
1Department of Medicine, University of Adelaide, Adelaide, Australia
2MonashHeart, Monash Medical Centre, Clayton, Australia
3Cardiovascular Research Centre, Royal Adelaide Hospital, Adelaide, Australia
Received 29 October 2013; revised 28 November 2013; accepted 6 December 2013
Copyright © 2013 Dennis T. L. Wong et al. This is an open access article distributed under the Creative Commons Attribution Li-
cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In
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The commonest cause of acute myocardial infarction
involves the rupture or erosion of vulnerable athero-
sclerotic plaques followed by aggregation of platelets
and subsequent thrombus formation, leading to par-
tial or complete epicardial coronary arterial occlusion.
Over the last 25 years, advancement in therapeutic
options for acute myocardial infarction has resulted
in substantial improvement in morbidity and mortal-
ity. As a result, the absolute risk reduction of in-hos-
pital deaths for patients presenting with STEMI has
been on the decline in the last decade. The focus of
the treatment for acute myocardial infarction invol-
ves achieving epicardial and microvascular patency,
prevention of recurrent ischaemic events while bal-
ancing the risk of bleeding. This involves antiplatelet
and antithrombotic therapies or fibrinolytic agents
when timely performance of primary percutaneous
coronary intervention is not possible. We review the
evolution of treatment strategies for STEMI that has
contributed to the improvement in patient outcome.
Keywords: Myocardial Infarction; STEMI; PCI;
Coronary Artery Intervention
Pathophysiology of Acute Myocardial Infarction
The commonest cause of acute myocardial infarction in-
volves the rupture or erosion of vulnerable atheroscle-
rotic plaques followed by aggregation of platelets and
subsequent thrombus formation, leading to partial or
complete epicardial coronary arterial occlusion [1,2]. Mi-
crocirculatory perfusion is compromised by this throm-
botic process due to reduced coronary artery blood flow
through fixed epicardial stenoses, as well as distal em-
bolisation of thrombus. During the early phase of coro-
nary occlusion, the discrepancy between myocardial oxy-
gen supply and demand results in myocardial ischaemia.
If ischaemia persists, myocardial injury becomes irre-
versible, resulting in myocardial necrosis. This typically
extends from the subendocardium towards the subepi-
cardium. Reimer and Jennings [3] first described the
concept of “wavefront phenomenon of myocardial death”.
The major determinant of final infarct size, transmural
necrosis and microvascular damage is the duration of
ischaemia. Previous studies have validated the associa-
tion between increased duration of ischaemia with worse
myocardial perfusion and increased mortality rate in pa-
tients treated with fibrinolysis [4] and primary percuta-
neous coronary intervention (primary-PCI) [5]. Therefore,
the cornerstone for management of ST-segment elevation
myocardial infarction (STEMI) involves:
1) Rapid restoration of epicardial and microvascular
blood flow utilising combination of pharmacological and
percutaneous intervention;
2) Prevention of recurrent ischaemic events with anti-
thrombotic and antip latelet therapies;
3) Reducing effect of myocardial necrosis;
4) Reducing in-hospital and out-of-hospital complica-
5) Preventing future events.
Over the last 25 years, therapeutic options for treat-
ment of patients wi t h my ocar dial i nfarction have improved
substantially. As a result, the absolute risk reduction of
in-hospital deaths for patients presenting with STEMI
has been on the decline in the last decade [6]. We review
the evolution of treatment strategies for STEMI that has
contributed to the improvement in patien t outcome.
D. T. L. Wong et al. / World Journal of Cardiovascular Diseases 3 (2013) 551-560
The main goal is prompt reperfusion of myocardial blood
flow which has been shown to reduce mortality [7]. The
options include pharmacological reperfusion with fibri-
nolytic agents and primary-PCI. In major centres with
primary-PCI capability, primary-PCI has become the
standard of care. However, fibrinolysis remains the most
viable treatment option in patients presenting to non-PCI
capable hospitals whose transport time to a PCI-capable
hospital is greater than 120 min utes [8].
2.1. Fibrinolysis
A major breakthrough leading to considerable improve-
ment in survival after STEMI was heralded by the intro-
duction of fibrin o lysis in th e 1990’s as a pharmacological
reperfusion therapy [9]. The development of fibrinolytic
agents has undergone an evolution from non-fibrin spe-
cific agents (streptokinase and urokinase) administered
via intravenous infusion, to infusions of fibrin-specific
agents (tissue plasminogen activator [tPA]), to bolus only
fibrin specific agents (rPA, TNK-tPA). The evolution of
these fibrinolytic therapies was associated with incre-
mental benefits to outcome. In the seminal GUSTO trial,
tPA was first shown to have a mortality advantage over
streptokinase [10]. Subsequently, reperfusion with TNK-
tPA was associated with greater vessel patency than
streptokinase, along with less systemic bleeding but
similar mortality benefit as tPA [11]. An important ad-
vantage conferred by TNK-tPA has been the ease of bo-
lus administration, however, its use has not translated to
further reductions in 30-day or late mortality compared
to earlier generation fibrinolytics [11]. Nonetheless, its
simpler dosage regimen does allow for wider application
outside of hospital, more timely administration and fewer
treatment errors. Studies have shown that the earlier ad-
ministration of fibrinolysis is associated with greater
benefit in preservation of left ventricular ejection fraction
and reduction in mortality [12-14 ].
2.2. Failed Fibrinolysis
Up to 40% of patients treated with fibrinolysis fail to
achieve restored microvascular flow to the infarct terri-
tory. This is defined by the persistence of chest pain and
less than 50% reduction in ST-segment elevation at 90
mins after fibrinolysis. The factors associated with failed
pharmacological reperfusion include delay to presenta-
tion and treatment, infarct location and concomitant the-
rapies [15]. In the case of failed thrombolytic reperfusion,
a strong body of evidence supports the role of emergent
angiography and rescue PCI rather than re-administration
of fibrinolytics [16]. Rescue PCI was shown by Gersh-
lick et al. to be associated with lower rates of death, re-
infarction, severe heart failure and stroke 6 months after
STEMI compared to conservative therapy and repeated
thrombolysis. The rate of event free survival at 6 months
among patients treated with rescues PCI was 84.6%, as
compared with 70.1% among those receiving conserva-
tive therapy and 68.7% among those undergoing repeated
thrombolysis (overall P = 0.004) [16]. Subsequently, a
meta-analysis showed that rescue PCI was associated
with improved clinical outcomes for STEMI patients
after failed fibrinolytic therapy but the benefits is associ-
ated with increased risk of stroke and minor bleeding
compared to conservative strategy [17]. Other studies
such as the ASSENT-4 PCI (Assessment of the Safety
and Efficacy of a New Treatment Strategy with Percuta-
neous Coronary Intervention) have assessed the role of
routine emergency PCI after fibrinolysis, (also known as
“facilitated PCI”) and found that this approach is associ-
ated with an increase in the composite of death, heart
failure and shock compared to primary-PCI alone (18.6%
vs. 13.4%, P = 0.005) [18]. Similarly, the use of facili-
tated PCI after administration of half dose r-PA and ab-
ciximab (glycoprotein IIb/IIIa inhibitor) was also found
not to improve outcome compared to primary PCI with
administration of abciximab in the cath lab in the FI-
NESSE (Facilitated Intervention for Enhanced Reperfu-
sion Speed to Stop Events) trial [19].
2.3. Primary Percutaneous Coronary
Despite the clear benefits of fibrinolytic therapy com-
pared with no reperfusion and its ease of use, there were
still issues of both efficacy and safety that limits its use.
These issues include:
1) Normalisation of blood flow (as assessed by TIMI
flow grade 3) occurs in only 50% - 60% of patients
treated with fibrinolysis [10,20]. The clinical benefits of
fibrinolytic therapy correlate only with restoration of
TIMI grade 3 flow.
2) High incidence (20% - 30%) of early recurrence of
ischaemia with 5% - 15% [20,21] of frank fibrinolytic
coronary reocclusion and reinfarction in 3% - 5% [22,23]
despite initial apparent successful fibrinolysis.
3) bMajor haemorrhagic complications occurring in
2% - 3% of patients with the most serious being in-
tracerebral haemorrhage which occurs in as many as 1%
4) There is a high proportion (20% - 30%) of patients
particularly older adults who are not candidates for fi-
brinolytic therapy because of contraindications such as
active internal bleeding, a recent stroke or hypertension
In the early 1990s, it was hypothesised that these prob-
lems could be overcome by the use of primary-PCI. Al-
though the implementation of primary-PCI requires more
resources and is more difficult to quickly implement than
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D. T. L. Wong et al. / World Journal of Cardiovascular Diseases 3 (2013) 551-560 553
fibrinolysis studies have shown that when both methods
of reperfusion are available, primary-PCI offer better
clinical outcomes than fibrinolysis. In a meta-analysis
that reviewed 23 randomised trials consisting of 7739
patients, primary-PCI resulted in lower rates of stroke
(1% vs. 2%, P = 0.004), early death (7% vs. 9%, P =
0.0002) and non-fatal reinfarction (3% vs. 7%, P < 0.001)
compared to fibrinolysis [14]. Nonetheless, these bene-
fits of primary-PCI remain firmly dependent on timely
implementation. Traditionally, this has been measured by
“door-to-balloon time”, which represents the interval
between presentation of the patient to hospital and the
achievement of coronary artery patency by balloon an-
gioplasty. Studies have demonstrated that the incremental
gains from primary PCI are lost when door-to-balloon
time and door-to-needle time (time from hospital arrival
to initiation of fibrinolytic therapy) are greater than 60
min and 114 min respectively [17,26,27]. Notably, rela-
tive 1 year mortality rates increase by 7.5% for every 30
minute delay in reperfusion [28]. Therefore efficient and
effective clinical systems that are able to deliver timely
and consistent reperfusion are required to preserve the
advantage of primary-PCI over fibrinolysis. As reducing
door-to-balloon time is crucial, strategies involving the
performance of 12-lead ECG triage and emergency de-
partment activation of primary-PCI have been proposed.
A study including 349 patients showed that such a-
straegy reduced th e median door-to-balloon time fro m 98
minutes to 56 minutes, compared to conventional strat-
egy [29]. The key to achieving a balance between trans-
fer for primary-PCI and fibrinolysis in hospitals without
invasive services remains a challenge. Current guidelin es
recommend transfer for primary-PCI if the door-to-bal-
loon time is expected to be less than 90 minutes. When
this criterion can be satisfied, the DANAMI-2 study
showed that transfer for primary-PCI results in lower
rates of recurrent myocardial infarction, unplanned re-
vascularisation and stroke compared to onsite fibrinoly-
sis. However a reduction in mortality was not demon-
strated [30 ].
2.4. In-Lab Strategies during Primary
Percutaneous Coronary Intervention
2.4.1. Antithrombotic Therapies
In order to optimally restore myocardial perfusion during
primary-PCI, effective antithrombotic therapies are re-
quired.Unfractionated heparin (UFH) remains the most
common antithrombotic therapy used with an initial in-
travenous bolus of 70 IU/kg during primary-PCI. Recent
studies have shown that low molecular weight heparin
(LMWH) is better than UFH during primary-PCI. An
open label ATOLL trial randomly assigned 901 STEMI
patients to enoxaparin (intravenous bolus of 0.5 mg/kg)
or UFH (initial intravenou s bolus of 70 - 100 IU withou t
or 50 - 70 IU with glycoprotein IIb/IIIa inhibitor) before
primary-PCI [31]. There was no significant reduction in
the rate of primary outcome of death, complication of MI,
procedure failure or major bleeding with enoxaparin
(28% vs. 34%; relative risk 0.83, 95% CI 0.68 - 1.01).
The secondary end-point of death, recurrent MI or acute
coronary syndrome, or urgent revascularisation however
occurred significantly less often with enoxaparin (7% vs.
11%; relative risk 0.59, 95% CI 0.38 - 0.91). Further-
more two meta-analyses have concluded that the use of
LMWH (generally enoxaparin) compared to UFH leads
to lower rates of mortality and major bleeding [32,33].
More recently bivalirudin, a short acting direct throm-
bin inhibitor, has emerged as alternative and possibly
more efficacious antithrombotic therapy during primary-
PCI. The HORIZONS AMI trial enrolled 3600 STEMI
patients and randomised patients to either bivalirudin
(initial bolus of 0.75 mg/kg followed by an intravenous
infusion of 1.75 mg/kg per hour that was discontinued
after PCI) plus provisional glycoprotein IIb/IIIa inhibitor
or to UFH plus planned GP IIb/IIIa prior to primary-PCI.
Patients treated with bivalirudin had reduced major
bleeding (8.3% vs. 4.9%, P < 0.001). The 30 day car diac
mortality and total mortality were also reduced in the
patients treated with bivalirudin (2.1% vs. 3.1%, P =
0.047) [34].
2.4.2. Parenteral Antiplatelet Therapies
Abciximab, a chimeric monoclonal antibody fragment
targeting the glycoprotein IIb/IIIa receptor, prevents
platelet aggregation by blocking the binding of the GP
IIb/IIIa receptor to fibrinogen, thereby inhibiting fi-
brinogen-platelet bridging. It has been shown to be asso-
ciated with a reduction in the composite endpoints of
death, recurrent myocardial infarction and urgent revas-
cularisation in patients undergoing primary-PCI [35-37].
However in the CADILLAC trial, the clinical benefit of
abciximab in stented patients was not confirmed. It was
observed that there was no difference in the rate of rein-
farction or in left ventricular function at six months [38].
In a meta-analysis, abciximab therapy was associated
with significant reductions in mortality at 30 days (2.4%
vs. 3.4%, P = 0.047 with placebo) and six to twelve
months (4.4% vs. 6.2%, P = 0.01) and in reinfarction at
30 days (1.0% vs. 1.9%, P = 0.03); in addition there was
no increase in bleeding. This analysis provides support
for the concept that abciximab is beneficial in reducing
acute ischemic events during primary PCI with stenting
[39]. The intracoronary delivery of abciximab however
has not been proven to be superior to intravenous ad-
ministration in two recent randomised controlled trials
[40,41]. Small molecule glycoprotein IIb/IIIa inhibitors
(tirofiban and eptifibatide) have not been extensively
studied but mechanistic studies have also suggested im-
Copyright © 2013 SciRes. OPEN ACCESS
D. T. L. Wong et al. / World Journal of Cardiovascular Diseases 3 (2013) 551-560
proved vessel patency [4 2, 4 3 ] .
2.4.3. Stents
In patients treated with primary-PCI for STEMI, de-
ployment of stents is now routine. The benefit of drug
eluting stent (DES) platforms over bare metal stents
(BMS) has been examined. In a meta-analysis that in-
cluded thirteen clinical trials with 7244 STEMI patients,
treatment with DES was associated with decreased target
vessel revascularisation and myocardial infarction rates
[44]. Furthermore, there was no increase in cardiac death
or stent thrombosis occurrence with DES [44].
2.4.4. Aspiration Th rombect omy
Another recent development during primary-PCI is aspi-
ration thrombectomy. Thrombus removal using aspira-
tion thrombectomy devices (e.g. EXPORT catheter) has
been recognised as a strategy that is associated with bet-
ter epicardial and myocardial perfusion. This can be ex-
plained by less distal embolisation of thrombus ordinar-
ily resulting in microvascular damage. This was first
shown by the TAPAS study which randomised 1071 pa-
tients to conventional PCI vs. manual thrombus aspira-
tion. Patients treated with thrombus aspiration had lower
rates of myocardial blush grade 0 or 1 (17.1 vs. 26.3%, P
< 0.001) [45]. In addition to myocardial perfusion meas-
ures, a meta-analysis including nine randomised trials
with 2417 patients also showed that adjunctive aspira-
tion thrombectomy during primary-PCI is associated
with a significant reduction in 30-day mortality [46].
2.4.5. Re ducing Bl e ed ing Compl ications
Patients treated with primary-PCI for STEMI are at in-
creased risk of bleeding complications because they are
concurrently managed with multiple antithrombotic and
antiplatelet therapies. Bleeding complications have been
linked with increased morbidity and mortality [47,48].
Studies have shown that reduction in bleeding complica-
tions may lead to improved longer term clinical out-
comes, including mortality [49,50]. A number of phar-
macologic and procedural strategies can be employed to
reduce the risk of bleeding associated with primary-PCI.
The two main strategies that have been associated with
reduction in bleeding complications and mortality are
bivalirudin and radial artery access. Bivalirudin, a direct
thrombin inhibitor, as previously discussed was shown in
the HORIZONS AMI study to have reduced major
bleeding and mortality in STEMI patients treated with
2.4.6. Radial versus Femoral Artery Access
Important advances have been made in elective PCI with
respect to reduced access site bleeding [51] and ultima-
tely post-procedure mortality [52,53 ], through the advent
of radial artery puncture compared to the traditional
femoral artery approach. The RIFLE-STEACS (Radial
Versus Femoral Randomised Investigation in ST-Eleva-
tion Acute Coronary Syndrome) and RIVAL (A Trial of
Trans-radial Versus Trans-Femoral Percutaneous Coro-
nary Intervention (PCI) Access Site App roach in Patients
With Unstable Angina or Myocardial Infarction Managed
With an Invasive Strategy) studies explored the hypothe-
sis that the safety associated with radial artery access
may also translate into mortality benefit in STEMI pa-
tients. In the latter study, Mehta and colleagues com-
pared the efficacy and bleeding outcomes in patients with
STEMI (n = 1958) and non STEMI (n = 5063) separately
in those randomised to radial versus femoral arterial ac-
cess. They found that radial artery access reduced the
primary outcome (death/myocardial infarction/stroke/
non-coronary artery bypass graft related major bleeding)
compared with femoral access in all-comers (3.1% vs.
5.2%; hazard ratio [HR]:0.6; P = 0.026) while also re-
ducing the rates of all-cause mortality at 30 days (1.3%
vs. 3.2%; HR 0.39, P = 0.006) and the composite of
death, myocardial infarction and stroke (2.7% vs. 4.6%;
HR 0.59; P = 0.031) [54]. Interestingly, this effect on
mortality outcome was specific for STEMI patients
treated with primary PCI (1.4% radial vs. 3.1% femoral;
HR: 0.46), as it did not apply to patients in the non-
STEMI cohort (3.8% vs. 3.5%, P = 0.49), death/myo-
cardial infarction / stroke (3.4% vs. 2.7%, P = 0.176) or
all-cause mortality (1.3% vs. 0.8%, P = 0.082) [54].
Similar results were corroborated in the RIFLE-STEACS
study, in which 1001 patients were randomised to radial
(n = 500) and femoral (n = 501) approach at 4-high vol-
ume centres between January 2009 and July 2011. The
primary endpoint was the 30-day rate of net adverse
clinical events (NACEs) defined as composite of cardiac
death, stroke, myocardial infarction, target lesion revas-
cularisation and bleeding. Radial access in patients with
STEMI was associated with lower 30-day NACEs com-
pared to femoral access (13.6% vs. 21%). In addition,
radial access was also associated with significantly lower
rates of cardiac mortality (5.2% vs. 9.2%), bleeding
(7.8% vs. 12.2%, P = 0.026) and shorter hospital stay (P
= 0.03) [55]. The results of these two studies highlight
the safety, efficacy and benefit of radial arterial access
during primary-PCI and herald its use as the preferred
option in patients with STEMI, for interventional cardi-
ologists who have adequate experience and expertise in
radial approach.
2.5. Oral Pharmacotherapies
The evolution of our focus in modern treatment of
STEMI to invasive management is fundamentally en-
abled by the developments in antiplatelet and antithrom-
botic therapies. Our improved understanding that plate-
Copyright © 2013 SciRes. OPEN ACCESS
D. T. L. Wong et al. / World Journal of Cardiovascular Diseases 3 (2013) 551-560 555
lets play a central role in the development of STEMI has
led to the use of more effective antiplatelet therapies
which has been shown to be improve clinical outcomes.
The greatest clinical challenge for the use of these phar-
macotherapies is finding the balance between avoiding
bleeding events and effective suppression of ischaemic
2.6. Oral Antiplatelet Therapies
Aspirin has been the mainstay treatment for all patients
undergoing either pharmacological or primary-PCI.
Therefore, all patients with acute coronary syndromes
and without contraindications should receive aspirin 150
- 300 mg [56].
The second class of antiplatelet therapy is thienopyri-
dine antagonist of ADP. It has been shown that patients
younger than 75 years treated with fibrinolysis random-
ised to receive clopidogrel (300 mg loading dose and 75
mg daily compared with placebo) achieved improved
rates of vessel patency 3 - 5 days later with a non-sig-
nificant reduction in recurrent myocardial infarction
(2.5% vs. 3.6%, P = 0.08) [57]. In addition, among
45,852 patients treated for myocardial infarction, there
was a 7% reduction in hospital mortality following the
addition of clopidogrel (75mg a day added to aspirin,
without loading dose) compared to placebo [58]. The
issue of clopidogrel loading dose was recently evaluated
in the CURRENT-OASIS 7 trial which assigned 25,086
patients with ACS (29.2% STEMI) to either clopidogrel
600 mg loading dose on day 1 followed by 150 mg daily
for 6 days and 75 mg thereafter or clopidogrel 300 mg
loading dose followed by 75 mg daily [59]. The rate of
primary outcome (cardiovascular death, MI, or stroke at
30 days) was not statistically different (4.2% vs. 4.4%, P
= 0.3) between the two groups. Major bleeding occurred
significantly more often in patients who received higher
clopidogrel dose (2.5% vs. 2%, P = 0.01 in the overall
population and 1.6% vs. 1.1%, P = 0.009 in the PCI sub-
group). However, the higher dose of clopidogrel was
associated with a significant reduction in the secondary
outcome of definite stent thrombosis among patients who
underwent PCI (0.7% vs. 1.3%, P = 0.0001).
Prasugrel which irreversibly inhibits the P2Y12 recep-
tor at the same site as clopidogrel was recently compared
to clopidogrel in the TRITON-TIMI 38 trial of 13,608
moderate to high risk ACS patients undergoing PCI, in-
cluding 3534 STEMI patients [60]. In patients with
STEMI at 15 month follow up, the primary efficacy
endpoint of card iovascular death, non fatal MI o r nonfatal
stroke occurred significantly less often in patients treated
with prasug rel (9.9% vs. 12.4%; HR 0 .81; 95% CI 0.73 -
0.9, P < 0.001), driven primarily by a significant reduc-
tion in nonfatal AMI (7.4% vs. 9.7%, P < 0.001). In addi-
tion, the rate of definite or probable stent thrombosis was
also significantly reduced in the prasugrel group (1.6%
vs. 2.8%, P < 0.001). However, a subset of patients had
increased risk of bleeding, specifically those >75 years
old, those <60 kg in weight and those with a history of
prior stroke.
Another antiplatelet agent, ticagrelor which b locks the
P2Y12 receptor reversibly, has a more rapid onset of ac-
tion than clopidogrel. Its efficacy in the treatment of
STEMI has recently been studied in the PLATO trial. At
12 months, the composite primary endpoint (death from
vascular causes, MI, or stroke) occurred significantly less
often in patients receiving ticagrelor (9.8% vs. 11.7%
with clopidogrel, HR 0.84, 95% CI 0.77 - 0.92, P <
0.001). Th ere w as no sign if icant d ifferen ce in the r ates of
major bleeding between the two groups (11.6% and 11.2%,
respectively; P = 0.43), but ticagrelor was associated
with a significantly increased risk of major bleeding not
related to CABG (4.5% vs. 3.8%, P = 0.03). In addition,
the secondary endpoints of the rates of myocardial in-
farction (5.8% vs. 6.9%, P = 0.005), death from vascular
causes (4.0% vs. 5.1%, P = 0.001), and death from any
cause (4.5% vs. 5.9%; P < 0.001) were all significantly
lower in the ticagrelor group [61].
Taken together, there is compelling evidence for the
use of dual therapy with aspirin and complementary an-
tiplatelet agents. The relevant data apply both to the
overall management of patients with STEMI and fur-
thermore to the primary PCI setting. Although recent
results indicate that prasugrel and ticagrelor may have an
advantage over clopidogrel, individual patient criteria
relating to the risk of bleeding must be taken into con-
sideration before selecting a regime. Furthermore, the
cost and availability of newer agents would also be a
In summary, the combination of antiplatelet and anti-
thrombotic therapies needs to strike a balance between
optimising ischaemic outcomes, while reducing bleeding
1) In general, all patients should receive dual anti-
platelet agents (aspirin and Clopidogrel, Prasugrel or
Ticagrelol) and one antithrombin agent (unfractionated
heparin, enoxaparin, bivalirudin or fondaparinux, but not
a combination).
2) In patients with increased risk of bleeding and inva-
sive strategy is planned, use of bivalirudin is supported
by strong data [34].
3) In patients with increased risk of bleeding and con-
servative management is planned, fondaprinux is associ-
ated with reduced bleeding and mortality [62].
There is evidence to support the additive benefits of
combination antiplatelet agents (aspirin, thienopyridines,
and glycoprotein IIb/IIIa inhibition).
4) For patients with elevated troponin levels undergo-
ing PCI, abciximab in add ition to clopidogrel and asp irin
Copyright © 2013 SciRes. OPEN ACCESS
D. T. L. Wong et al. / World Journal of Cardiovascular Diseases 3 (2013) 551-560
further reduces ischaemic events [63]. This should be
commenced in the catheterisation laboratory rather than
soon after admission as this has been shown to reduce
major bleeding [64].
Further studies are ongoing to help further our under-
standing in this area and will help refine our approach.
2.7. Secondary Risk Prevention after Acute
Myocardial Infarction
Following successful reperfusion therapies after acute
myocardial infarction, secondary risk prevention includ-
ing optimal blood pressure control, aggressive lipid low-
ering therapy, smoking cessation, weight reduction, ex-
ercise and participation in a cardiac rehabilitation pro-
gramme are important for improving outcomes. In a
meta-analysis by Clark et al. on secondary risk preven-
tion programmes, clear sustained mortality benefit (risk
ratio 0.85, 95% CI 0.77 - 0.94) was associated with these
programmes [65]. Further reductions in ischaemic events
are associated with aspirin and clopidogrel. Therefore
aspirin should be continued indefinitely and for clopido-
grel at least 3 - 12 months. The CURE trial demonstrated
that the evidence of benefit from clopidogrel begin to
emerge within 24 hours and sustained benefit was ob-
served up to 12 months in patients with acute coronary
syndrome [66]. Angiotensin converting enzyme (ACE)
inhibitors and angiotensin II receptor blockers has a role
in patients with heart failure, anterior infarction or his-
tory of previous infarction. Besides blood pressure con-
trol, these agents also have a role in reducing left ven-
tricular remodelling [67-69]. In patients with an ejection
fraction of less than 40% without severe renal dysfunc-
tion or hyperkalaemia, aldosterone antagonist has mor-
tality benefit and should be considered [70]. The benefit
of lipid lowering post acute myocardial infarctio n is well
understood. Patients should be counselled on non-phar-
macologic therapy such as exercise, weight reduction
and dietary modification. The role of statin therapy, in
particular high dose statins, at the time of diagnosis pro-
vides substantial reductions in mortality as well as non-
fatal ischaemic events [71]. Beta-blockers are also rec-
ommended after acute myocardial infarction with bene-
ficial effects on fewer recurrent myocardial infarctions
and episodes of ventricular fibrillation. However this
benefit has also been associated with increased risk of
cardiogenic shock [72]. In patients with severe left ven-
tricular dysfunction post acute myocardial infarction,
long acting beta-blockers such as bisoprolol, carverdilol
and metoprolol succinate should be considered. In the
CAPRICORN trial, carvedilol compared to placebo was
associated with lower all cause and cardiovascular mor-
tality when prescribed to patients with left ventricular
systolic dysfunction defined by EF < 40% [73].
Significant reductions in in-hospital, intermediate and
long-term outcomes in patients afflicted with acute myo-
cardial infarction have occurred as a result of th e additive
benefits of prompt mechanical revascularisation strate-
gies coupled with the administration of up-stream anti-
thrombotic and anti-platelet therapies. Newer anti-plate-
let agents have impacted upon rates of stent thrombosis,
however, at the expense of increased bleeding rates. It is
likely that a personalised approach to the chronic mana-
gement of thrombotic and bleeding risk in patients’ post-
AMI will yield optimal patient outcomes.
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