NSTEMI

(/eurointervention/textbook/pcr-textbook/table-of-contents/)
PART III CHAPTER 17 (http://www.stentforlife.com/)
INTERVENTIONS FOR ST-SEGMENT ELEVA-

TION ACUTE MYOCARDIAL INFARCTION
Dariusz Dudek, Carlo Di Mario, Giuseppe De Luca, Artur Dziewierz,
Tomasz Rakowski
CHAPTER UNDER UPDATE
SUMMARY
Early reperfusion therapy is a life-saving treatment for patients with ST-segment elevation myocardial infarction.
Primary PCI (percutaneous coronary intervention) is the preferred method of reperfusion. However, the advan-
tages of the invasive approach over fibrinolytic therapy may be reduced by late initiation of mechanical reperfu-
sion due to logistical problems related to transportation delay to a hospital with a 24/7 invasive service. To over-
come this limitation, regional programmes for coordination of the treatment of acute coronary syndromes are
being introduced based on the cooperation of a PCI-capable hospital (hub) with ambulances and non-PCI-capa-
ble hospitals (spokes). However, when the anticipated delay to primary PCI (percutaneous coronary interven-
tion) is longer than recommended, pre- or in-hospital fibrinolytic therapy should be administered as soon as
possible as a bridge to invasive treatment. PCI (percutaneous coronary intervention) technique, as well as ad-
junctive pharmacotherapy in ST-segment elevation myocardial infarction treatment, differ from standard PCI
(percutaneous coronary intervention) for stable angina due to the need for rapid intervention on thrombus con-
http://www.pcronline.com/eurointervention/textbook/pcr-textbook/chapter/current/108.html 17/05/16 11:13

Page 1 of 25
taining lesions, which increases the risk of complications including distal embolisation or no-reflow occurrence.
Aspiration thrombectomy, new stent designs and modern aggressive antiplatelet therapy have improved the im-
mediate and long-term results of primary PCI (percutaneous coronary intervention).
NETWORKING OF ACUTE MYOCARDIAL INFARCTION TREATMENT

The annual incidence of hospital admission for ST-segment elevation myocardial infarction (STEMI) varies be-
tween 44-142/100,000 (tel:44-142/100,000) individuals per year [1]. Reperfusion therapy is the most effective
method of STEMI (ST-elevation myocardial infarction) treatment. Primary percutaneous coronary intervention
(PCI) and thrombolysis represent two strategies of reperfusion. The relative use of these two strategies is differ-
ent across European countries. Importantly, in countries using mainly thrombolysis as a reperfusion strategy,
the overall rate of reperfusion therapy in STEMI (ST-elevation myocardial infarction) patients is lower than in
countries with a dominance of primary PCI (percutaneous coronary intervention) [1]. A major increase in prima-
ry PCI (percutaneous coronary intervention) utilization was observed in Europe during last years. According to
registry data from years 2010/2011 most countries has primary PCI (percutaneous coronary intervention) rate
around 400-600 procedures per million inhabitants (with the lowest number of 23 and highest number of 884
PCIs) [2] - ! Figure 1 (108_1905_figure1.png).
According to the European Society of Cardiology (ESC) Guidelines for STEMI (ST-elevation myocardial infarction)
treatment, primary PCI (percutaneous coronary intervention) is the preferred method of reperfusion, but only
when it is performed in a timely fashion by an experienced team [3, 4, 5]. Data from national registries show
that the recommended time delay from first medical contact (FMC) to primary PCI (percutaneous coronary in-
tervention) procedure is difficult to achieve, mainly due to the presentation of a large number of patients with
STEMI (ST-elevation myocardial infarction) in centres without an on-site primary PCI (percutaneous coronary in-
tervention) service [6, 7]. This is an important limitation of mechanical reperfusion (see also the paragraph on
timing issues). To overcome this limitation, the concept of networking was born which, by optimising the organi-
sation of STEMI (ST-elevation myocardial infarction) care, allowed an increase in the number of patients receiv-
ing mechanical reperfusion within the recommended time window. Well organised regional networks usually
cover an area of about 0.3 to 0.5 million inhabitants and consist of a PCI (percutaneous coronary intervention)
centre (hub), non-PCI hospitals (spokes) and the emergency medical systems. Networks covering larger popula-
tions also exist, especially when located in large metropolitan areas. According to European experience, the rec-
ommended population for one network is approximately 0.5 million inhabitants [8]. A smaller area provides a
lower number of STEMI (ST-elevation myocardial infarction) patients which decreases network effectiveness,
whereas in larger areas transportation, catheterisation facilities and coronary care unit beds may be overloaded
by the high number of patients. Typically, networks are centrally coordinated and have predefined transporta-
tion and treatment protocols which are important for reducing the time delay. Ideally, the coordinating centre
should provide training programmes and quality control with evaluation of outcome via local audits compared
with the general experience collected in, national registries). These are important tools to improve the system.
Only experienced, high-volume centres providing a 24/7 service should be part of a network because both oper-
ator volume and hospital volume influence primary PCI (percutaneous coronary intervention) results [9, 10].
This is very important for network planning in order to obtain optimal balance between the number of primary
PCI (percutaneous coronary intervention) centres and the number of inhabitants in the area of a particular net-
work (number of STEMI (ST-elevation myocardial infarction)) because both will influence the operator’s experi-
ence and time delay, which is important for treatment results.
Pre-hospital diagnosis of STEMI (ST-elevation myocardial infarction) allows bypassing the emergency room and
transferring the patients directly to the cathlab, which reduces the time to reperfusion [11, 12]. Electrocardio-
gram (ECG) interpretation can be done by the ambulance staff or via transmission from the ambulance to the
PCI (percutaneous coronary intervention) hospital or a central coordinating centre. This last modality can be
helpful when the ECG (electrocardiogram) interpretation is difficult, especially in paramedic-based ambulance
systems. In the many regions worldwide where ECG (electrocardiogram) teletrasmission has been implemented,
this system lead to a reduced time to mechanical reperfusion and facilitated the activation of cathlab staff, es-

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pecially during off-duty hours [13, 14]. Regional protocols for STEMI (ST-elevation myocardial infarction) net-
works differ within European countries according to specific local constraints [8, 15]. In some of them, pre-hos-
pital fibrinolysis was introduced as a bridge to mechanical reperfusion.
The STEMI (ST-elevation myocardial infarction) networking concept is actively promoted by the European “Stent
for Life” initiative ( >Link (http://www.pcronline.com/stentforlife/) ), in which the main goal is to promote me-
chanical reperfusion in Europe by reducing the time delay to reperfusion and increasing the number of patients
with STEMI (ST-elevation myocardial infarction) undergoing mechanical reperfusion. . During the last few years
many European countries have improved dramatically their rates of primary angioplasty implementing the
plans advised by the “Stent for Life” group, inspired by the experience of the best performing countries. The re-
cent survey on reperfusion strategies promoted as part of the “Stent for Life” initiative have shown that most
countries has reached the target penetration and a full supplement of EuroIntervention has been dedicated to
an individual analysis of the situation in individual countires and regions. ( >Eurointervention Volume 8 Supple-
ment P (http://www.pcronline.com/eurointervention/P_issue/) )
These principles have been adopted by the most recent ESC Guidelines for the management of acute myocar-
dial infarction in patients presenting with ST-segment elevation MI. They recommend that the prehospital man-
agement of STEMI (ST-elevation myocardial infarction) patients must be based on regional networks designed to
deliver reperfusion therapy expeditiously and effectively, with efforts made to offer primary PCI (percutaneous
coronary intervention) to as many patients as possible (recommendation Class I; level of evidence B). Primary
PCI-capable centres must deliver a 24/7 service and be able to start primary PCI (percutaneous coronary inter-
vention) as soon as possible but always within 60 min from the initial call (recommendation Class I; level of evi-
dence B). Patients transferred to a PCI-capable centre for primary PCI (percutaneous coronary intervention)
should bypass the emergency department and be transferred directly to the catheterization laboratory (recom-
mendation Class IIa; level of evidence B) [3].
TIMING ISSUES
There are a number of factors which may influence progression of myocardial necrosis during myocardial in-
farction (MI): completeness of coronary occlusion, presence of collateral circulation, pre- and post-conditioning,
individual myocardial oxygen demand. Despite the variability of these factors, duration of ischaemia remains
the most important determinant of infarct size and myocardial damage. It is widely accepted and recommend-
ed by current ESC guidelines that reperfusion therapy is indicated in all STEMI (ST-elevation myocardial infarc-
tion) patients <12 hours from chest pain onset (recommendation Class I; level of evidence A). Also, reperfusion
therapy (preferably primary PCI (percutaneous coronary intervention)) is indicated if there is evidence of ongo-
ing ischaemia, even if symptoms may have started >12 h beforehand or if pain and ECG (electrocardiogram)
changes have been stuttering.(recommendation Class I.; level of evidence C) [3]. Primary PCI (percutaneous
coronary intervention), which is the preferred reperfusion therapy, should be started in specific timeframes.
This might be difficult, due to logistical problems, when prolonged transfer to the centre with 24/7 invasive facil-
ities is necessary.
TIME DELAYS IN MYOCARDIAL INFARCTION

When analysing the timing of events in STEMI (ST-elevation myocardial infarction) treatment, several delay times
can be determined. The moment when the patient meets the medical system for the first time is called first
medical contact (FMC). The ischaemic time before FMC (first medical contact) is called delay between symptoms
onset and FMC (first medical contact) and this is mainly a patient-related delay, with improvements possible
only via education to recognise symptoms and timely call a unified number for the emergency service. At the
FMC (first medical contact) time point the initial diagnosis should be established and any further time delay is
related to the medical system. Another important moment is the start of reperfusion therapy, traditionally de-
fined byfirst balloon inflation or first thrombectomy catheter pass but now identitified from the wire passage
distal to the occluded segment. FMC (first medical contact) and door-to-needle time represent their equivalent

Page 3 of 25
when fibrinolytic therapy is given. These three time points (symptoms onset, FMC (first medical contact), first
wire passage with primary PCI (percutaneous coronary intervention) and needle time with fibrinolysis) are the
most important time-points in the diagnosis and treatment process in STEMI (ST-elevation myocardial infarc-
tion) patients. System-related delay times may be calculated from FMC (first medical contact) to hospital admis-
sion, cathlab admission, sheath insertion etc, but the most important is the time from FMC (first medical con-
tact) to first wire crossing since thrombectomy of direct stent implantation are often used instead of balloon
redilatation during PCI (percutaneous coronary intervention). For patients treated with fibrinolysis, the most im-
portant is the time from FMC (first medical contact) to needle (fibrinolytic therapy administration). The above-
mentioned time delays are also called door-to-balloon time and door-to-needle time. However, the “door” mo-
ment may not always be defined as “first door” (which equals FMC (first medical contact)), but can be hospital
door or cathlab door which gives a different time relation. Especially when analysing primary PCI (percutaneous
coronary intervention) compared to fibrinolysis, there is controversy that the clock for primary PCI (percuta-
neous coronary intervention) starts at the moment of FMC (first medical contact) but that for fibrinolysis it
starts after arrival at the hospital, which does not include any transportation delay. That is why it is better to use
FMC (first medical contact) for description of delay times. Details concerning delay times are described in ( !
Table 1 (108_1913_table1.png) ). Additionally, for primary PCI (percutaneous coronary intervention), the first bal-
loon/thrombectomy time point equates to the moment of reperfusion, whereas needle time equates to lysis de-
livery but precedes effective reperfusion.
IMPORTANCE OF DELAY TO MECHANICAL REPERFUSION

The relationship between reperfusion treatment delay and mortality has been studied extensively, mainly in
post hoc analyses based on observational data from randomised trials and registries. Early studies suggested
that the time dependency of mechanical reperfusion exists but it is less pronounced than in fibrinolysis. Zijlstra
et al demonstrated the relationship between time delay and mortality in fibrinolysis, but not in primary PCI-
treated patients [16]. Cannon et al found that mortality after primary PCI (percutaneous coronary intervention)
is not related to symptom onset-to-balloon time [17]. In a series of more than 1,300 patients Antoniucci et al
showed a positive correlation between time to treatment and mortality in high-risk patients but not in low-risk
patients [18]. Similarly, Brodie et al [19] demonstrated a significant relationship between time to treatment and
mortality only in high-risk patients with cardiogenic shock. However, De Luca et al [20], analysing long-term out-
come, found that there was a definite relationship between time delay to PCI (percutaneous coronary interven-
tion) treatment and 1-year mortality also in a general primary PCI (percutaneous coronary intervention) popula-
tion. Each 30 minutes of delay was associated with a relative risk increase of 7.5% at 1-year follow-up [20]. Simi-
larly, Nallamothu et al [21], based on GRACE (Global Registry of Acute Coronary Events) registry data, showed
that longer treatment delays were associated with higher 6-month mortality in both fibrinolysis and primary PCI
(percutaneous coronary intervention) patients. For primary PCI (percutaneous coronary intervention) patients,
6-month mortality increased by 0.18% per 10 minutes delay in door-to-balloon time between 90 and 150 min-
utes [21]. Observational studies showing the horizontal relationship between treatment delay and mortality af-
ter primary PCI (percutaneous coronary intervention) should be interpreted cautiously. Patients who present
early are more likely to be at high risk than late presenters [22]. Therefore, the apparent similarity of outcome
irrespective of time delay may only be the consequence of a worse a priori outcome of high-risk individuals
treated early and the better outcome of lower-risk patients treated later. Gersh et al has suggested that, in pa-
tients presenting late from symptoms onset, time delay to PCI (percutaneous coronary intervention) has a mini-
mal impact on mortality (plateau phase) [23]. The benefit of time delay reduction may not be similar in all pa-
tients but related to risk profile and time of presentation. For ethical reasons, it is impossible to assess properly
the role of reducing delay to mechanical reperfusion in a randomised fashion. However, based on current evi-
dence, it is recommended to make as much of an effort as possible to reduce delays to mechanical reperfusion.
PCI-RELATED DELAY

Page 4 of 25
Primary PCI (percutaneous coronary intervention) is the preferred form of reperfusion treatment for patients
with STEMI (ST-elevation myocardial infarction) [3, 4]. However, the advantages of an invasive approach over fib-
rinolytic therapy may be reduced by any additional delay to initiation of mechanical reperfusion due to logistical
problems. PCI-related delay is the additional delay necessary to perform primary PCI (percutaneous coronary
intervention) instead of fibrinolysis administration. This is the theoretical difference between the time of FMC
(first medical contact) to wire crossing minus the time from FMC (first medical contact) to the start of fibrinolytic
therapy. The maximum acceptable PCI-related delay, beyond which the benefit of primary PCI (percutaneous
coronary intervention) is completely counterbalanced by the harmful effect of reperfusion initiation delay, has
been analysed in many studies. The majority of them were trial-based but not individual patient-data-based
meta-analyses. Kent et al showed that a delay of 50 minutes as borderline yielded equivalent reductions in mor-
tality for both primary PCI (percutaneous coronary intervention) and thrombolysis [24]. In the analysis of Nal-
lamothu et al [25], the primary PCI (percutaneous coronary intervention) mortality benefit was lost if PCI-related
delay exceeded 88 minutes. Pinto et al [26] showed in a combined analysis of the NRMI-2, 3 and 4 that border-
line PCI-related delay was much longer, i.e, 114 minutes, and varied considerably depending on various factors
like duration of symptoms, age and infarction location. This suggests an individualised rather than a uniform ap-
proach for selecting an optimal reperfusion strategy. In the paper by Betriu et al [27], regression analysis
showed that the mortality rate for PCI (percutaneous coronary intervention) remained the same as that for fibri-
nolysis when the PCI-related time delay reached 110 minutes. De Luca et al [28] found equipoise between pri-
mary angioplasty and fibrinolysis at 180 minutes. Only one individual patient data meta-analysis by Boersma et
al [29] demonstrated that invasive treatment remains superior over fibrinolysis even for a PCI-related delay of
80-120 minutes (the analysis included only patients with a time delay <120 minutes). In the STREAM Study on
STEMI (ST-elevation myocardial infarction) patients presenting early (up to 3 hours from symptoms onset) with
an anticipated delay to PCI (percutaneous coronary intervention) longer than 60 minutes, despite a relative de-
lay to PCI (percutaneous coronary intervention) of 78 minutes early fibrinolysis was not associated with reduc-
tion of ischaemic events. Moreover, an increased rate of bleeding was found in patients randomised to fibrinoly-
sis arm [30].
Taking into account all these studies, current ESC guidelines recommend that a maximal PCI-related delay of
120 min, should be used in selecting primary PCI (percutaneous coronary intervention) over immediate throm-
bolysis as the preferred mode of reperfusion. However, as a target for quality assessment, primary PCI (percuta-
neous coronary intervention) should be performed within 90 min after FMC (first medical contact) in all cases.
In patients presenting early, with a large amount of myocardium at risk, the delay should be even shorter (≤60
min). In patients presenting directly in a PCI-capable hospital, the goal should also be to achieve primary PCI
(percutaneous coronary intervention) within 60 min of FMC (first medical contact) (recommendation Class I; lev-
el of evidence B) [3]. The organisation of STEMI (ST-elevation myocardial infarction) treatment strategy based on
anticipated delay to reperfusion is shown in ( ! Figure 2 (108_2637_figure2.jpg) ).
TIMING OF ANGIOGRAPHY AND PCI (PERCUTANEOUS CORONARY INTER-

VENTION) AFTER LYSIS
Routine angiography/PCI
Despite the progress made hitherto, challenges remain. The diffusion of STEMI (ST-elevation myocardial infarc-
tion) networks has reduced drastically the number of patients not treatable with primary PCI (percutaneous
coronary intervention). The remaining limited populations living too far from 24/7 hubs to receive primary PCI
(percutaneous coronary intervention) in time, however, are disadvantaged by not receiving the most efficacious
reperfusion treatment. To this can be added the additional disadvantage that the evidence gathered from the
seminal studies of the last decade is not applied routinely or in a timely fashion, and that no new major studies
have been conducted or new strategies designed recently. Research into new drugs for this acute indication
have also come to a stop in recent years. .

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In clinical trials from the 1980s and 1990s, immediate PCI (percutaneous coronary intervention) for STEMI (ST-
elevation myocardial infarction) following full-dose fibrinolysis (so-called facilitated PCI (percutaneous coronary
intervention)) was found to be associated with low angiographic efficacy and worse clinical outcome [31, 32].
This might depend on the lack of antiplatelet therapy and the increased prothrombotic state after fibrinolysis
[33, 34]. In the ASSENT-4 PCI (percutaneous coronary intervention) study [35], a strategy of immediate PCI (per-
cutaneous coronary intervention) after fibrinolysis was found to be harmful but many PCI (percutaneous coro-
nary intervention) procedures were performed at the time of maximal platelet activation after tenecteplase in
patients receiving a suboptimal antiplatelet therapy with only aspirin. Several studies were conducted to assess
the role and optimal moment of routine angiography/PCI after fibrinolysis. Some of those trials were conducted
based on additional transfer to a PCI (percutaneous coronary intervention) centre from non-PCI centres after
fibrinolysis administration. This strategy represents the so-called pharmaco-invasive approach when fibrinolysis
is administered as the initial reperfusion due to the anticipated delay to primary PCI (percutaneous coronary in-
tervention) caused by transfer logistics. In the SIAM III trial, a strategy of early angiography and immediate stent-
ing (3.5 ± 2.3 hours after fibrinolysis) was associated with a significant reduction of the combined endpoints of
death, reinfarction, target lesion revascularisation (TLR) and other ischaemic events after 30 days and 6 months
[36]. Similarly, in the GRACIA-1 study, after the mean time from fibrinolytic agent infusion to coronary angiogra-
phy of 16.7 ± 5.6 hours, the early angiography/PCI approach was associated with significant risk reduction of the
combined endpoint of death, non-fatal reinfarction and revascularisation at 1 year in comparison to the conser-
vative group [37]. In the CARESS in AMI (acute myocardial infarction) trial, transfer of high-risk STEMI (ST-eleva-
tion myocardial infarction) patients for early routine PCI (percutaneous coronary intervention) soon after the ad-
ministration of abciximab and half-dose reteplase was shown to reduce the risk of recurrent ischaemia and all
ischaemic complications at 30 days in comparison to conservatively treated patients with ischaemia-guided PCI
(percutaneous coronary intervention) (rescue PCI (percutaneous coronary intervention)). The median time from
fibrinolysis initiation to angiography in immediate PCI (percutaneous coronary intervention) group was 135 min-
utes [38]. Similarly, in the TRANSFER-AMI [39], enrolling high-risk STEMI (ST-elevation myocardial infarction) pa-
tients, the pharmaco-invasive strategy (immediate transfer for PCI (percutaneous coronary intervention) within
6 hours of fibrinolysis) was associated with better clinical outcome than standard treatment after fibrinolysis
with tenecteplase (rescue PCI (percutaneous coronary intervention) for failed reperfusion, with elective PCI (per-
cutaneous coronary intervention) encouraged for successfully reperfused patients after 24 hours). The median
time from fibrinolysis initiation to angiography was 3 hours. What is important is that all patients received as-
pirin, heparin, a loading dose of clopidogrel, and, in 73% of patients undergoing immediate PCI (percutaneous
coronary intervention), glycoprotein (GP) IIb-IIIa inhibitors [39]. In all the above-mentioned studies, no increase
in bleeding events was observed. The GRACIA-2 authors report that early routine post-fibrinolysis PCI (percuta-
neous coronary intervention) performed at 3–12 h after initiation of lytic therapy with the mean time to PCI (per-
cutaneous coronary intervention) of 6 h (median 4.6 hours) is safe, and results for myocardial perfusion better
than primary angioplasty [40]. The safety of PCI (percutaneous coronary intervention) early after fibrinolysis
was also confirmed in NORDISTEMI, with a high utilisation of a radial approach explaining the very low inci-
dence of access site complications [41]. In the meta-analysis of 7 clinical trials [35, 36, 37, 38, 39, 40, 42]compar-
ing early routine PCI (percutaneous coronary intervention) after fibrinolysis vs. standard therapy, lower rates of
reinfarction, death and reinfarction at 30 days and 6-12 months and recurrent ischaemia at 30 days were found
after early PCI (percutaneous coronary intervention). There was no difference in terms of stroke and major
bleedings between the groups [43].
After fibrinolysis routine coronary angiography and, if applicable, PCI (percutaneous coronary intervention) are
recommended by current ESC Guidelines (recommendation Class IIA (internal illiac artery); level of evidence A).
[3]. The caveat that a minimum time interval of 3 hours is required between fibrinolysis and PCI (percutaneous
coronary intervention) did not stand the test of the most recent trials confirming safety of PCI (percutaneous
coronary intervention) when performed with clopidogrel and/or GP IIb-IIIa inhibitors. Potentially, the newer
tienopirydine prasugrel and ticagrelor, both acting faster than clopidogrel, have advantages but they are unlike-
ly to be tested with fibrinolysis in sufficiently large trials to confirm their safety. It seems to be indisputable that
while promptly delivering fibrinolysis the operator should already be planning an immediate transfer to a cen-
tre with invasive facilities instead of waiting for fibrinolysis. The absence of negative effects of early angioplasty

Page 6 of 25
post-fibrinolysis was confimed by a subanalysis of one of the most recent PCI (percutaneous coronary interven-
tion) post-fibrinolysis trials [44]. No studies, however, convincingly demonstrate that a delay between fibrinoly-
sis and PCI (percutaneous coronary intervention) after successful reperfusion impairs outcome while the time
delay truly affecting prognosis also in these patients remains the time between start of symptoms of chest pain
and fibrinolysis.
Rescue angiography/PCI
Rescue PCI (percutaneous coronary intervention) for STEMI (ST-elevation myocardial infarction) is defined as in-
tervention performed on an infarct-related coronary artery after unsuccessful fibrinolysis. Accurate identifica-
tion of patients for whom fibrinolytic therapy has not restored IRA patency is still a problem in daily practice.
Such assessment is usually done 60-90 minutes after initiation of thrombolysis and is based on clinical symp-
toms (chest pain relief) and electrocardiographic ST-segment resolution (resolution >50% suggests successful
thrombolysis). Rescue PCI (percutaneous coronary intervention) strategy has been tested in clinical trials. In the
MERLIN (metabolic efficiency with ranolazine for less ischemia in non-) trial, 307 patients who failed to achieve
50% electrocardiographic ST-segment resolution at 60 minutes following fibrinolytic therapy were randomised
to either rescue PCI (percutaneous coronary intervention) or conservative treatment (without repeat administra-
tion of fibrinolytic therapy) [45]. There was no difference in mortality at 30 days, but a lower rate of composite
endpoint (death/reinfarction/stroke/subsequent revascularisation/heart failure) was observed in the rescue PCI
(percutaneous coronary intervention) arm [45]. The REACT trial enrolled 427 patients with <50% ST-segment res-
olution at 90 minutes and showed higher event-free survival at 6 months in patients treated with rescue PCI
(percutaneous coronary intervention) compared to those randomised to either fibrinolytic readministration or
conservative therapy [46]. In a meta-analysis of 8 trials including 1,177 patients, rescue PCI (percutaneous coro-
nary intervention) was associated with no significant reduction in all-cause mortality but showed significant risk
reduction in heart failure and reinfarction when compared with conservative treatment [47]. The effectiveness
of rescue angioplasty inspired the design of the STREAM trial, comparing in more than 1,800 patients primary
versus an active rescue strategy applied in patients receiving tenecteplase (followed by rapid transfer for rescue
PCI (percutaneous coronary intervention) in 36.9% of the patients) [30]. Despite the absence of overall differ-
ence in mortality in the two groups, the significant increase in intracranial bleeding in the fibrinolysis group
(dose had to be halved in patients over 75 years during the conduct of the trial) and the widespread availability
of primary PCI (percutaneous coronary intervention) make this alternative unappealing in clinical practice.
According to ESC Guidelines, rescue PCI (percutaneous coronary intervention) is indicated immediately when
fibrinolysis has failed (<50% ST-segment resolution at 60 min) (recommendation Class I; level of evidence A).
Emergency PCI (percutaneous coronary intervention) is indicated in the case of recurrent ischaemia or evidence
of reocclusion after initial successful fibrinolysis (recommendation Class I; level of evidence B). [3].
" FOCUS BOX 1

Angiography and PCI (percutaneous coronary intervention) for ST-segment elevation myocar-
dial infarction according to anticipated delay to mechanical reperfusion
Primary PCI (percutaneous coronary intervention) should be performed by an experienced
team as soon as possible after first medical contact (FMC)
The preferred time limit from FMC (first medical contact) to first balloon inflation should be
less than 90 minutes. This does not include:patients presenting early, with a large amount of
myocardium at risk where the delay should be ≤60 min and patients presenting directly in a
PCI-capable hospital where the delay should be ≤60 min.
Mechanical reperfusion and fibrinolysis are not alternative but complementary treatment
modalities. When primary PCI (percutaneous coronary intervention) is not available within
the recommended time (the best organisational model will fail to achieve this target in rural
or mountain areas far from primary PCI (percutaneous coronary intervention) centres) fibri-
nolysis should be administered immediately. Then the patient should immediately be trans-
ferred (to avoid further delays in case of persistent chest pain or ECG (electrocardiogram)
changes) to a PCI-capable hospital where angiography and PCI (percutaneous coronary inter-

Page 7 of 25
vention) should be performed within 24 hours
PROCEDURE TECHNIQUE
ACCESS SITE SELECTION

The selection of the coronary revascularisation method and the technique of performing primary PCI (percuta-
neous coronary intervention) are not significantly different from those routinely used during elective PCI (percu-
taneous coronary intervention). Femoral approach is commonly used, although in many centres a transradial
approach is widely used to decrease bleeding complications associated with aggressive antiplatelet and an-
tithrombotic treatment administered in the STEMI (ST-elevation myocardial infarction) setting. The femoral and
radial access techniques were described in detail in Chapter 1.04.
Importantly, the radial approach was shown to be associated not only with a reduction of acute bleeding events,
but also with a mortality reduction in STEMI (ST-elevation myocardial infarction) patients. Thus, according to cur-
rent ESC STEMI (ST-elevation myocardial infarction) Guidelines [3], the use of the radial access during primary
PCI (percutaneous coronary intervention) for STEMI (ST-elevation myocardial infarction) should be preferred, if
performed by an experienced radial operator (IIa; B). The transradial approach also allows for early ambulation
and reduction of total hospitalisation cost. The success rate of primary PCI (percutaneous coronary interven-
tion) via the transradial approach is similar to that observed with the femoral approach. Importantly, in experi-
enced centres, the use of radial access in the STEMI (ST-elevation myocardial infarction) setting is not associated
with prolongation of door-to-balloon time and procedure time [48, 49, 50]. On the other hand, the use of radial
access during more complex procedures is not ideal due to weaker guiding catheter back-up and the limited
possibility of larger than 6 Fr guiding catheters being used during the procedure, especially in radial arteries
with a small diameter (smaller women, patients with previous transradial procedures) [51]. Cardiogenic shock or
haemodynamic compromise should not be considered as absolute contraindications for the transradial ap-
proach, provided that the radial artery is palpable, possibly after insertion of an intra-aortic balloon pump (IABP)
via the femoral artery.
In a meta-analysis of 12 studies (randomised, case-control, and cohort studies) involving 3,324 patients the tran-
sradial approach during primary PCI (percutaneous coronary intervention) in comparison to femoral access was
associated with a significant reduction of major bleeding, death and the composite endpoint of death, MI, or
stroke. However, the fluoroscopic time was longer, and access site crossover was more frequent for the transra-
dial approach [52]. Physicians performing primary PCI (percutaneous coronary intervention) should be familiar
with the transradial approach, as it is also an approach of choice in patients with STEMI (ST-elevation myocardial
infarction) and concomitant severe peripheral vascular disease.
CATHETER AND GUIDEWIRE SELECTION

Coronary angiography can be performed with standard diagnostic catheters, although, angiography of the in-
farct-related artery can also be performed with a guiding catheter in order to save the time needed for catheter
exchange. The properties of different guiding catheters and guidewires are described in Chapter 3.03. Standard
Judkins and Extra Back-Up guiding catheters are preferred, but other guiding catheters (for example Amplatz),
selected based on orifice configuration, anatomy of the artery and location of atherosclerotic lesions, are useful
if a more effective guiding catheter back-up is needed. Proper guiding catheter selection increases the success
rate and decreases procedure time.
Passing through the site of occlusion should preferably be made with soft non-hydrophilic guidewires. Use of
soft guidewires limits the risk of distal vessel dissection and facilitates vessel true-lumen finding. If passage with
a soft guidewire is not successful, especially in calcified and tightly narrowed vessels, hydrophilic wires are the
second choice.

Page 8 of 25
" FOCUS BOX 2
Aspiration thrombectomy technique
Use of manual aspiration catheters should be recommended in occluded infarct-related ar-
teries or arteries with established distal flow and high thrombus burden after passing with
guidewire crossing
Successful thrombectomy allows better visualisation of the atherosclerotic lesion and distal
part of the infarct-related artery
Aspiration should be started 2 cm (centimeter) before the occlusion or the lesion with throm-
bus
Multiple slow-passage technique should be used, with a stop on the thrombus site and con-
tinuation of suction distally to the site of occlusion (if possible). Two or three passages are
recommended
The thrombectomy catheter must be removed with aspiration, even into the guiding
catheter, and then the blood from the guiding catheter must also be aspirated.
Suction success should be confirmed by presence of thrombus on the filter
If greater suction force is needed (bigger arteries, organised thrombus) larger size catheters
(7 Fr) or catheters with active thrombus fragmentation can be considered
PRIMARY PCI (PERCUTANEOUS CORONARY INTERVENTION) STRATEGY

Primary PCI (percutaneous coronary intervention) should be performed immediately after coronary angiogra-
phy within the culprit lesion. The optimal technique of primary PCI (percutaneous coronary intervention) should
be chosen after evaluation of IRA flow, thrombus burden and vessel size ( ! Figure 3 (108_1906_figure2.png) ).
Routine use of stents during primary PCI (percutaneous coronary intervention) for STEMI (ST-elevation myocar-
dial infarction) is currently recommended. Preferably, the technique of direct stenting (without prior balloon di-
latation) should be used if the distal part of the vessel is visible, as it is associated with improvement of reperfu-
sion parameters and a reduced risk of no-reflow phenomenon during primary PCI (percutaneous coronary in-
tervention) [53, 54, 55]. The use of simple manual aspiration catheters as an alternative to standard balloon di-
latation may facilitate direct stenting, especially in occluded arteries and vessels with large thrombus burden.
Recent ESC STEMI (ST-elevation myocardial infarction) guidelines recommended manual thrombectomy in STE-
MI (ST-elevation myocardial infarction) as Class IIa;B [3]. The strategy of mechanical protection and stent selec-
tion in different subsets of patients is described in the following paragraphs.
Only in the setting of cardiogenic shock is there a consensus for attempting multivessel PCI (percutaneous coro-
nary intervention) in selected patients with multiple critical lesions [3, 4]. Consecutive, haemodynamically signif-
icant lesions should be treated until haemodynamic stabilisation is achieved. Data concerning safety and effica-
cy of non-IRA revascularisation in non-shock patients during primary PCI (percutaneous coronary intervention)
in the acute setting are still limited. In two small randomised studies there was no excess of in-hospital and one-
year mortality and other cardiovascular (CV) events associated with non-IRA revascularisation during index pri-
mary PCI (percutaneous coronary intervention) [56, 57]. However, these studies were underpowered in order to
assess properly the potential differences in clinical events. In a more recent study from Politi et al, primary PCI
(percutaneous coronary intervention) limited to IRA was associated with decreased CV event-free survival com-
pared to patients treated with staged or simultaneous revascularisation of non-IRAs during the index proce-
dure. The recently published PRAMI trial observed a mortality benefit after immediate multivessel PCI (percuta-
neous coronary intervention) but the study was very controversial and far from being conclusive because all the
patients with culprit lesion only treatment were not triaged for presence and extent of residual ischaemia, and
then received suboptimal care [58]. By contrast, data from retrospective registries have shown conflicting re-
sults. Some have shown favourable [59], neutral [60, 61], and even worse outcomes including increased risk of
death [62, 63, 64, 65, 66] associated with non-IRA revascularisation during the index procedure. In the largest of
these, which included 3,134 patients treated with non-IRA PCI (percutaneous coronary intervention) during the
index procedure (from a total population of 28,936 patients with STEMI (ST-elevation myocardial infarction)), an

Page 9 of 25
increased in-hospital mortality was observed after routine multivessel PCI (percutaneous coronary intervention)
[62]. This difference in mortality persisted after adjustment for covariates only in patients with shock, and was
no longer significant in patients without shock. Meta-analysis [67]of randomised and non-randomised studies
(19 studies, 23 arms) which evaluated 61,764 subjects with STEMI (ST-elevation myocardial infarction) and multi-
vessel disease has shown that simultaneous non-IRA revascularisation in the acute setting of STEMI (ST-eleva-
tion myocardial infarction) is associated with an increase of 30-day mortality, without significant impact on long-
term mortality. On the other hand, staged, complete revascularisation during index hospital stay was associated
with a reduced risk of death and major adverse cardiac events (MACE) up to 30 days, as well as at 1 year [67].
THROMBECTOMY, PROXIMAL AND DISTAL PROTECTION

Suboptimal myocardial reperfusion may occur in a relatively large proportion of patients undergoing primary
PCI (percutaneous coronary intervention) for STEMI (ST-elevation myocardial infarction) despite optimal restora-
tion of epicardial flow, with subsequent unfavourable short and long-term outcome [68]. Among the factors ac-
counting for poor myocardial reperfusion after primary angioplasty, in recent years mounting interest has
emerged regarding the role of distal embolisation [69, 70] and therefore in mechanical devices to prevent such
a complication ( ! Table 2 (108_1914_table2.png) ).
Distal protection devices

Several distal protection devices ( ! Table 2 (108_1914_table2.png) , ! Figure 4 (108_1907_figure3.png) ) have
proved their beneficial effects in PCI (percutaneous coronary intervention) of saphenous venous bypass grafts.
Several randomised trials have been conducted in primary PCI (percutaneous coronary intervention).
A) Distal occlusive devices

The promising results with the PercuSurge (Medtronic, Inc, Minneapolis, MN, USA), observed in initial studies on
PCI (percutaneous coronary intervention) of saphenous venous bypass grafts, have not been confirmed in STE-
MI (ST-elevation myocardial infarction) by the large randomised EMERALD trial [71], where a total of 501 pa-
tients were randomised to PercuSurge GuardWire (Medtronic) (n=252) or conventional angioplasty (n=249). De-
spite atherothrombotic debris being found in 78% of patients, no benefits were observed in terms of myocar-
dial perfusion, whereas infarct size was paradoxically increased with the device. Similar findings were observed
in the ASPARAGUS [72] trial, where 341 patients were randomised to PercuSurge GuardWire (Medtronic) (n=173)
or conventional primary angioplasty (n=168). However, in both trials this device did not increase the risk of coro-
nary perforation or other mechanical complications.
B) Filters
The use of intracoronary filters ( ! Figure 4 (108_1907_figure3.png) ) has been shown to improve outcome in
elective patients undergoing elective PCI (percutaneous coronary intervention) of a saphenous venous bypass
graft. Also in this case, the promising results observed with initial non-randomised trials have not been con-
firmed by randomised trials. In the PROMISE trial [73], 200 patients were randomised to FilterWire EZ™ (Boston
Scientific, Natick, MA, USA) or conventional angioplasty. The use of filters did not lead to improvements in terms
of myocardial perfusion (as evaluated by Doppler flow wire) and infarct size (as evaluated by cardiac magnetic
resonance).
A pooled analysis of all trials on distal protection devices (7 trials, with a total of 1,353 patients)[74]showed that
despite benefits in terms of myocardial perfusion (myocardial blush grade (MBG) 3: 50.2% vs. 39%, odds ratio
(OR) = [95% confidence interval (CI)] = 1.96 [1.18-3.26], p=0.009 (random effect model), phet = 0.02), no advan-
tages were observed in terms of 30-day mortality (2.0% vs. 3.4%, OR (odds ratio) [95% CI] = 0.61 [0.3-1.25],
p=0.18 (random effect model), phet = 0.92) ( ! Figure 5 (108_1909_figure5.png) ).
Proximal protection devices

The Proxis Embolic Protection System (Velocimed, Maple Grove, MN, USA), has recently been introduced to ob-
tain complete protection from distal embolisation during PCI (percutaneous coronary intervention). In fact, this
system may overcome some of the limitations of distal protection devices, such as the need of a distal “landing
zone” of adequate calibre, incomplete protection in the case of large branches proximal to the distal protection

Page 10 of 25
device, and difficulties due to a complex anatomy such as vessel tortuosity or calcifications. This catheter, in
fact, is deployed proximally to the target lesion, with complete interruption of antegrade blood flow before
crossing the lesion. Unlike distal protection devices, this system is able to retrieve embolic materials of any size
and composition.
In the PREPARE trial [75], Haeck et al have randomised 141 STEMI (ST-elevation myocardial infarction) patients
to PROXIS and 143 to conventional primary PCI (percutaneous coronary intervention). Despite significant advan-
tages in terms of immediate ST-resolution (66% vs. 50%, p=0.009), no difference was observed in terms of ST-
resolution at 90 minutes (81% vs. 74%, p=0.23), MBG (myocardial blush grade) 3 (81% vs. 83%, p=0.93), distal
embolisation (10% vs. 14%, p=0.36) and clinical outcome. Future larger trials are certainly needed to evaluate
the benefits in terms of myocardial perfusion and clinical outcome with this device.
Thrombectomy devices
The use of thrombectomy devices ( ! Figure 6 (108_1910_figure6.png)) seems attractive to overcome some of
the limitations of distal protection devices, such as the need of a “landing zone” and to cross the lesion which
may cause distal embolisation. Several thrombectomy devices have been proposed to prevent distal embolisa-
tion, such as AngioJet® (Medrad Inc, Minneapolis, MN, USA), X-SIZER® (eV3, Inc, Plymouth, MN, USA), Rescue
(Boston Scientific-Scimed, Inc, Maple Grove, MN, USA – not in use anymore), Export® Catheter (Medtronic Inc,
Santa Rosa, CA, USA), Diver C.E.® (Invatec S.p.a, Roncadelle, Italy), Pronto® Catheter (Vascular Solutions, Inc,
Minneapolis, MN, USA), Rinspiration® System (Kerberos Proximal Solutions, Cupertino, CA, USA), TVAC (Throm-
bus vacuum aspiration catheter; Nipro, Osaka, Japan), Eliminate (Terumo, Tokyo, Japan), Fetch-2® (Medrad Inc.,
Minneapolis, MN, USA), XpressWay ® (Kaneka, Osaka, Japan), QuickCat® extraction catheter (Spectranetics, Col-
orado Springs, CO, USA) ( Figure 6 ).
Several trials have been conducted with different devices leading to conflicting results. Mostly negative results
have been observed in two large trials with mechanical thrombectomy [76, 77].
In the AIMI multicentre trial [76], a total of 480 patients were randomised to rheolytic thrombectomy with Angio-
Jet® (Medrad Inc.) vs. conventional primary PCI (percutaneous coronary intervention). The primary endpoint
was infarct size estimated by technetium-99m sestamibi. Paradoxically this trial showed a larger infarct size and
higher mortality in patients treated with thrombectomy in comparison with conventional primary PCI (percuta-
neous coronary intervention). However, several factors may explain the negative results of this trial, including
the low rate of anterior infarction (around 35%), a larger unjustified use of a temporary pacemaker in patients
randomised to thrombectomy (58% vs. 19%), the large prevalence of preprocedural recanalisation (preprocedur-
al thrombolysis in myocardial infarction (TIMI) 3 flow was more frequently observed in the control group [27]
than in patients randomised to thrombectomy [19]), and the very low rate of patients with evidence of throm-
bus.
In a Danish single-centre trial [77], a total of 215 STEMI (ST-elevation myocardial infarction) patients were ran-
domised to mechanical thrombectomy by the Rescue catheter (Boston Scientific-Scimed) or conventional prima-
ry angioplasty. Also in this study, patients were not selected on the basis of angiographic evidence of thrombus.
Enzymatic infarct size, the primary study endpoint, was, in accordance with the AIMI trial, paradoxically larger in
patients randomised to thrombectomy. No benefits were observed in terms of ST-segment resolution.
Different findings have been observed in the recently conducted JETSTENT trial [78], where the AngioJet® was
tested in patients with large thrombotic burden. The device was associated with a significant improvement in
ST-segment resolution (primary endpoint) and MACE (major adverse cardiac events) at 6 months, even though
no difference was observed in scintigraphic infarct size (primary endpoint). A pooled analysis of RCTs on me-
chanical devices did not show better quality reperfusion, and despite improvement in ST-segment resolution,
no difference was observed in mortality ( ! Figure 5 (108_1909_figure5.png) ) [79].
Several randomised studies have shown that manual thrombectomy devices significantly improve myocardial
perfusion (evaluated by MBG (myocardial blush grade) and ST-segment resolution) and reduce distal embolisa-
tion.

Page 11 of 25
In the large TAPAS trial [80], more than 1,000 STEMI (ST-elevation myocardial infarction) patients were ran-
domised before angiography to routine manual thrombectomy (Export Catheter; Medtronic) or conventional
primary PCI (percutaneous coronary intervention). The vast majority of patients received GP IIb-IIIa inhibitors.
This study showed significant benefits in myocardial perfusion (evaluated by MBG (myocardial blush grade) and
ST-segment resolution) and significant benefits in one-year survival with manual thrombectomy.
In a first meta-analysis of 9 randomised trials on manual thrombectomy devices including 2,401 patients [81],
manual thrombectomy devices were associated with significant benefits in 30-day survival, explained by the im-
provement of epicardial and myocardial perfusion and reduction in distal embolisation However, the benefits
seemed to be less pronounced in a more updated meta-analysis (Figure 5) [79]
The beneficial effects from manual thrombectomy have not been confirmed by the recently published large
TASTE randomized trial [82]. In fact at 30-day follow-up death from any cause occurred in 2.8% of the patients in
the thrombus-aspiration group (103 of 3,621), as compared with 3.0% in the PCI-only group (110 of 3,623) (haz-
ard ratio, 0.94; 95% confidence interval [CI], 0.72 to 1.22; p=0.63). No significant differences were observed be-
tween the groups with respect to the rate of stroke or neurologic complications at the time of discharge
(p=0.87). However, the study nested in a registry approach of this Swedish group did not prevent the exclusion
of about 40% of the initial screened population,contributing to a large selection bias. In fact, with a mortality
rate as low as 3%, we could have not expected so much absolute beneficial effects. Finally, the study was con-
ducted as a registry, without any event verification, especially for any secondary endpoint.
In conclusion, randomised trials conducted so far on mechanical thrombectomy devices have failed to show
benefits in terms of infarct size and myocardial perfusion. The TASTE trial, the largest trial so far conducted, has
recently questioned the beneficial effects from routine manual thrombectomy devices. The large TOTAL trial, in-
cluding more than 10,000 STEMI (ST-elevation myocardial infarction) patients, will provide important informa-
tion to clarify the role of routine thrombectomy in primary angioplasty. However, independently from the con-
clusions of this additional trial, unless harmful effects emerge, a thrombus-based strategy may still be suggest-
ed, with the use of thrombectomy in cases of absent preprocedural recanalisation or presence of angiographi-
cally-evident coronary thrombus, thus favouring direct coronary stenting. The use of mechanical devices may
certainly be considered in cases of large, extensive thrombus burden.
STENT SELECTION (BARE METAL, DRUG-ELUTING, MESH-COVERED

STENTS)
A previous meta-analysis of patients undergoing primary PCI (percutaneous coronary intervention) has shown
the benefits of stenting compared to balloon angioplasty alone in terms of reducing target vessel revascularisa-
tion (TVR), though no definite impact on death and reinfarction was present [83].
Several randomised trials have been conducted so far on drug-eluting stents (DES) in STEMI (ST-elevation my-
ocardial infarction), and long-term follow-up data have recently been published. Tebaldi et al [84], recently re-
ported 5-year follow-up from the STRATEGY trial, where sirolimus-eluting stent (SES) plus tirofiban was com-
pared to bare metal stent (BMS) BxVelocity® (Cordis, Johnson & Johnson, Warren, NJ, USA) plus abciximab in
175 STEMI (ST-elevation myocardial infarction) patients. At 5 years, the cumulative incidence of MACE (major ad-
verse cardiac events) (death, MI, or TVR (Target vessel revascularisation)) showed a lower trend in the tirofiban-
SES group (29.9% vs. 43.2%, p=0.067). All-cause mortality and the composite of death or MI were similar in the
tirofiban-SES versus the abciximab-BMS group, whereas the need for TVR (Target vessel revascularisation) re-
mained markedly reduced (10.3% vs. 26.1%, p=0.007) in the tirofiban-SES group. The benefits from SES
(sirolimus-eluting stent) in terms of reducing clinical and angiographic restenosis without an increase in death
or MI have been confirmed at long-term follow-up (4 and 3 years) in subsequent moderate-sized randomised
trials such as the TYPHOON [85]and SESAMI [86] trials, respectively.

Page 12 of 25
In the PASSION trial [87], a paclitaxel-eluting stent (PES) was compared to the EXPRESS™ stent (Boston Scientif-
ic, Maple Grove, MN, USA) in 619 STEMI (ST-elevation myocardial infarction) patients. Despite the safety of PES
(paclitaxel-eluting stent) in terms of death and stent thrombosis as compared to BMS (bare metal stent), at 5-
year follow-up only a weak trend was present towards a reduction in TVR (Target vessel revascularisation) (7.3%
vs. 10.5%, p=0.16). The relatively less favourable outcomes of PES (paclitaxel-eluting stent) in this trial compared
to SES (sirolimus-eluting stent) in the previous trials may relate to either the less marked reduction of neointi-
mal hyperplasia with paclitaxel compared to sirolimus or a better outcome with the control stent in the PAS-
SION trial compared to the Bx Velocity® (Cordis) in the SES (sirolimus-eluting stent) trials. Also of note, routine
angiographic follow-up was not performed in the PASSION trial.
Data from the PASEO trial [88] showed that at 5-year follow-up both SES (sirolimus-eluting stent) and PES (pacli-
taxel-eluting stent) were equally associated with a significant reduction in TVR (Target vessel revascularisation)
and MACE (major adverse cardiac events), without any concern in terms of death and in-stent thrombosis.
Some words of caution recently came from the DEDICATION trial [89], where a significant reduction in TVR (Tar-
get vessel revascularisation) (8.9% vs. 19.8%), but a significantly higher risk of cardiac death with DES (drug-elut-
ing stent) as compared to BMS (bare metal stent) (6.1% vs. 1.9%, p=0.013), was observed at 3-year follow-up.
Two-year follow-up data of the HORIZONS-AMI trial [90] have recently been published. Compared with BMS
(bare metal stent), PES (paclitaxel-eluting stent) showed similar outcome in terms of death, reinfarction and in-
stent thrombosis, while the 24-month TLR (Target lesion revascularisation) rate was significantly reduced from
14.2% to 8.3% (p<0.0001). The difference was more pronounced in patients undergoing routine angiographic
follow-up [90]and in patients with identified high-risk features for TLR (Target lesion revascularisation), such as
insulin-treated diabetes mellitus, reference vessel diameter ≤3.0 mm (millimetre), and lesion length ≥30 mm
(millimetre). In patients with 2 or 3 of these baseline risk factors, PES (paclitaxel-eluting stent) compared with
BMS (bare metal stent) markedly reduced 12-month TLR (Target lesion revascularisation) (19.8% vs. 8.1%,
p=0.003), with only modest benefits in patients with 1 of these risk factors (7.3% vs. 4.3%, p=0.02) and no bene-
fits in patients with no risk factor (3.3% vs. 3.2%, p=0.93).
A recent meta-analysis (DESERT) based on individual data with long-term follow-up from 6,298 patients [91]
showed, at a mean follow-up of 3 years, that 1st generation DES (drug-eluting stent) significantly reduced TVR
(Target vessel revascularisation) compared with BMS (bare metal stent), without increasing mortality, reinfarc-
tion and overall stent thrombosis. However, very late reinfarction and stent thrombosis, occurring 1 year after
revascularisation, were significantly increased with DES (drug-eluting stent).[92]Large interests have been re-
cently focused on new generation DES (drug-eluting stent), with more biocompatible polymer, bioabsorbable
polymers, or even polymer-free. In fact, it was well known that the polymer was, due to persistent inflamma-
tion, one of the determinants of late stent thrombosis. Several trials have been conducted in the setting of STE-
MI (ST-elevation myocardial infarction).
The COMFORTABLE-AMI [93] compared the biolimus-eluting stent with biodegradable polymer (BES) vs BMS
(bare metal stent) in 1,500 patents. At 1-year follow-up major adverse cardiac events occurred in 24 patients
(4.3%) receiving BES (biolimus-eluting stent) and 49 patients (8.7%) receiving BMS (bare metal stent) (p=0.004).
The difference was driven by a lower risk of target vessel-related reinfarction (0.5% vs. 2.7%, p=0.01) and is-
chemia-driven TLR (Target lesion revascularisation) (1.6% vs. 5.7%, p<0.001) in patients receiving BES (biolimus-
eluting stent) compared with those receiving BMS (bare metal stent).
In the EXAMINATION trial [94] 1,498 patients with STEMI (ST-elevation myocardial infarction) were randomly as-
signed to receive EES (everolimus-eluting stent) or BMS (bare metal stent). At 1-year follow-up the primary end-
point (patient-oriented combined endpoint of all-cause death, any recurrent myocardial infarction, and any
coronary revascularisation) was similar in both groups (11.9% in the EES (everolimus-eluting stent) group vs.
14.2% in the BMS (bare metal stent) group; p=0.19. However, EES (everolimus-eluting stent) was associated with
significantly lower rates of target- lesion and vessel revascularisation (2.1% vs. 5.0%, p=0.003, and 3.7% vs. 6.8%,
p=0.0077) and stent thrombosis (0.5% vs. 1.9% for definite and 0.9% vs. 2.5% for combined definite or probable
stent thrombosis, both p=0.019).

Page 13 of 25
In the XAMI (XienceV Stent vs Cypher Stent in Primary PCI (percutaneous coronary intervention) for Acute My-
ocardial Infarction) [95] trial a total of 625 patients with AMI (acute myocardial infarction) were randomised (2:1)
to receive EES (everolimus-eluting stent) or SES (sirolimus-eluting stent). Primary endpoint was major adverse
cardiac events (MACE) at 1 year consisting of cardiac death, nonfatal MI, or any TVR (Target vessel revascularisa-
tion). EES (everolimus-eluting stent) was associated with a significant reduction in the primary endpoint (4% vs.
7.7%, p=0.048), whereas no difference was observed in terms of cardiac mortality (1.5% vs. 2.7%, p = 0.36), and
definite and/or probable stent thrombosis (1.2% vs. 2.7%, p=0.21).
The beneficial effects and a significant reduction in stent thrombosis with new generation DES (drug-eluting
stent) have been confirmed in a recent network meta-analysis [96].
Keeping in mind the higher initial costs, and the potential higher risk of late in-stent thrombosis, especially
when the stent is implanted in a thrombotic environment, it may be reasonable to implant a DES (drug-eluting
stent) in selected STEMI (ST-elevation myocardial infarction) patients at high risk for restenosis, such as long le-
sions, small vessels, left main, and diabetes. It is strongly recommended in case of DES (drug-eluting stent) im-
plantation:
Forecast the compliance to long-term dual antiplatelet therapy.

Avoid stent implantation in the presence of residual thrombus. Thrombectomy is strongly encouraged in
order to avoid, after thrombus dissolution, late stent malapposition. Furthermore, thrombus removal
may reduce vasospasm associated with platelet humoral factors and therefore help to evaluate the right
vessel size. Nitrate administration is strongly encouraged to reduce vasospasm further.
The use of DES (drug-eluting stent) should be avoided in case of complex, calcified lesions, where the optimal
stent expansion may be compromised, in case of residual intracoronary thrombus, in patients with out-of-hos-
pital cardiac arrest.
In case of large thrombus burden, the use of a mesh-covered stent may be considered to trap the thrombus
and reduce distal embolisation. Recent experiences [97, 98, 99] showed the safety of MGuard™ (MGS, Inspire-
MD, Tel Aviv, Israel) implantation in the setting of primary PCI (percutaneous coronary intervention). In a recent
randomised trial [100] a total of 433 patients with STEMI (ST-elevation myocardial infarction) presenting within
12 hours of symptom onset undergoing PCI (percutaneous coronary intervention) were randomized to the
MGuard (n=217) or commercially available BMS (bare metal stent) or DES (drug-eluting stent) (n=216). The pri-
mary endpoint was the rate of complete (≥70%) ST-segment resolution measured 60 to 90 min post-procedure,
which was significantly improved in the patients randomised to the MGuard stent compared with control pa-
tients (57.8% vs. 44.7%, p=0.008). MGuard stent resulted in superior rates of Thrombolysis In Myocardial Infarc-
tion 3 flow (91.7% vs. 82.9%, p=0.006), with a trend towards reduction in mortality (0% vs. 1.9%, p=0.06). In addi-
tion, great interest has been focused in recent years on self-expanding nitinol stents, such as Stentys (Stentys
S.A, Paris, France). In fact, this may potentially overcome the risk of late stent malapposition and reduce the risk
of distal embolisation. A recent study including 25 STEMI (ST-elevation myocardial infarction) patients treated
with Stentys [101] showed by intravascular ultrasound a significant vasodilatation distal to the culprit lesion at
three-day follow-up (+19%), with a similar expansion of the implanted stent (+18%), without any cases of late
stent malapposition at six months. Future randomised trials are certainly needed to demonstrate clinical bene-
fits from this stent.
IABP & LEFT VENTRICULAR ASSIST DEVICES

Based on current guidelines [3], the use of an IABP (intra-aortic balloon pump) in the acute setting of STEMI (ST-
elevation myocardial infarction) may be considered only in the presence of cardiogenic shock– IIb B recommen-
dation. This recommendation is supported by results of a meta-analysis of 7 randomised studies on STEMI (ST-
elevation myocardial infarction) patients [102]. In this meta-analysis, routine use of IABP (intra-aortic balloon
pump) in non-shock STEMI (ST-elevation myocardial infarction) patients showed neither a 30-day survival bene-
fit nor improved left ventricular ejection fraction, while being associated with significantly higher stroke and
bleeding rates [102]. Similarly, in the CRISP AMI (acute myocardial infarction) study, the routine use of IABP (in-

Page 14 of 25
tra-aortic balloon pump) during primary PCI (percutaneous coronary intervention) among patients with acute
anterior STEMI (ST-elevation myocardial infarction) without shock was not associated with reduction of infarct
size assessed by cardiac magnetic resonance [103]. It should be stressed that IABP (intra-aortic balloon pump) is
contraindicated in patients with severe aortic insufficiency or aortic dissection. Importantly, based on the results
of IABP-SHOCK II study the routine use of IABP (intra-aortic balloon pump) even in patients with cardiogenic
shock is questioned. In this study, no difference in 30-day as well as 12-month mortality was observed between
patients with cardiogenic shock treated with and without IABP (intra-aortic balloon pump) [104, 105].
Several other left ventricular assist devices which can be inserted percutaneously have been tested in the STEMI
(ST-elevation myocardial infarction) setting. However, the use of percutaneous centrifugal pumps [106] (Tandem
Heart; Cardiac Assist, Inc, Pittsburgh, PA (pulmonary artery), USA) and microaxial propeller pumps (Impella;
Abiomed, Inc, Danvers, MA, USA) [107] was not associated with significant 30-day mortality reduction, despite
initial early haemodynamic recovery in shock patients. A meta-analysis summarising the data of 100 patients
from three randomised clinical trials showed no difference in 30-day mortality and a trend towards more ad-
verse events, such as bleeding and vascular complications in the group receiving percutaneous assist devices
[108]. According to ESC/EACTS guidelines on myocardial revascularisation, routine use of percutaneous centrifu-
gal pumps was not recommended (recommendation Class III; level of evidence B) [4]. However, left ventricular
assist devices may be considered for circulatory support in patients with STEMI (ST-elevation myocardial infarc-
tion) in refractory shock (IIb; C) [3].
ADJUNCTIVE PHARMACOTHERAPY
ANTIPLATELET THERAPY BEFORE, DURING AND AFTER ANGIOPLASTY

Optimal inhibition of platelet aggregation is essential in STEMI (ST-elevation myocardial infarction) patients un-
dergoing mechanical reperfusion. In addition to acetylsalicylic acid, several therapies have been proposed in the
acute and chronic phase.
P2Y12 inhibitors
Clopidogrel
Clopidogrel, a second-generation thienopyridine which irreversibly binds to an adenosine diphosphate P2Y12
receptor, has largely replaced the first-generation thienopyridine (ticlopidine) due to its similar efficacy but bet-
ter tolerability profiles. Despite the absence of clinical trials specific to the STEMI (ST-elevation myocardial infarc-
tion) population, combination therapy including aspirin and clopidogrel is considered the standard of care for
patients receiving primary PCI (percutaneous coronary intervention). Several strategies have been evaluated in
patients undergoing PCI (percutaneous coronary intervention) to overcome some limitations of clopidogrel, es-
pecially in the settings of primary PCI (percutaneous coronary intervention), including slow onset of action and
large inter-patient variability. Enhancing the loading dose of clopidogrel (600-900 mg (milligramme)) shortens
the delayed onset of platelet inhibition compared to a 300 mg (milligramme) loading dose of clopidogrel and re-
duces the rate of suboptimal responders and further decreases the release of troponin prior to PCI (percuta-
neous coronary intervention) [109]. The same results were found in patients undergoing PCI (percutaneous
coronary intervention) and treated chronically with clopidogrel [110]. More details concerning the phenomenon
of non-response to clopidogrel and its clinical relevance are provided in Chapter 3.25. The effects of a high load-
ing dose (600 mg (milligramme) vs. 300 mg (milligramme)) and a maintenance dose (150 mg (milligramme) vs.
75 mg (milligramme)) have recently been shown to provide benefits in terms of thrombotic complications. More
recent ESC guidelines on PCI (percutaneous coronary intervention) [4], recommend (recommendation Class I;
level of evidence C) the administration of a 600 mg (milligramme) loading dose of clopidogrel in STEMI (ST-eleva-
tion myocardial infarction) patients who are clinically eligible for primary PCI (percutaneous coronary interven-
tion) at the FMC (first medical contact). After primary PCI (percutaneous coronary intervention), 75 mg (mil-
ligramme) of clopidogrel is recommended for up to 12 months in association with aspirin (recommendation
Class I; level of evidence A).

Page 15 of 25
Third-generation thienopyridine: Prasugrel
In order to overcome the evident limitations of clopidogrel, new oral adenosine diphosphate antagonists have
recently been developed. Prasugrel is still a prodrug, as much as clopidogrel. However, its shorter metabolic
pathway increases the efficacy of the drug, which is able to obtain a faster and more complete inhibition of
platelet aggregation as compared to clopidogrel. The randomised, double-blind TRITON-TIMI 38 trial included
13,608 patients with acute coronary syndrome eligible for PCI (percutaneous coronary intervention) and pa-
tients were randomised to receive either prasugrel (60 mg (milligramme) loading dose plus maintenance at 10
mg/day) or clopidogrel (300 mg (milligramme) loading dose plus maintenance at 75 mg/day) on top of aspirin.
In the STEMI (ST-elevation myocardial infarction) cohort [111] (3,534 patients undergoing primary PCI (percuta-
neous coronary intervention) [within 12 h of onset of symptoms] or secondary PCI (percutaneous coronary in-
tervention) [12 h to 14 days after onset of symptoms]), prasugrel was superior to clopidogrel in the primary
endpoint (a composite of CV death, non-fatal MI, or non-fatal stroke) at both 30 days (hazard ratio [HR] 0.68,
95% CI: 0.54–0.87, p=0.002) and 15 months (HR 0.79, 95% CI: 0.65–0.97, p=0.019) ( ! Figure 7 (108_1911_fig-
ure7.png) ).
The incidence of definite or probable stent thrombosis, as defined by Academic Research Consortium criteria,
was also significantly lower with prasugrel at both 30 days and 15 months. In contrast to the overall study popu-
lation, the incidence of TIMI (thrombolysis in myocardial infarction) major bleeding unrelated to coronary artery
bypass grafting (CABG) in the STEMI (ST-elevation myocardial infarction) cohort did not differ significantly be-
tween prasugrel and clopidogrel at 30 days (HR 0.74, 95% CI: 0.39–1.38, p=0.34) or 15 months (HR 1.11, 95% CI:
0.70–1.77, p=0.65).
Ticagrelor
The oral, reversible P2Y12 receptor antagonist ticagrelor is the first of a new chemical class of antiplatelet
agents, the cyclopentyl-triazolo-pyrimidines. Unlike the thienopyridines, ticagrelor reversibly blocks the platelet
P2Y12 receptor. This agent allows for a nearly complete inhibition of adenosine diphosphate-induced platelet
aggregation ex vivo and as a direct-acting compound does not require any metabolic activation.
In the PLATO (platelet inhibition and patient outcomes) randomised trial [112], including about 18,000 moderate
to high-risk acute coronary syndrome patients, including STEMI (ST-elevation myocardial infarction) scheduled
for primary PCI (percutaneous coronary intervention), ticagrelor at a dose regimen of 180 mg (milligramme) fol-
lowed by 90 mg (milligramme) BID dose has been shown to provide, as compared to clopidogrel (300/600 mg
(milligramme) loading dose / 75 mg (milligramme) maintenance dose), significant benefits in terms of mortality
and in-stent thrombosis, without increasing the risk of major bleeding complications. The results have been
confirmed in the STEMI (ST-elevation myocardial infarction) cohort of patients [113] ( ! Figure 8 (108_1912_fig-
ure8.png) ).
Prasugrel vs. ticagrelor

Small randomised trials have compared the pharmacodynamic effects of ticagrelor vs prasugrel in STEMI (ST-
elevation myocardial infarction) patients undergoing primary angioplasty, showing no significant difference be-
tween the two groups [114, 115, 116]. There are no studies directly testing the impact of ticagrelor vs. prasugrel
on outcome in patients with STEMI (ST-elevation myocardial infarction). An adjusted indirect comparison meta-
analysis [117] of prasugrel versus ticagrelor for patients with acute coronary syndromes (three trials with 32,893
patients included) have shown that both drugs are superior to clopidogrel for acute coronary syndrome. Head-
to-head comparison suggests similar efficacy and safety of prasugrel and ticagrelor, but prasugrel appears
more protective against stent thrombosis, while causing more bleedings. However, the risk of major bleeding
not related to bypass surgery was similar for both drugs. An ongoing large randomised trial (ISAR-REACT 5) will
hopefully provide more information on this issue [118].
Cangrelor
Cangrelor is an intravenous ADP (adenosine diphosphate) antagonist with quick fast-on and fast-off effects (due
to rapid reversibility). This drug is of potential interest for STEMI (ST-elevation myocardial infarction). In fact, sev-
eral recent studies have shown that even new oral ADP (adenosine diphosphate) antagonists have a delay in on-
set of action, with less than 50% of patients with optimal inhibition at 2 hours and peak effect that may be ob-

Page 16 of 25
served later than 4 hours after administration. No randomised trials have strictly been conducted in the setting
of STEMI (ST-elevation myocardial infarction). However, the large CHAMPION series, including also STEMI (ST-ele-
vation myocardial infarction) patients in CHAMPION PCI (percutaneous coronary intervention) and CHAMPION
Phoenix, showed by pooled analysis a significant reduction in stent thrombosis at 30 days (0.9% vs 1.3%,
p=0.0027) [119]. Future large trials are certainly needed to evaluate the safety and benefits of cangrelor in pri-
mary PCI (percutaneous coronary intervention), especially as upstream therapy with the aim of early recanaliza-
tion, in the era of new oral ADP (adenosine diphosphate) antagonists.
Glycoprotein IIb-IIIa inhibitors

Among the three molecules ( ! Table 3 (108_1904_table3.png) ), most of the trials have been focused on abcix-
imab, showing that its adjunctive administration may reduce the risk of mortality and reinfarction [120]. The use
of this therapy has waned by the introduction of new ADP-antagonists. However, recent data have clearly
shown a delayed onset of action of both prasugrel and ticagrelor [121], and therefore have renewed the interest
for GP IIb-IIIa inhibitors. Time-to-treatment has been shown to have a negative impact on survival even with me-
chanical reperfusion [20], and therefore further benefits may be expected from early pharmacological reperfu-
sion. Despite the negative results of the largest trial so far conducted, the FINESSE trial [122], an individual pa-
tient’s data meta-analysis of several randomised trials [123], and several registries [124, 125] data have shown
clear benefits in terms of myocardial perfusion and survival from early abciximab administration. Recently, the
ON-TIME II trial [126] showed significant benefits from early high-dose tirofiban administration before transfer
for primary angioplasty as compared to placebo.
Initial non-randomised studies have suggested greater benefits from selective intracoronary administration.
The recently published CICERO trial [127] has shown no benefits in infarct size and clinical outcome. Similarly,
the AIDA STEMI (ST-elevation myocardial infarction) trial, including more than 2,000 patients, did not prove any
benefit in reduction of clinical endpoints relating to intracoronary over intravenous administration of abciximab.
In the recently reported INFUSE AMI (acute myocardial infarction) trial intralesional administration of abciximab
using the ClearWay™ RX infusion catheter (Atrium Medical, Hudson, NH, USA) was associated with significant,
however, modest reduction of the infarct size assessed by cardiac magnetic resonance at 30 days after first, an-
terior wall STEMI (ST-elevation myocardial infarction) in comparison to no abciximab administration. The high-
est benefit was observed when local infusion of abciximab was combined with prior thrombus aspiration [128].
Several meta-analyses [129, 130] have shown similar results between high-dose tirofiban (25 ug/kg) (5 trials), ep-
tifibatide (double-bolus) (1 trial) as compared to abciximab. However, no trial was adequately powered to evalu-
ate any difference in hard endpoints such as mortality. In the FATA trial [131], including 400 STEMI (ST-elevation
myocardial infarction) patients, Marzocchi et al failed to show non-inferiority of high-dose tirofiban as com-
pared to abciximab. The need for a second bolus (10 minutes after the first one) of eptifibatide may be less
user-friendly in the setting of primary PCI (percutaneous coronary intervention).
Current recommendations for antiplatelet drugs in patients with STEMI (ST-elevation myocardial infarction) are
shown in ! Table 3 (108_1904_table3.png) .
ANTITHROMBOTIC THERAPY BEFORE, DURING AND AFTER ANGIOPLAS-

TY
Unfractionated heparin & bivalirudin
Based on current recommendations [3], anticoagulation in patients with STEMI (ST-elevation myocardial infarc-
tion) includes unfractionated heparin (UFH) (50-60 IU/kg i.v. bolus if the usage of GP IIb–IIIa inhibitor is planned
or 70-100 IU/kg i.v. bolus without GP IIb–IIIa inhibitor), bivalirudin (0.75 mg/kg i.v. bolus followed by 1.75mg/kg/h
i.v. infusion), or enoxaparin (0.5 mg/kg i.v. followed by s.c. treatment). Importantly bivalirudin (with use of GP
IIb-IIIa inhibitor restricted to bailout) is recommended over UFH (unfractionated heparin) according to current
guidelines (I B).

Page 17 of 25
UFH can be administered before cathlab admission; however, dose of i.v. bolus dose should not exceed 5,000 IU
(international units). Before primary PCI (percutaneous coronary intervention), activated clotting time (ACT)
should be checked and additional boluses of UFH (unfractionated heparin), if required, should be given to
achieve an ACT (activated clotting time) target range between 200 and 250 seconds if GP IIb-IIIa inhibitors are
used, and ACT (activated clotting time) between 250 and 300 seconds in patients without GP IIb-IIIa inhibitors.
Monitoring of ACT (activated clotting time) and dose adjustment is not required in patients treated with bi-
valirudin, except patients with severe renal dysfunction in whom reduction of i.v. infusion dose to 1.0 mg/kg/h
should be considered [4]. Bivalirudin can also be used in patients initially treated with UFH (unfractionated he-
parin); however, bivalirudin should be administered >30 minutes from the last UFH (unfractionated heparin)
dose. There is no need for prolonged use of antithrombotic agents after successful primary PCI (percutaneous
coronary intervention) for STEMI (ST-elevation myocardial infarction), except for a few clinical indications (left
ventricle aneurysm and/or thrombus, atrial fibrillation, prolonged bed rest, deferred sheath removal, use of
IABP (intra-aortic balloon pump)).
No specific randomised clinical trial has been conducted to address the impact of UFH (unfractionated heparin)
on the safety and efficacy of primary PCI (percutaneous coronary intervention). UFH (unfractionated heparin) is
currently recommended based on the opinion of experts (I C, ! Table 3 (108_1904_table3.png) ) [3]. Recom-
mendation for the use of bivalirudin is based on the results from the randomised, open-label, multicentre HORI-
ZONS-AMI trial [132, 133]. In this study, among patients undergoing primary PCI (percutaneous coronary inter-
vention) for STEMI (ST-elevation myocardial infarction), bivalirudin monotherapy (n=1,800) was associated with a
significantly lower 30-day rate of net adverse clinical events in comparison to patients treated with a combina-
tion of UFH (unfractionated heparin) and GP IIb-IIIa inhibitors (n=1,802). The observed benefit was primarily dri-
ven by a lower risk of non-CABG major bleeding. There was no difference in 30-day major adverse CV event
rates between groups. These 30-day clinical outcomes were maintained at 3-year follow-up. Importantly, bi-
valirudin monotherapy compared to a combination of UFH (unfractionated heparin) and GP IIb-IIIa inhibitors
was associated with significant cardiac and all-cause mortality reduction during short-term (30-day), as well as
long-term (up to 3 years) follow-up. Although there was an increased risk of acute stent thrombosis (<24 hours)
in the bivalirudin group, no significant increase was present by 30 days and 3 years. Broader use of bivalirudin,
as an alternative to a combination of UFH (unfractionated heparin) and GP IIb-IIIa inhibitors, especially in pa-
tients with an increased risk of bleeding, should be recommended [3]. Also, bivalirudin is unanimously recom-
mended as a replacement for heparin in the case of heparin-induced thrombocytopenia.
Recently published results of the EUROMAX study have confirmed the safety and efficacy of bivalirudin adminis-
tration during transfer for primary PCI (percutaneous coronary intervention). In this study, 2,218 patients with
STEMI (ST-elevation myocardial infarction) were randomized to receive either bivalirudin or UFH/enoxaparin
with optional GP IIb-IIIa inhibitors (control group). Initiation of bivalirudin before transfer for primary PCI (percu-
taneous coronary intervention) was associated with reduction of non-CABG-related major bleeding as well as a
composite endpoint of death and non-CABG-related major bleeding at 30 days as compared to control group.
However, the higher risk of stent thrombosis was observed in patients treated with bivalirudin[134].
Fondaparinux
The use of fondaparinux in the setting of primary PCI (percutaneous coronary intervention) in patients with STE-
MI (ST-elevation myocardial infarction) is not currently recommended (III B) [3]. The clinical safety and efficacy of
fondaparinux has been tested in 12,092 STEMI (ST-elevation myocardial infarction) patients enrolled in the ran-
domised, double-blind, multicentre OASIS-6 trial [135]. Significant benefits of fondaparinux were observed in
patients receiving thrombolytic therapy and those not receiving any reperfusion therapy. On the other hand,
there was a trend to harm among 3,768 patients undergoing primary PCI (percutaneous coronary intervention)
in terms of death and reinfarction at 30 days, with a higher rate of guiding catheter thrombosis and more coro-
nary complications (abrupt coronary artery closure, new angiographic thrombus, catheter thrombus, no-reflow,
dissection, or perforation) with fondaparinux [135]. Fondaparinux use was associated with lower rates of major
bleeding events in all patient groups except primary PCI (percutaneous coronary intervention) patients. The ob-
served higher intracatheter thrombosis rate is explained by the fact that fondaparinux and other pentasaccha-
rides, in contrast to UFH (unfractionated heparin), are ineffective in blocking the contact activation of the coagu-

Page 18 of 25
lation pathway. The existence of such patomechanisms, as well as data from OASIS-6 and the more recent FU-
TURA-OASIS-8 study [136], support the need for full-dose UFH (unfractionated heparin) administration during
primary PCI (percutaneous coronary intervention) for STEMI (ST-elevation myocardial infarction) in patients pre-
treated with fondaparinux.
Enoxaparin
There is a growing amount of data concerning the safety and feasibility of i.v. administration of enoxaparin dur-
ing primary PCI (percutaneous coronary intervention) for STEMI (ST-elevation myocardial infarction). In the
STEEPLE study [137], enoxaparin administration at the dose of 0.5 mg/kg i.v. bolus in elective patients was asso-
ciated with significant reduction of the risk of major bleeding in comparison to UFH (unfractionated heparin).
Such clinical benefit was not confirmed for higher dose (0.75 mg/kg) of enoxaparin. In therandomised, open-la-
bel, multicentre ATOLL trial, the use of 0.5 mg/kg i.v. bolus of enoxaparin during primary PCI (percutaneous
coronary intervention) for STEMI (ST-elevation myocardial infarction) was associated with significant reduction
of the risk of composite ischaemic endpoint of death, recurrent MI and urgent revascularisation during 30-day
follow-up in comparison to UFH (unfractionated heparin). There was no difference in the non-CABG major
bleeding rate between groups. Based on results of the ATOLL study, enoxaparin (with or without routine GP IIb-
IIIa inhibitor) may be preferred over UFH (unfractionated heparin) according to ESC STEMI (ST-elevation myocar-
dial infarction) guidelines (IIb; B)[3].
Current recommendations for antithrombotic drugs in patients with STEMI (ST-elevation myocardial infarction)
are shown in ( ! Table 3 (108_1904_table3.png) ).
ROLE OF LYTICS IN STEMI (ST-ELEVATION MYOCARDIAL INFARCTION)

TREATMENT
Introduction and definitions: complementarity of the two treatment modalities
Fibrinolysis offers an opportunity for early restoration of flow in patients too far from a primary PCI (percuta-
neous coronary intervention) centre to reach it within 90-120 minutes. Fibrinolysis is not a stand-alone treat-
ment because a mechanical intervention is needed to obtain coronary reperfusion in patients with failed throm-
bolysis (rescue PCI (percutaneous coronary intervention)) and to decrease the risk of further ischaemic events in
patients with successful thrombolysis (urgent early PCI (percutaneous coronary intervention) after fibrinolysis).
In the attempt to minimise the time delay to reperfusion, the administration of fibrinolysis has been advocated
in all patients undergoing PCI (percutaneous coronary intervention) (facilitated PCI (percutaneous coronary in-
tervention)). The definition was stretched to indicate whatever concomitant, more powerful antiplatelet regimen
was added to the conventional aspirin and clopidogrel. Especially after the introduction of prasugrel and tica-
grelor, preferred in STEMI (ST-elevation myocardial infarction) because of their rapid action, and the reduced
use of GP IIb-IIIa inhibitors produced by the negative results of HORIZONS-AMI, BRAVE 3 and other trials, the ap-
proach we recommend is to stick to the more logical definition of facilitated PCI (percutaneous coronary inter-
vention), limited to fibrinolytics. Since an excess bleeding risk was consistently induced by fibrinolysis before PCI
(percutaneous coronary intervention), with no improvement in other adverse events, for patients who can re-
ceive primary PCI (percutaneous coronary intervention) promptly, fibrinolysis plays no role in optimal PCI (per-
cutaneous coronary intervention) candidates able to receive this treatment within 90-120 minutes.
Facilitated angioplasty must be distinguished by the use of fibrinolysis for those patients for whom primary PCI
(percutaneous coronary intervention) is not available within 90-120 minutes. In the past, those patients were
considered as a medically treated cohort and the indications to PCI (percutaneous coronary intervention) were
established based on clinical criteria and mainly limited to patients with evidence of residual ischaemia. This
conventional conservative approach is challenged by the fact that more than 1/3 of the patients with STEMI (ST-
elevation myocardial infarction) undergoing fibrinolysis do not show signs of reperfusion, and that, even when
reperfusion is achieved, they have a considerable risk of recurrent MI and ischaemia because of late occlusion
of the severe unstable residual stenosis which caused the initial episode. Since fibrinolysis is not an alternative
to transfer for PCI (percutaneous coronary intervention), the organisational model of a territorial network for
the treatment of STEMI (ST-elevation myocardial infarction) patients should not be limited to the areas around

Page 19 of 25
primary PCI (percutaneous coronary intervention) hospitals but should be expanded to provide a timely access
to hospitals with 24/7 interventional facilities also to patients coming from areas too far away for a timely pri-
mary PCI (percutaneous coronary intervention) treatment and who should be treated with fibrinolysis locally
and then transferred for rescue PCI (percutaneous coronary intervention) or for an urgent early invasive man-
agement.
Which fibrinolytic agent should we use?

Interventional cardiologists should be well aware of the benefit of fibrinolytic therapy because, as for multives-
sel or left main PCI (percutaneous coronary intervention) which indirectly established their prognostic benefit
versus medical treatment by being compared to bypass surgery, the evidence of superiority of primary PCI (per-
cutaneous coronary intervention) has been compared to the previous gold standard, i.e, fibrinolysis. Fibrinolysis
prevents approximately 30 early deaths per 1,000 patients treated within 6 h after symptom onset [138]. Over-
all, the largest absolute benefit is seen among patients with the highest risk, but the proportional benefit is simi-
lar. The benefit is also seen in the elderly: in a subgroup of 3,300 patients over the age of 75 presenting within
12 h of symptom onset and with either ST-segment elevation or bundle-branch block, mortality rates were sig-
nificantly reduced by fibrinolytic therapy.
Unfortunately, contraindications and especially the risk of bleeding complications are so high after 75 years that
few of these patients can benefit from the potential advantage of fibrinolytic therapy. As with and more so than
for primary PCI (percutaneous coronary intervention), time is the most crucial factor for the success of fibrinoly-
sis. While for primary PCI (percutaneous coronary intervention) a time delay only limits the ability to recover my-
ocardial function, the organisation of the occlusive coronary thrombus reduces the penetration in the thrombus
and the ability to break the links of the fibrin strands. These two reasons explain why guidelines tend to have
different time indications for fibrinolytics and primary PCI (percutaneous coronary intervention), with the first
recommended almost exclusively in the first 6 hours after symptom onset because beyond that time and cer-
tainly beyond 12 hours the limited success rate does not justify the preliminary use of fibrinolysis which will im-
prove only marginally the relative delay of primary PCI (percutaneous coronary intervention). Conversely, before
3 and especially before 1 or 2 hours from symptom onset, the greater success rate of fibrinolysis and the
greater clinical relevance of even small time delays to reperfusion in the golden hours when every minute
counts for myocardial recovery suggest a liberal use of fibrinolytics, especially in larger anterior MI and in
groups at low risk. Unlike primary PCI (percutaneous coronary intervention), fibrinolysis can be administered
before hospital admission, provided the diagnosis is firmly established and the medical/paramedical crew is cer-
tified and trained for use. A meta-analysis of studies in which >6,000 patients were randomised to pre-hospital
or in-hospital thrombolysis has shown significant reduction (17%) in early mortality with pre-hospital treatment
[139]. In a meta-analysis of 22 trials, a much larger mortality reduction was found in patients treated within the
first 2 h than in those treated later [140]. More recent post hoc analyses of several randomised trials and data
from registries have confirmed the clinical usefulness of pre-hospital fibrinolysis [35, 141, 142, 143]. Most of
these studies reported outcome data similar to those of primary PCI (percutaneous coronary intervention), pro-
vided early angiography and PCI (percutaneous coronary intervention) were performed in those who needed in-
tervention.
Fibrinolytic therapy is associated with a small but significant increase in strokes, mainly occurring on the first
day after treatment [138]. Early strokes are almost exclusively caused by cerebral haemorrhages, while later
strokes are more frequently thrombotic or embolic and can also develop after primary PCI (percutaneous coro-
nary intervention). Old age, low weight, female gender, prior cerebrovascular disease, and systolic and diastolic
hypertension on admission predict the development of intracranial haemorrhages [144]. In the latest trials, in-
tracranial bleeding occurred in 0.9%-1.0% of the total population studied [145, 146]. Major non-cerebral bleeds
(bleeding complications requiring blood transfusion or those which are life-threatening) can occur in 4%-13% of
the patients treated [145, 147]. In patients undergoing subsequent PCI (percutaneous coronary intervention),
the most common sources of bleeding are procedure-related.

Page 20 of 25
Administration of streptokinase may be associated with hypotension, but severe allergic reactions are rare.
Streptokinase should not be re-administered because of antibodies which can impair its activity and because of
the risk of allergic reactions. The advantages provided by new fibrin-specific lytics are small but well demon-
strated. In the GUSTO (global utilisation of streptokinase and tissue plasminogen act) trial, which included
>30,000 patients, an accelerated infusion of the fibrin-specific agent t-PA (tissue plasminogen activator; al-
teplase) resulted in 10 fewer deaths per 1,000 patients [148]. Double-bolus r-PA (reteplase) does not offer any
further mortality reduction over accelerated t-PA except for its ease of administration [146]. Single-bolus
weight-adjusted tenecteplase is equivalent to accelerated t-PA for 30-day mortality and is associated with a sig-
nificantly lower rate of non-cerebral bleedings and less need for blood transfusion [145]. This single-bolus
weight-adjusted drug is particularly advantageous in the pre-hospital setting and has gained popularity in most
European countries.
For patients screened in the dedicated mobile units where pre-hospital diagnosis can be established, and for
patients arriving directly to the hospital, a realistic aim is to initiate fibrinolysis within 30 minutes (door-to-nee-
dle time) with a maximum tolerated delay of 60 minutes.
Pre-hospital fibrinolysis
It is reasonable to initiate fibrinolytic therapy as fast as possible after the confirmation of STEMI (ST-elevation
myocardial infarction) diagnosis. In many networks, administration of fibrinolytic therapy in a pre-hospital set-
ting was introduced to decrease time from symptom onset to treatment. This strategy is especially feasible in
locations where fibrinolytic therapy is administered by paramedics [149] or general practitioners. In addition, it
may be a valuable option in rural or congested urban areas where transportation times are very long, as well as
in areas in which primary PCI (percutaneous coronary intervention) facilities are not immediately available. Fibri-
nolytics used as i.v. bolus should be preferred over i.v. infusion to facilitate pre-hospital management. Impor-
tantly, following pre-hospital fibrinolysis, the ambulance should transport the patient to a 24 h a day/7 days a
week primary PCI (percutaneous coronary intervention) facility.
A number of studies have demonstrated that pre-hospital fibrinolysis may allow a decrease in both time from
symptom onset to treatment [139, 149, 150] and from symptom onset to successful reperfusion [150]. More-
over, several studies have shown improved outcomes, including mortality reduction associated with pre-hospi-
tal-initiated fibrinolysis in comparison to in-hospital fibrinolysis [139, 151], as well as to primary PCI (percuta-
neous coronary intervention) [151]. In the CAPTIM study, pre-hospital fibrinolysis (with transfer to an interven-
tional facility for possible rescue PCI (percutaneous coronary intervention)) was associated with similar rates of
the composite primary endpoint (death, non-fatal reinfarction, and non-fatal disabling stroke within 30 days) or
mortality in comparison to primary PCI (percutaneous coronary intervention) [152]. However, post hoc analysis
of data from the CAPTIM study revealed that patients randomised <2 hours after symptom onset had a strong
trend towards lower 30-day mortality with pre-hospital thrombolysis compared with those randomised to pri-
mary PCI (percutaneous coronary intervention) (2.2% vs. 5.7%, p=0.058), whereas mortality was similar in pa-
tients randomised ≥2 hours [141]. After 5 years of follow-up, the difference in mortality in patients randomised
within 2 hours reached statistical significance (5.8% vs. 11.1%, respectively, p=0.04) [153]. The advantage of pre-
hospital fibrinolysis over primary PCI (percutaneous coronary intervention) in terms of reduction of 1-year mor-
tality in early presenters (patients randomised within 2 hours from symptom onset) was also confirmed by com-
bined analysis of data from CAPTIM and WEST studies (2.8% vs. 6.9%, respectively, p=0.021) [154]. However,
whether pre-hospital fibrinolysis is associated with a similar or better clinical outcome than primary PCI (percu-
taneous coronary intervention) in patients presenting early has not been studied prospectively in an adequately
sized randomised fashion. The STREAM study comparing primary PCI (percutaneous coronary intervention)
against an active rescue strategy did not show a difference in mortality between both strategies [30, 155].
Treatment after fibrinolysis

In cases of failure of a fibrinolytic treatment re-administration of a second dose of fibrinolysis was not shown to
be beneficial [46] and patients should be immediately transferred for rescue angioplasty based on data present-
ed above. .The approach for patients in whom it is likely that fibrinolysis was successful (>50% ST-segment reso-
lution at 60-90 minutes, typical reperfusion arrhythmia, disappearance of chest pain) is more controversial. A

Page 21 of 25
strategy of routine early angiography is recommended if there are no contraindications [3, 4]. Various ran-
domised trials [38, 39, 41] and two contemporary meta-analyses [43, 156] have shown that early routine post-
thrombolysis angiography with subsequent PCI (percutaneous coronary intervention) if required (“drip & ship”)
reduces the rates of reinfarction and recurrent ischaemia both at 30 days and 1 year compared with a conven-
tional “watch & wait” strategy with angiography and revascularisation only in patients with spontaneous or in-
duced severe ischaemia or left ventricular dysfunction.
NO-REFLOW TREATMENT IN THE STEMI (ST-ELEVATION MYOCARDIAL IN-

FARCTION) SETTING
Principles of no-reflow prevention and treatment are described in Chapter 3.24. In the case of no-reflow phe-
nomenon occurrence during primary PCI (percutaneous coronary intervention), intracoronary administration of
adenosine and verapamil could be useful. The direct nitric oxide donor sodium nitroprusside (used as repeated
intracoronary boluses of 50-100 μg, up to 1,000 μg under blood pressure control) seems to be the most effec-
tive in improvement of microcirculatory flow. In some cases, 2 or 3 of these drugs may be combined. In cases of
pharmacotherapy resistant no-reflow phenomenon, the use of IABP (intra-aortic balloon pump) may be justi-
fied.
Angiographic methods of reperfusion assessment

Immediate results of reperfusion with primary PCI (percutaneous coronary intervention) may be analysed at
epicardial and myocardial level. In daily clinical practice, epicardial flow is assessed according to 4 grades - quali-
tative TIMI (thrombolysis in myocardial infarction) flow grade scale (Chapter 2.06). The scale describes the pres-
ence and speed of epicardial vessel filling with contrast [157]. Another tool, used more for research, is the TIMI
(thrombolysis in myocardial infarction) frame count (TFC), which is quantitative flow assessment, so it is less
subjective than the TIMI (thrombolysis in myocardial infarction) flow grade [158]. TFC is based on the calculation
of the number of cine frames required for contrast first to reach standardised distal coronary landmarks in the
infarct-related artery (Chapter 2.06). Another two scales were proposed for assessment of reperfusion based on
myocardial level. The TIMI (thrombolysis in myocardial infarction) myocardial perfusion grade scale (TMPG) was
described by the TIMI (thrombolysis in myocardial infarction) group based on studies of fibrinolysis treatment
[159]. In the TMPG scale, the filling and clearance of contrast in the myocardium is analysed distal to the culprit
lesion. The myocardial blush grade (MBG) scale was proposed by the Zwolle group based on primary PCI (percu-
taneous coronary intervention) studies [160]. MBG (myocardial blush grade) assessment is based on analysis of
contrast density in the microcirculation (Chapter 2.06). All of the above-mentioned angiographic scales correlate
well with patient clinical outcome, including mortality.
Electrocardiographic methods of reperfusion assessment - ST-segment resolution

ST-segment assessment after reperfusion therapy is a commonly used parameter which correlates well with
clinical outcome including long-term mortality. Electrocardiographic (ECG) ST-segment changes reflect myocar-
dial rather than epicardial flow. This provides complementary information beyond the angiographic parameters.
ECG (electrocardiogram) ST-segment resolution (STR) analysis is one of the most popular methods of reperfu-
sion assessment and it is widely used in clinical practice [161]. There are at least three methods of ST-segment
analysis. The most popular is the resolution of the sum of ST-segment elevation in ECG (electrocardiogram) at a
given time point after primary PCI (percutaneous coronary intervention) compared to baseline ECG (electrocar-
diogram) [162]. Two others are single-lead STR and maximum ST-segment elevation after primary PCI (percuta-
neous coronary intervention) [163, 164]. These last two methods are simpler but both have good predictive ac-
curacy, even better than the sum STR model. In the study of Brodie et al, STR and maximum ST-segment eleva-
tion after PCI (percutaneous coronary intervention) were analysed in more than 1,000 patients showing good
correlation with clinical outcome [165]. Similarly, analysis of the CADILLAC population confirmed the value of
these parameters as predictors of outcome [166]. In both studies, the time window for ECG (electrocardiogram)
after PCI (percutaneous coronary intervention) was liberal and defined as less than 4 hours. In the APEX-AMI
ECG (electrocardiogram) analysis, ST-segment parameters were assessed based on ECG (electrocardiogram) per-
formed early (30 minutes) after PCI (percutaneous coronary intervention). All correlated well with 90-day clinical

Page 22 of 25
events (death, shock, heart failure) [167]. In studies of thrombolytic therapy, ECG (electrocardiogram) parame-
ters were analysed in a predefined time window which was driven by the pharmacokinetics of a certain agent.
However, in clinical practice early reperfusion assessment after thrombolysis is very important because it facili-
tates decision-making about the potential use of rescue PCI (percutaneous coronary intervention) treatment
(see Rescue PCI (percutaneous coronary intervention)).
CONCLUSION
Primary PCI (percutaneous coronary intervention) is a preferred method of reperfusion in patients with STEMI
(ST-elevation myocardial infarction). To overcome reperfusion delay caused by logistical problems, regional net-
works should be introduced based on cooperation of primary PCI (percutaneous coronary intervention) centres
with ambulances and non-PCI-capable hospitals. When the anticipated delay to primary PCI (percutaneous
coronary intervention) is longer than recommended, pre-hospital or in-hospital fibrinolytic therapy should be
administered as soon as possible, as a bridge to invasive treatment. PCIs for STEMI (ST-elevation myocardial in-
farction) carry a higher risk of complications including distal embolisation or no-reflow which influence clinical
outcome. Modern pharmacotherapy, aspiration thrombectomy, and new stent designs allow a reduction in the
risk of such complications and an improvement in immediate and long-term results of primary PCI (percuta-
neous coronary intervention).
PERSONAL PERSPECTIVE – DARIUSZ DUDEK

Due to rapid evolution in the invasive treatment of acute MI, such an approach became a separate part of
interventional cardiology. Currently, management of patients with STEMI (ST-elevation myocardial infarction)
is not only a mechanical restoration of the flow within the infarct-related artery, but it also includes a system
of early diagnosis and rapid transfer to PCI-capable centres, selection of optimal adjunctive pharmacothera-
py and finally PCI (percutaneous coronary intervention) procedure with dedicated devices. All these compo-
nents are necessary for the eventual success of the treatment. The networking concept which was intro-
duced to overcome the time delay from the first medical contact to the primary PCI (percutaneous coronary
intervention) centre is currently accepted as an optimal model of STEMI (ST-elevation myocardial infarction)
treatment organisation. Well established cooperation of a primary PCI (percutaneous coronary intervention)
centre, non-PCI hospitals and emergency medical systems is crucial for rapid diagnosis and transfer. The
second key component of optimal treatment of STEMI (ST-elevation myocardial infarction) is selection of ad-
junctive pharmacotherapy, especially antiplatelet and antithrombotic agents. New drugs allow a reduction in
rates of clinical events including mortality, but this benefit may be reduced by the higher risk of bleedings in
some patients. That is why adjunctive pharmacotherapy should be tailored to the individual patient, based
on assessment of ischaemic and bleeding risk. Such an approach consists not only of deciding on optimal
agent choice, but also on the moment (before transfer, in the cathlab before angiography, or in the cathlab
after angiography/PCI) and the means of administration (intravenous, intracoronary or intralesion adminis-
tration), and its application is only possible when performed by experienced medical staff. New technologies
such as aspiration thrombectomy, new stent designs (mesh-covered stents, self-expandable stents)and local
drug delivery systems are more and more frequently used during primary PCI (percutaneous coronary inter-
vention), but not for elective procedures. Therefore, operator experience is fundamental for procedural suc-
cess. All these factors make the primary PCI (percutaneous coronary intervention) approach different from a
planned intervention. That is why interventional STEMI (ST-elevation myocardial infarction) treatment should
be performed in experienced, well equipped centres working in a network system and providing 24/7 prima-
ry PCI (percutaneous coronary intervention) programmes.

Page 23 of 25
STEMI GUIDELINES 2012
http://www.escardio.org/GUIDELINES-SURVEYS/ESC-GUIDELINES/Pages/acs-st-segment-elevation.aspx
(http://www.escardio.org/GUIDELINES-SURVEYS/ESC-GUIDELINES/Pages/acs-st-segment-elevation.aspx)
! REFERENCES
RECOMMENDED REFERENCES
1. Widimsky P, Wijns W, Fajadet J, de Belder M, Knot J, Aaberge L, Andrikopoulos G, Baz JA, Betriu A, Claeys M,
Danchin N, Djambazov S, Erne P, Hartikainen J, Huber K, Kala P, Klinceva M, Kristensen SD, Ludman P, Ferre JM,
Merkely B, Milicic D, Morais J, Noc M, Opolski G, Ostojic M, Radovanovic D, De Servi S, Stenestrand U, Studen-
can M, Tubaro M, Vasiljevic Z, Weidinger F, Witkowski A, Zeymer U. Reperfusion therapy for ST elevation acute
myocardial infarction in Europe: description of the current situation in 30 countries. Eur Heart J. 2010;31:943-
957. # (http://www.ncbi.nlm.nih.gov/pubmed?term=Eur Heart J. 2010;31:943-957.)
4. Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, Garg S, Huber K, James S, Knuuti J, Lopez-Sendon J,
Marco J, Menicanti L, Ostojic M, Piepoli MF, Pirlet C, Pomar JL, Reifart N, Ribichini FL, Schalij MJ, Sergeant P, Ser-
ruys PW, Silber S, Sousa UM, Taggart D, Vahanian A, Auricchio A, Bax J, Ceconi C, Dean V, Filippatos G, Funck-
Brentano C, Hobbs R, Kearney P, McDonagh T, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Vardas
PE, Widimsky P, Kolh P, Alfieri O, Dunning J, Elia S, Kappetein P, Lockowandt U, Sarris G, Vouhe P, Kearney P, von
Segesser L, Agewall S, Aladashvili A, Alexopoulos D, Antunes MJ, Atalar E, Brutel de la Riviere A, Doganov A, Eha
J, Fajadet J, Ferreira R, Garot J, Halcox J, Hasin Y, Janssens S, Kervinen K, Laufer G, Legrand V, Nashef SA, Neu-
mann FJ, Niemela K, Nihoyannopoulos P, Noc M, Piek JJ, Pirk J, Rozenman Y, Sabate M, Starc R, Thielmann M,
Wheatley DJ, Windecker S, Zembala M. Guidelines on myocardial revascularization: The Task Force on Myocar-
dial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-
Thoracic Surgery (EACTS). Eur Heart J. 2010;31:2501-2555 (tel:2501-2555). # (http://www.ncbi.nlm.nih.-
gov/pubmed?term=Eur Heart J. 2010;31:2501-2555.)
8. Knot J, Widimsky P, Wijns W, Stenestrand U, Kristensen SD, van’t Hof AW, Weidinger F, Janzon M, Norgaard
BL, Soerensen JT, van de Wetering H, Thygesen K, Bergsten PA, Digerfeldt C, Potgieter A, Tomer N, Fajadet J.
How to set up an effective national primary angioplasty network: lessons learned from five European coun-
tries. EuroIntervention. 2009;5:299-309. # (http://www.ncbi.nlm.nih.gov/pubmed?term=EuroIntervention.
2009;5:299-309.)
29. Boersma E. Does time matter? A pooled analysis of randomized clinical trials comparing primary percuta-
neous coronary intervention and in-hospital fibrinolysis in acute myocardial infarction patients. Eur Heart J.
2006;27:779-788. # (http://www.ncbi.nlm.nih.gov/pubmed?term=Eur Heart J. 2006;27:779-788.)
37. Fernandez-Aviles F, Alonso JJ, Castro-Beiras A, Vazquez N, Blanco J, onso-Briales J, Lopez-Mesa J, Fernandez-
Vazquez F, Calvo I, Martinez-Elbal L, San Roman JA, Ramos B. Routine invasive strategy within 24 hours of
thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment
elevation (GRACIA-1): a randomised controlled trial. Lancet. 2004;364:1045-1053. # (http://www.ncbi.nlm.nih.-
gov/pubmed?term=Lancet. 2004;364:1045-1053.)
66. Hannan EL, Samadashvili Z, Walford G, Holmes DR, Jr., Jacobs AK, Stamato NJ, Venditti FJ, Sharma S, King
SB, III. Culprit vessel percutaneous coronary intervention versus multivessel and staged percutaneous coro-
nary intervention for ST-segment elevation myocardial infarction patients with multivessel disease. JACC Car-
diovasc Interv. 2010;3:22-31. # (http://www.ncbi.nlm.nih.gov/pubmed?term=JACC Cardiovasc Interv.
2010;3:22-31.)
113. Steg PG, James S, Harrington RA, Ardissino D, Becker RC, Cannon CP, Emanuelsson H, Finkelstein A,
Husted S, Katus H, Kilhamn J, Olofsson S, Storey RF, Weaver WD, Wallentin L. Ticagrelor versus clopidogrel in

Page 24 of 25
patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous
coronary intervention: A Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation.
2010;122:2131-2141 (tel:2131-2141). # (http://www.ncbi.nlm.nih.gov/pubmed?term=Circulation.
2010;122:2131-2141.)
122. Ellis SG, Tendera M, de Belder MA, van Boven A J, Widimsky P, Janssens L, Andersen HR, Betriu A, Savonitto
S, Adamus J, Peruga JZ, Kosmider M, Katz O, Neunteufl T, Jorgova J, Dorobantu M, Grinfeld L, Armstrong P,
Brodie BR, Herrmann HC, Montalescot G, Neumann FJ, Effron MB, Barnathan ES, Topol EJ. Facilitated PCI in pa-
tients with ST-elevation myocardial infarction. N Engl J Med. 2008;358:2205-2217 (tel:2205-2217). #
(http://www.ncbi.nlm.nih.gov/pubmed?term=N Engl J Med. 2008;358:2205-2217.)
139. Morrison LJ, Verbeek PR, McDonald AC, Sawadsky BV, Cook DJ. Mortality and prehospital thrombolysis for
acute myocardial infarction: A meta-analysis. JAMA. 2000;283:2686-2692 (tel:2686-2692). #
(http://www.ncbi.nlm.nih.gov/pubmed?term=JAMA. 2000;283:2686-2692.)
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PART III CHAPTER 17 (http://www.stentforlife.com/)

INTERVENTIONS FOR ST-SEGMENT ELEVA-

CHAPTER UNDER UPDATE

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NETWORKING OF ACUTE MYOCARDIAL INFARCTION TREATMENT

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TIME DELAYS IN MYOCARDIAL INFARCTION

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IMPORTANCE OF DELAY TO MECHANICAL REPERFUSION

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TIMING OF ANGIOGRAPHY AND PCI (PERCUTANEOUS CORONARY INTER-

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" FOCUS BOX 1

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ACCESS SITE SELECTION

CATHETER AND GUIDEWIRE SELECTION

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PRIMARY PCI (PERCUTANEOUS CORONARY INTERVENTION) STRATEGY

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THROMBECTOMY, PROXIMAL AND DISTAL PROTECTION

Distal protection devices

A) Distal occlusive devices

Proximal protection devices

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STENT SELECTION (BARE METAL, DRUG-ELUTING, MESH-COVERED

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Forecast the compliance to long-term dual antiplatelet therapy.

IABP & LEFT VENTRICULAR ASSIST DEVICES

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ANTIPLATELET THERAPY BEFORE, DURING AND AFTER ANGIOPLASTY

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Prasugrel vs. ticagrelor

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Glycoprotein IIb-IIIa inhibitors

ANTITHROMBOTIC THERAPY BEFORE, DURING AND AFTER ANGIOPLAS-

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ROLE OF LYTICS IN STEMI (ST-ELEVATION MYOCARDIAL INFARCTION)

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Which ﬁbrinolytic agent should we use?

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Treatment after ﬁbrinolysis

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NO-REFLOW TREATMENT IN THE STEMI (ST-ELEVATION MYOCARDIAL IN-

Angiographic methods of reperfusion assessment

Electrocardiographic methods of reperfusion assessment - ST-segment resolution

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PERSONAL PERSPECTIVE – DARIUSZ DUDEK

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