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Saudi Clinical Practice Guideline on Management of ST-elevation myocardial infarction

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i
Management of STEMI
Guideline Panel Members
Saudi Expert Panel
Dr. Adel Tash
Dr. Hamed Alghamdi
Dr. Faisal Al Samadi
Dr. Zohair Al Aseri
Dr. Owayed Al Shammeri
Dr. Amr Bannan
Mr. Mohammed Al Otaibi (Patient Representative)
McMaster University Working Group
Veena Manja, MD MSc, Wojtek Wiercioch, MSc, Romina Brignardello Petersen, DDM, Jan
Brozek, MD PhD, and Holger Schünemann, MD PhD, on behalf of the McMaster Guideline
Working Group
Acknowledgements
We acknowledge Dr Waqar Ahmed, Dr Mirvat Alasnag, Dr Khalid Al Faraidy, Dr Hind Al-
modaimegh, Dr Fawaz Almutairi, Prof. Ahmad Hersi, Dr Tarek Kashour, and Dr Eman Younis
for their contribution to this work.
We gratefully acknowledge Dr Ghada Bawazeer from King Saud University for
peer reviewing this final report.
Disclosure of potential conflict of interest:
All co-authors have no conflict of interest to declare.
Funding:
This clinical practice guideline was funded by the Ministry of Health, Saudi Arabia.
Address for correspondence:
Saudi Center for Evidence Based Health Care
E-mail: ebhc@moh.gov.sa
Web: http://www.moh.gov.sa/endepts/Proofs/Pages/home.aspx
ii
Management of STEMI
Abbreviations
CAD Coronary artery disease
CPG Clinical practice guideline
DM Diabetes mellitus
DTB Door to balloon time
DTN Door to needle time
EMS Emergency medical services
fPPCI Facilitated primary percutaneous coronary intervention
GRADE Grading of Recommendations, Assessment, Development and Evaluation
IHD Ischemic heart disease
KSA Kingdom of Saudi Arabia
NICE National Institute for Health and Care Excellence
QALY Quality adjusted life year
RCT Randomized controlled trial
ROSC Return of spontaneous circulation
RR Relative risk
STEMI ST-elevation myocardial infarction
tPA Tissue plasminogen activator
TNKase Tenecteplase
PCI Percutaneous coronary intervention
PPCI Primary percutaneous coronary intervention
US Unstable angina
WHO World Health Organization
iii
Management of STEMI
Contents
The Saudi Center for Evidence Based Health Care (EBHC) ..................................................................... v
Executive Summary ................................................................................................................................. 1
Introduction ........................................................................................................................................ 1
Methodology ....................................................................................................................................... 1
How to use these guidelines ............................................................................................................... 2
Key questions ...................................................................................................................................... 2
Recommendations .............................................................................................................................. 3
Scope and purpose.................................................................................................................................. 5
Introduction ............................................................................................................................................ 5
Methodology ........................................................................................................................................... 5
How to use these guidelines ................................................................................................................... 7
Key questions .......................................................................................................................................... 7
Recommendations .................................................................................................................................. 7
Question 1: Should fibrinolysis vs. delayed percutaneous coronary intervention (PPCI) be used for
treatment of STEMI in patients who present within 12 hours of symptom onset to hospitals not
capable of PPCI services? .................................................................................................................... 8
Question 2: Should facilitated percutaneous coronary intervention (fPPCI) versus percutaneous
coronary intervention (PPCI) be used in patients with STEMI? ........................................................ 10
Question 3: Should routine thrombus extraction devices during percutaneous coronary
intervention (PPCI) versus percutaneous coronary intervention (PPCI) alone be used for treatment
of STEMI? .......................................................................................................................................... 12
Question 4: Should multi-vessel PPCI versus culprit only PPCI be used in patients with STEMI and
multi-vessel coronary artery disease undergoing PPCI? ................................................................... 14
Question 5: Should early revascularization versus medical stabilization be used in patients with
cardiogenic shock due to STEMI? ..................................................................................................... 16
Question 6: Should immediate angiography followed by PPCI where indicated be used in patients
with presumed STEMI who are resuscitated but remain unconscious after a cardiac arrest? ........ 17
Question 7: Should high volume centres versus low volume centres be used for PPCI services? ... 19
Question 8: Should rescue PCI, repeat fibrinolysis, or conservative management be used in
patients with STEMI who fail to reperfuse after fibrinolytic therapy? ............................................. 20
Question 9: Should routine early angiography versus routine deferred or selective angiography be
used for STEMI successfully treated by fibrinolysis? ........................................................................ 23
References ............................................................................................................................................ 26
Appendices ............................................................................................................................................ 34
Appendix 1: Evidence to Decision Frameworks ................................................................................ 35
Guideline Question 1: Should fibrinolysis vs. delayed percutaneous coronary intervention (PPCI)
be used for treatment of STEMI in patients who present within 12 hours of symptom onset to
hospitals not capable of PPCI services? ........................................................................................ 35
Guideline Question 2: Should facilitated percutaneous coronary intervention (fPPCI) versus
percutaneous coronary intervention (PPCI) be used in patients with STEMI? ............................. 43
iv
Management of STEMI
Guideline Question 3: Should routine thrombus extraction devices during percutaneous
coronary intervention (PPCI) versus percutaneous coronary intervention (PPCI) alone be used
for treatment of STEMI? ............................................................................................................... 51
Guideline Question 4: Should multi-vessel PPCI versus culprit only PPCI be used in patients with
STEMI and multi-vessel coronary artery disease undergoing PPCI? ............................................. 62
Guideline Question 5: Should early revascularization versus medical stabilization be used in
patients with cardiogenic shock due to STEMI? ........................................................................... 68
Guideline Question 6: Should immediate angiography followed by PPCI where indicated be used
in patients with presumed STEMI who are resuscitated but remain unconscious after a cardiac
arrest? ........................................................................................................................................... 76
Guideline Question 7: Should high volume centres versus low volume centres be used for PPCI
services? ........................................................................................................................................ 84
Guideline Question 8: Should rescue PCI, repeat fibrinolysis, or conservative management be
used in patients with STEMI who fail to reperfuse after fibrinolytic therapy? ............................ 91
Guideline Question 9: Should routine early angiography versus routine deferred or selective
angiography be used for STEMI successfully treated by fibrinolysis? ........................................ 113
Appendix 2: Search Strategies and Results ..................................................................................... 121
Appendix 3: Forest Plots ................................................................................................................. 180
v
Management of STEMI
The Saudi Center for Evidence Based Health Care (EBHC)
The Saudi Centre for Evidence Based Health Care has managed and supported the coordination of
the process of clinical practice guideline (CPG) development between the methodological team from
McMaster University and the local clinical expert panel members in Saudi Arabia.
The EBHC staff members recruited local clinical experts through contacting Saudi specialist societies
and also independent experts interested in developing reliable and most up-to-date CPGs to harmo-
nize the treatment and provide the highest quality of health care in the kingdom of Saudi Arabia.
These experts were health care professionals of multidisciplinary backgrounds. As much as possible,
patient’s representatives were also included in panels.
In an effort to make national recommendations, the participating experts were professionals from
the Ministry of Health (MoH), National Guard Hospitals, King Faisal Specialist Hospital and Research
Centre (KFSHRC), University Hospitals, Security Forces Hospitals, Prince Sultan Military Medical City
(PSMMC) and from some private hospitals.
Based on a preselection of available evidence syntheses, the EBHC provided a list of potential topics
to be addressed in CPGs after thorough consultations with the local stakeholders. These topics were
further discussed with the McMaster team for important selection criteria and agreed on 12 topics
for wave 2.
The guideline panel meetings were held in Riyadh on 15th-18th March 2015 where 96 local experts
working in Saudi Arabia participated with the methodological support from 20 experts from McMas-
ter University and its partners from the American University of Beirut, Lebanon, and the University
of Freiburg, Germany, in providing high quality recommendations for common and important clinical
conditions in the Kingdom.
The Saudi Centre for EBHC supports the efforts for dissemination of the CPGs by publishing online
the full reports of the CPGs, facilitates writing concise versions of the CPGs for publication in peer
reviewed medical journals, sending hard copies to hospitals and health care centers.
Finally, a mobile App has been introduced in KSA to facilitate the dissemination efforts of the com-
pleted practice guidelines.
The staff members at the Saudi Centre for EBHC:
Dr Zulfa Al Rayess, Consultant Family Medicine, Head of Saudi Center for EBHC
Dr Yaser Adi, Scientific Advisor for the Saudi Centre for EBHC
Miss Nourah Al Moufarreh, Project Manager, Saudi Center for EBHC
1
Management of STEMI
Executive Summary
Introduction
Ischemic heart disease (IHD) is the leading
cause of morbidity and mortality around the
world and its prevalence is expected to con-
tinue to increase in developing countries.1
This is as a consequence of increasing preva-
lence of coronary artery disease (CAD) risk
factors including hypertension, diabetes melli-
tus, dyslipidemia, obesity and smoking.2 Acute
presentations of IHD (Acute Coronary Syn-
drome ACS) include ST elevation myocardial
infarction (STEMI), non-ST elevation myocar-
dial infarctions (NSTEMI) and unstable angina
(US). STEMI is a clinical syndrome character-
ized by symptoms of myocardial ischemia in
association with persistent ST segment eleva-
tion on the electrocardiogram (ECG), and sub-
sequent release of biomarkers of cardiac ne-
crosis.
The SPACE registry, a prospective registry of
ACS in 17 hospitals in the Kingdom of Saudi
Arabia (KSA), reported STEMI presentation in
41.5% of patients presenting with ACS.3 Data
from the registry suggest there is a high
prevalence of CAD risk factors in the Saudi
population including 58% of patients with di-
abetes mellitus (DM), the highest ever report-
ed rate in an ACS population. Patients pre-
senting with ACS were younger (mean age 58
years) compared with other populations.
Among patients presenting with STEMI, only
14.8% received timely administration of
thrombolytics (within 30 minutes of presenta-
tion) and 17.5% of patients received primary
percutaneous coronary intervention (PPCI).
Given the importance of this topic, the Minis-
try of Health of the Kingdom of Saudi Arabia
with the support of the McMaster University
working group produced practice guidelines
to assist health care providers in evidence-
based decision-making on the management of
ST-segment elevation myocardial infarction.
Methodology
This practice guideline is a part of the larger
initiative of the Ministry of Health of the King-
dom of Saudi Arabia to establish a program of
rigorous development of guidelines. The ulti-
mate goals are to provide guidance for clini-
cians and other healthcare decision makers
and reduce unnecessary variability in clinical
practice across the Kingdom.
The Saudi expert guideline panel selected the
topic of this guideline and all healthcare ques-
tions addressed herein using a formal prioriti-
zation process. For all selected questions we
updated existing systematic reviews on myo-
cardial infarction with ST-segment elevation
published in July 2013 by the National Clinical
Guideline Centre for the National Institute for
Health and Care Excellence (NICE).4 We also
conducted systematic searches for infor-
mation that was required to develop full
guidelines for the KSA, including searches for
information about patients’ values and pref-
erences, and costs and resource use specific
to the Saudi context. Based on the systematic
reviews we prepared summaries of available
evidence supporting each recommendation
following the GRADE (Grading of Recommen-
dations, Assessment, Development and Evalu-
ation) approach.5 We used this information to
prepare GRADE evidence-to-decision frame-
works that served the guideline panel to fol-
low the structured consensus process and
transparently document all decisions made
during the meeting (see Appendix 1). The
guideline panel met in Riyadh on March 15 &
16, 2015 and formulated all recommendations
during this meeting. Potential conflicts of in-
terests of all panel members were managed
according to the World Health Organization
(WHO) rules.6
As a quality measure for any practice guide-
line prior to publication, the final report have
been externally peer reviewed by a methodo-
logical expert who has not been involved in
this guideline development.
2
Management of STEMI
How to use these guidelines
The guideline working group developed and
graded the recommendations and assessed
the quality of the supporting evidence accord-
ing to the GRADE approach.7 Quality of evi-
dence (confidence in the estimates of effects)
is categorized as: high, moderate, low, or very
low based on consideration of risk of bias,
indirectness, inconsistency, imprecision, and
publication bias of the estimates as well as
factors that lead to upgrading the quality of
the evidence. High quality evidence indicates
that we are very confident that the true effect
lies close to that of the estimate of the effect.
Moderate quality evidence indicates moder-
ate confidence, and that the true effect is like-
ly close to the estimate of the effect, but
there is a possibility that it is substantially dif-
ferent. Low quality evidence indicates that
our confidence in the effect estimate is lim-
ited, and that the true effect may be substan-
tially different. Finally, very low quality evi-
dence indicates that the estimate of effect of
interventions is very uncertain, the true effect
is likely to be substantially different from the
effect estimate and further research is likely
to have important potential for reducing the
uncertainty.
The strength of recommendations is ex-
pressed as either strong (‘guideline panel rec-
ommends…’) or conditional (‘guideline panel
suggests…’) and has explicit implications (see
Table 1).8 Understanding the interpretation of
these two grades is essential for sagacious
clinical decision making.
Table 1: Interpretation of strong and conditional (weak) recommendations
Implications
Strong recommendation
Conditional (weak) recommendation
For patients
Most individuals in this situation
would want the recommended
course of action and only a small
proportion would not. Formal deci-
sion aids are not likely to be needed
to help individuals make decisions
consistent with their values and pref-
erences.
The majority of individuals in this situa-
tion would want the suggested course
of action, but many would not.
For clinicians
Most individuals should receive the
intervention. Adherence to this rec-
ommendation according to the
guideline could be used as a quality
criterion or performance indicator.
Recognize that different choices will be
appropriate for individual patients and
that you must help each patient arrive
at a management decision consistent
with his or her values and preferences.
Decision aids may be useful helping
individuals making decisions consistent
with their values and preferences.
For policy makers
The recommendation can be adapted
as policy in most situations
Policy making will require substantial
debate and involvement of various
stakeholders.
Key questions
1. Should fibrinolysis vs. delayed primary
percutaneous coronary intervention
(PPCI) be used for treatment of STEMI
in patients who present within 12
hours of symptom onset to hospitals
not capable of PPCI services?
2. Should facilitated primary percutane-
ous coronary intervention (fPPCI) ver-
3
Management of STEMI
sus PPCI alone be used in patients
with STEMI?
3. Should routine thrombus extraction
devices during PPCI versus PPCI alone
be used for treatment of STEMI?
4. Should multi-vessel PPCI versus culprit
only PPCI be used in patients with
STEMI and multi-vessel coronary ar-
tery disease undergoing PPCI?
5. Should early revascularization versus
medical stabilization be used in pa-
tients with cardiogenic shock due to
STEMI?
6. Should immediate angiography fol-
lowed by PPCI where indicated be
used in patients with presumed STEMI
who are resuscitated but remain un-
conscious after a cardiac arrest?
7. Should high volume centres versus
low volume centres be used for PPCI
services?
8. Should rescue PCI, repeat fibrinolysis,
or conservative management be used
in patients with STEMI who fail to
reperfuse after fibrinolytic therapy?
9. Should routine early angiography ver-
sus routine deferred or selective an-
giography be used for STEMI success-
fully treated by fibrinolysis?
Recommendations
Recommendation 1:
The panel suggests using fibrinolytic therapy
over delayed PPCI if there is a total time de-
lay >120 minutes. (conditional recommenda-
tion, very low quality evidence)
Remarks:
The total time delay of 120 minutes
refers to the period from the first con-
tact with the patient to the provision
of PPCI.
For patients presenting directly to a
PCI-capable facility the suggested ac-
ceptable time delay to provision of
PPCI is 90 minutes (i.e. door-to-
balloon time).
Recommendation 2:
The panel suggests against using fPPCI in pa-
tients with STEMI. (conditional recommenda-
tion, very low quality evidence)
Remarks:
Facilitated PPCI (fPPCI) should not be
confused with a pharmacoinvasive
PPCI strategy
Recommendation 3:
The panel recommends against routine use
of aspiration or thrombus extraction devices
in patients with STEMI. (strong recommenda-
tion, moderate quality evidence)
Recommendation 4:
The panel suggests multi-vessel PPCI over
culprit-only PCI for patients with multi-vessel
coronary artery disease undergoing PPCI.
(conditional recommendation, low quality
evidence)
Remarks:
This recommendation is based on evi-
dence with data predominantly from
patients undergoing multi-vessel PCI
during the index procedure, but the
procedure may also be considered
during the index hospitalization.
This recommendation does not apply
to patients with cardiogenic shock.
Recommendation 5:
The panel recommends early revasculariza-
tion for patients with cardiogenic shock due
to STEMI. (strong recommendation, moderate
quality evidence)
Recommendation 6:
The panel suggests immediate angiography
followed by PCI where indicated over usual
care in patients with presumed STEMI who
are resuscitated but remain unconscious af-
ter a cardiac arrest. (conditional recommen-
dation, very low quality evidence)
4
Management of STEMI
Remarks:
For patients with unwitnessed out of
hospital arrest, without documented
time of arrest, the clinician may re-
evaluate the patient for PCI with de-
tailed assessment of the patient’s
neurological status before proceeding
with a potentially futile intervention.
Recommendation 7:
The panel suggests prioritizing the manage-
ment of patients with STEMI to high volume
centres. (conditional recommendation, very
low quality evidence)
Remarks:
The implementation of this recom-
mendation should not restrict care for
patients who require PPCI in settings
where only low-volume centres are
available.
Recommendations 8, 9 and 10:
The panel suggests rescue PCI over conserva-
tive management (conditional recommenda-
tion, low quality evidence) and suggests res-
cue PCI over repeated fibrinolysis (condition-
al recommendation, low quality evidence) in
patients with STEMI who failed to reperfuse
after fibrinolytic therapy. The panel suggests
not offering repeated fibrinolysis in patients
with STEMI who fail to reperfuse after fibri-
nolytic therapy (conditional recommendation,
low quality evidence).
Remarks:
When there is no available immediate
urgent access for the patient at a
catheterization lab for the rescue PCI
procedure, treating clinicians should
determine with a lab if access to res-
cue PCI can become available for such
patients.
There should not be a repeated ad-
ministration of streptokinase. The risk
of adverse events with repeat admin-
istration of streptokinase is higher
than the benefit.
Recommendation 11:
The panel suggests routine early angiography
over routine deferred or selective angi-
ography in patients with STEMI successfully
treated by fibrinolysis. (conditional recom-
mendation, moderate quality evidence)
5
Management of STEMI
Scope and purpose
The purpose of this document is to provide
guidance about the management of ST-
segment elevation myocardial infarction. The
target audience of these guidelines includes
primary care providers, cardiologists, inter-
ventional cardiologists, emergency medicine
physicians, intensivists, hospital pharmacists,
emergency medical services and paramedics,
as well as policy makers in the Kingdom of
Saudi Arabia (KSA). Other health care profes-
sionals may also benefit from these guide-
lines.
Given the importance of this topic, the Minis-
try of Health (MoH) of Saudi Arabia with the
support of the McMaster University working
group produced practice guidelines to assist
health care providers in evidence-based deci-
sion-making. This practice guideline is a part
of the larger initiative of the Ministry of
Health of Saudi Arabia to establish a program
of rigorous adaptation and de novo develop-
ment of guidelines in the Kingdom; the ulti-
mate goal being to provide guidance for clini-
cians and other healthcare decision makers
and reduce unnecessary variability in clinical
practice across the Kingdom.
Introduction
Ischemic heart disease (IHD) is the leading
cause of morbidity and mortality worldwide
and its prevalence is expected to increase in
developing countries.1 This is as a conse-
quence of increasing prevalence of coronary
artery disease (CAD) risk factors including hy-
pertension, diabetes mellitus, dyslipidemia,
obesity and smoking.2 Acute presentations of
IHD (Acute Coronary Syndrome ACS) include
ST elevation myocardial infarction (STEMI),
non-ST elevation myocardial infarctions
(NSTEMI) and unstable angina (US). STEMI is a
clinical syndrome characterised by symptoms
of myocardial ischemia in association with
persistent ST segment elevation on the elec-
trocardiogram (ECG), and subsequent release
of biomarkers of cardiac necrosis.
The SPACE registry, a prospective registry of
ACS in 17 hospitals in the Kingdom of Saudi
Arabia (KSA) included hospitalized patients
with ACS over a 24 month period. Of the 5055
patients included, 2096 (41.5%) presented
with a STEMI.3 The prevalence of CAD risk fac-
tors in the Saudi population is higher than
that reported in European and US registries
including 58% of patients with diabetes melli-
tus (DM), the highest ever reported rate in an
ACS population. Patients presenting with ACS
were younger (mean age 58 years) compared
with populations reported in other registries.
41.5% of patients presenting with ACS had a
STEMI; only 14.8% received timely administra-
tion of thrombolytics (within 30 minutes of
presentation) and 17.5% of patients received
primary percutaneous coronary intervention
(PPCI). The Gulf RACE-2 registry, a multina-
tional study included patients from KSA,9 re-
ported 45.6% patients presenting with ACS
had STEMI with a mean age of 54 years and a
high prevalence of risk factors. 79% of STEMI
patients presented within 12 hours of symp-
tom onset with a median time from symptom
onset to hospital arrival of 178 minutes. In
spite of the earlier age of presentation with
STEMI, overall these patients had a 30 day
mortality of 9.9% and 1 year mortality of
11.5%.
Although registry data with baseline charac-
teristics, management practices and out-
comes have been published for the KSA popu-
lation, local studies of the interventions in this
population addressed in the guideline are not
available.
Methodology
To facilitate the interpretation of these guide-
lines; we briefly describe the methodology we
used to develop and grade recommendations
and quality of the supporting evidence.
6
Management of STEMI
The Saudi expert guideline panel selected the
topic of this guideline and all healthcare ques-
tions addressed herein using a formal prioriti-
zation process. For the selected questions we
updated existing systematic reviews on myo-
cardial infarction with ST-segment elevation
published in July 2013 by the National Clinical
Guideline Centre (NCGC) for the National In-
stitute for Health and Care Excellence (NICE).4
For each question, the McMaster guideline
working group updated the search strategy to
identify new studies and/or new systematic
reviews. When relevant, the meta-analyses
were updated. We also conducted systematic
searches for information that was required to
develop full guidelines for the KSA, including
searches for information about patients’ val-
ues and preferences, and costs and resource
use specific to the Saudi context (see Appen-
dix 2).
Next, we developed for each question an evi-
dence profile and an evidence-to-decision
(EtD) table following the GRADE (Grading of
Recommendations, Assessment, Development
and Evaluation) approach and shared them
with the panel members (see Appendix 1).5,10
The guideline panel was invited to provide
additional information, particularly when pub-
lished evidence was lacking. The final step
consisted of an in-person meeting of the
guideline panel in Riyadh on March 15 & 16,
2015 to formulate the final recommendations.
We used the GRADE evidence-to-decision
frameworks to follow a structured consensus
process and transparently document all deci-
sions made during the meeting. Potential con-
flicts of interests of all panel members were
managed according to the World Health Or-
ganization (WHO) rules.6
Grading of the quality of evidence
The GRADE working group defines the quality
of evidence as the extent of our confidence
that the estimate of an effect is adequate to
support a particular decision or recommenda-
tion.7 We assessed the quality of evidence
using the GRADE approach.
Quality of evidence is classified as “high”,
“moderate”, “low”, or “very low” based on
decisions about methodological characteris-
tics of the available evidence for a specific
health care problem. The definition of each
category is as follows:
High: We are very confident that the
true effect lies close to that of the es-
timate of the effect.
Moderate: We are moderately confi-
dent in the effect estimate: The true
effect is likely to be close to the esti-
mate of the effect, but there is a pos-
sibility that it is substantially different.
Low: Our confidence in the effect es-
timate is limited: The true effect may
be substantially different from the es-
timate of the effect.
Very low: We have very little confi-
dence in the effect estimate: The true
effect is likely to be substantially dif-
ferent from the estimate of effect.
Grading of the strength of recommendations
The GRADE working group defines the
strength of recommendation as the extent to
which we can be confident that desirable ef-
fects of an intervention outweigh undesirable
effects. According to the GRADE approach,
the strength of a recommendation is either
strong or conditional (also known as or called
weak) and has explicit implications.8 Under-
standing the interpretation of these two
grades either strong or conditional of the
strength of recommendations is essential for
sagacious clinical decision-making. (see Table
1)
As a quality measure for any practice guide-
line prior to publication, the final report have
been externally peer reviewed by a methodo-
logical expert who has not been involved in
this guideline development.
7
Management of STEMI
How to use these guide-
lines
The Ministry of Health of Saudi Arabia and
McMaster University Practice Guidelines pro-
vide clinicians and their patients with a basis
for rational decisions about the management
of ST-segment elevation myocardial infarc-
tion. Clinicians, patients, third-party payers,
institutional review committees, other stake-
holders, or the courts should never view these
recommendations as dictates. As described in
other guidelines following the GRADE ap-
proach, no guideline or recommendation can
take into account all of the often-compelling
unique features of individual clinical circum-
stances. Therefore, no one charged with eval-
uating clinicians’ actions should attempt to
apply the recommendations from these
guidelines by rote or in a blanket fashion.
Statements about the underlying values and
preferences, resources, feasibility, equity, ac-
ceptability as well as other qualifying remarks
accompanying each recommendation are its
integral parts and serve to facilitate an accu-
rate interpretation. They should never be
omitted when quoting or translating recom-
mendations from these guidelines if they in-
fluence the strength or direction of the rec-
ommendation.
Key questions
The following is a list of the clinical questions
selected by the panel and addressed in this
guideline.
1. Should fibrinolysis vs. delayed primary
percutaneous coronary intervention
(PPCI) be used for treatment of STEMI
in patients who present within 12
hours of symptom onset to hospitals
not capable of PPCI services?
2. Should facilitated percutaneous coro-
nary intervention (fPPCI) versus PPCI
be used in patients with STEMI?
3. Should routine thrombus extraction
devices during PPCI versus PPCI alone
be used for treatment of STEMI?
4. Should multi-vessel PPCI versus culprit
only PPCI be used in patients with
STEMI and multi-vessel coronary ar-
tery disease undergoing PPCI?
5. Should early revascularization versus
medical stabilization be used in pa-
tients with cardiogenic shock due to
STEMI?
6. Should immediate angiography fol-
lowed by PPCI where indicated be
used in patients with presumed STEMI
who are resuscitated but remain un-
conscious after a cardiac arrest?
7. Should high volume centres versus
low volume centres be used for PPCI
services?
8. Should rescue PCI, repeat fibrinolysis,
or conservative management be used
in patients with STEMI who fail to
reperfuse after fibrinolytic therapy?
9. Should routine early angiography ver-
sus routine deferred or selective an-
giography be used for STEMI success-
fully treated by fibrinolysis?
Recommendations
For each of the recommendations
below we describe the considerations and
judgements made by the panel on the availa-
ble evidence about the factors in the evi-
dence-to-decision framework (i.e. benefits
and harms of the options, resource use, feasi-
bility, acceptability, balance of desirable and
undesirable consequences, etc.). With respect
to patients’ values and preferences, unless
otherwise noted for specific questions, the
panel including the patient representative
considered that there is no important variabil-
ity or uncertainty in patients’ values and pref-
erences in the KSA setting for the outcomes
considered across the questions addressed
(i.e. mortality, stroke, reinfarction, heart fail-
ure, repeat revascularization, bleeding). The
panel considered that patients would place a
high value on benefits such as reduction in
8
Management of STEMI
mortality and lower value on potential ad-
verse effects.
Question 1: Should fibrinolysis vs. delayed
percutaneous coronary intervention (PPCI)
be used for treatment of STEMI in patients
who present within 12 hours of symptom
onset to hospitals not capable of PPCI ser-
vices?
Background: ST elevation myocardial infarction is
caused by complete occlusion of a coronary artery
by a thrombus causing cessation of downstream
blood flow. This results in myocyte (heart muscle
cell) death which rapidly progresses unless blood
flow is restored. Timely intervention to restore
flow is critical to myocardial salvage and restoring
heart function.
Restoration of coronary blood flow (reperfusion)
can occur by primary percutaneous coronary in-
tervention (PPCI) using mechanical techniques in
the cardiac catheterization laboratory or by
thrombolytics (clot dissolving drugs that can be
given intravenously). Due to ease of administra-
tion, thrombolytics can be initiated in any
healthcare setting. In contrast, PPCI requires
transfer to a facility that has a cardiac catheteriza-
tion laboratory that is capable of performing PPCI,
the time required to transfer the patient will add
to the delay in reperfusion. Delay in reperfusion
increases the risk of impaired left ventricular sys-
tolic function and death.11,12
Results of meta-analyses of randomized con-
trolled trials (RCT) have demonstrated that timely
PPCI is superior to thrombolysis with lower rates
of mortality, re-infarction and stroke.13,14 The ad-
vantage of PPCI over thrombolytics is diminished
with increasing PPCI-related time delay (the addi-
tional time lost before reperfusion due to transfer
of patient to a PPCI capable facility).
Timeliness of PPCI is assessed by the ‘door to bal-
loon time’ (DTB), defined as the time from arrival
at the hospital to inflation of the angioplasty bal-
loon in the infarct related artery. For thrombolyt-
ics, this measure is the ‘door to needle time’
(DTN), defined as the time from arrival to the
hospital to the administration of thrombolytics. In
addition to the DTB time, the PPCI related time
delay includes the additional time required for
transport to a PPCI capable hospital. This incorpo-
rates the additional time required to transfer the
patient to a PPCI capable facility instead of admin-
istering thrombolytics in the health care facility
where the patient initially presents.
This question reviews the impact of delays to
treatment on outcomes for ‘PPCI after transfer’
compared to thrombolytics administered at the
presenting facility. The data were reviewed to de-
termine if there is a PCI related time delay at
which fibrinolysis becomes more effective in pa-
tients presenting with STEMI.
The preferred agents for fibrinolysis are tissue
plasminogen activator (tPA) or tenecteplase
(TNKase), while streptokinase should be used if
tPA or TNKase are not available in a specific hospi-
tal or setting. Streptokinase is an antigenic
thrombolytic agent; significant levels of antistrep-
tokinase antibodies can form within a few days of
administration and can persist for 4 years in up to
50% of patients. The antibodies may cause an al-
lergic reaction or neutralize a further dose of
streptokinase and render it ineffective 15. Strepto-
kinase is not recommended if a repeat dose of
thromblytic is administered in a patient who has
received a dose of streptokinase in the past.
Summary of Findings: The 2012 NICE system-
atic review included 6 meta-regression studies
that addressed this question. A subsequent
literature search for the time period from No-
vember 2012 to November 2014 did not iden-
tify any new meta-regression studies. Among
the 6 meta-regressions included, 3 used study
level data,16,17,18 2 used individual patient data
compiled from randomized controlled
trials19,20 and one was based on a large regis-
try.21 The overall quality of evidence was
judged as very low.
Benefits of the Option: PPCI and fibrinolysis
are both accepted forms of reperfusion ther-
apy in patients presenting with STEMI within
12 hours of symptom onset. Benefits of reper-
fusion therapy are closely related to the time
9
Management of STEMI
from symptom onset to delivery of reperfu-
sion therapy; reperfusion therapy should be
delivered as soon as possible after presenta-
tion. Although PPCI decreases adverse out-
comes compared to thrombolytics, this bene-
fit decreases with increasing delays. Based on
all available evidence, the panel determined
that if PPCI can be performed within a total
delay of 120 minutes from first contact with
the patient to the time of the procedure, it is
superior to fibrinolysis with regard to 30 day
mortality based on the very low quality evi-
dence.
Harms of the Option: With longer duration of
delay related to transfer for PPCI, the rate of
adverse outcomes increased, if transfer to a
PPCI capable hospital cannot be achieved
within the specified timeframe, fibrinolysis is
the preferred choice of treatment.
Resource Use: No KSA specific data was identi-
fied. From the 2012 NICE systematic review,
two cost-utility analyses showed that PPCI
was cost effective compared to in-hospital
fibrinolysis, except at long PPCI-related time
delays. Based on data from the study by Asse-
burg,16 it was estimated that PPCI had a 90%
probability of being cost effective (at thresh-
old of £20,000 per QALY) based on average
PPCI-related time delay of 64 minutes, which
related to a median call-to-balloon time of
130 minutes. PPCI was less effective and more
costly compared to fibrinolysis for patients
transferred from hospital to a separate PPCI
centre with time delays of 100 minutes (me-
dian call-to-balloon time of 167 minutes). The
panel considered that up to the acceptable
time delay the resources required would be
small and that the incremental cost was small
relative to the net benefits.
Acceptability: The panel considered that both
intervention options are effective and ac-
ceptable to the patient population and to
stakeholders including clinicians. If either in-
tervention can be performed in a timely fash-
ion, PPCI is superior to fibrinolysis. However in
the absence of the ability for expedited trans-
fer to a PPCI capable facility, fibrinolysis pro-
vides improved outcomes compared to no
treatment.
Feasibility: Fibrinolysis is readily administered
in many health care facilities. PPCI is available
in limited hospitals. The panel considered
both options feasible, but noted that rapid
transfer to a PPCI capable hospital may pose
logistical challenges in the KSA setting. The
SPACE registry cited the infrequent use of
ambulances (5.1% in ‘own’ patients), traffic
congestion in major cities as potential reasons
for delays in presentation and transfer of pa-
tients.
Balance between desirable and undesirable
consequences: Based on the available evi-
dence suggesting equipoise between the two
treatment options at a time delay of approxi-
mately 120 minutes, the panel considered
that below this threshold of total time delay
the desirable consequences of delayed PPCI
compared to fibrinolysis would outweigh the
undesirable consequences. There is a decreas-
ing benefit of PPCI with considerable PPCI-
related time delay, but up to a delay of 120
minutes from first patient contact (including
transport time to PCI-capable facility) PPCI
was considered to result in better outcomes
for patients as compared to fibrinolysis. The
strength of recommendation was judged as
conditional due to very low quality evidence.
Recommendation 1:
The panel suggests using fibrinolytic therapy
over delayed PPCI if there is a total time de-
lay >120 minutes. (conditional recommenda-
tion, very low quality evidence)
Remarks:
The total time delay of 120 minutes
refers to the period from the first
contact with the patient to the pro-
vision of PPCI.
For patients presenting directly to a
PCI-capable facility the suggested
acceptable time delay to provision of
PPCI is 90 minutes (i.e. door-to-
balloon time).
10
Management of STEMI
Implementation Considerations and Monitoring:
The panel noted that in the KSA setting emergen-
cy medical services (EMS) are poorly developed,
therefore resulting in poor results for transport of
patients. In order to meet the desired threshold of
<120 minutes in total delay time where PPCI re-
sults in better outcomes for patients than fibrinol-
ysis, improvement in transport of patients to PPCI
capable facilities is required. As another consider-
ation, the panel also noted that EMS personnel in
the KSA are currently not certified to administer
fibrinolysis in transport, and therefore patients
may also experience longer delay times for fibri-
nolysis. For this recommendation the preferred
agents for fibrinolysis are tissue plasminogen acti-
vator (tPA) or tenecteplase (TNKase), while strep-
tokinase should be used if tPA or TNKase are not
available in a specific hospital or setting. In a pa-
tient with a prior history of administration of
streptokinase, due to the possibility of neutraliz-
ing anitibody formation and allergic reaction, a
repeat dose should not be used.
The SPACE registry 3 reported that of 1232
STEMI patients, 905 (73.5%) presented to
hospital at <12 hours of symptom onset. Only
8.3% of patients arrived to hospital in an am-
bulance. Alshahrani et al 22 reported in a 2014
study that there was a significant difference in
pre-hospital delay for male patients (median
5h) versus female patients (median 12.9h) in a
sample of 311 STEMI patients presenting to 3
hospitals in Riyadh between March 2011 and
August 2011. In a chart review of 536 patients
who underwent PPCI at King Abdulaziz Cardiac
Centre between September 2008 and Sep-
tember 2012, the average door-to-balloon
time was 87.7 minutes, with the average time
in 2012 reduced to 72 minutes.23 The results
of these studies support the panel’s assertion
that a focus on improvements in transport of
patients to PPCI capable facilities is required
to help meet the suggested threshold of time
delay to improve patient outcomes.
Question 2: Should facilitated percutaneous
coronary intervention (fPPCI) versus percu-
taneous coronary intervention (PPCI) be used
in patients with STEMI?
Background: ST elevation myocardial infarc-
tion (STEMI) is usually caused by thrombotic
occlusion of a coronary artery causing cessa-
tion of blood flow resulting in myocardial cell
necrosis. The mainstay of treatment is resto-
ration of blood flow by mechanical (PPCI) or
pharmacological (thrombolytics) means.
Pharmacologic agents can be administered in
the field or the emergency room before PPCI
to facilitate restoration of flow or prevention
of propagation of thrombus in the coronary
artery. Facilitated PPCI is a strategy in which
pharmacologic agents are given to the patient
with STEMI before the patient arrives in the
catheterization lab. The drugs that have been
used for facilitated PPCI include fibrinolytics
and glycoprotein 2b/3a inhibitors or a combi-
nation of these 2 agents. These agents may
increase the success of PPCI but may also
cause increased adverse effects in the form of
bleeding.
The term ‘pharmacoinvasive therapy’ has
been inconsistently used to refer to various
pharmacologic interventions administered
before PCI. These have included full dose fi-
brinolytics, reduced dose fibrinolytics and
other agents to improve perfusion; a strategy
of full dose fibrinolytics followed by rescue
PCI24 as needed and use of non-hematologic
pharmacologic agents such as complement
antibodies and caspase inhibitors.25 To avoid
misinterpretation, the term ‘facilitated PPCI’ is
being used in this context this question will
address the use of fibrinolytic agents or gly-
coprotein 2b/3a inhibitors administered be-
fore arrival to the cardiac catheterization la-
boratory in patients undergoing PPCI.
Summary of Findings: Our literature review
identified two new studies26,27 that were add-
ed to our meta-analysis and that were not
included in the NICE systematic review28-49.
The quality of evidence for the outcomes was
11
Management of STEMI
low to very low, with the overall quality of
evidence judged as very low.
Benefits of the Option: Although facilitated
PPCI increased vessel patency of the infarct
related artery in preliminary studies, this did
not translate into improved patient important
outcomes. Benefit of facilitated PPCI was not-
ed for only the outcome of heart failure at 6
38,36 to 12 26 months. The relative risk of heart
failure was 0.48 (95% confidence interval of
0.28-0.83) in patients randomized to a fPPCI
strategy. The evidence was based on a total of
55 events among 745 patients enrolled in the-
se 3 trials that reported long term heart fail-
ure outcome and was judged to be of low
quality. No benefit was found for the outcome
of long term mortality, long term stroke, long
term reinfarction and long term repeat revas-
cularization. The panel noted that in the ab-
sence of a significant reduction in mortality,
the reduction in heart failure seems to be of
lesser significance, and the panel determined
that the desirable anticipated effects of fPPCI
are probably not large.
Harms of the Option: The fPPCI group incurred
significantly higher rates of both major (rela-
tive risk of 1.47; 95% confidence interval of
1.05-2.05) and minor (relative risk of 1.43;
95% confidence interval of 1.20-
1.71)bleeding. The panel concluded that the
undesirable anticipated effects of fPPCI are
probably not small.
Patients’ Values and Preferences: The panel
noted that for the outcome of minor bleeding,
there could possibly be some variability in
how patients view the outcome in the KSA
setting, but overall noted that there probably
is no important uncertainty or variability in
patients’ values and preferences.
Resource Use: The panel noted that imple-
mentation of fPPCI requires well developed
emergency medical services, and that re-
sources would be required to implement EMS
transfer procedures to allow fPPCI. Additional
training of personnel would be required for
the drugs were to be administered before
hospital admission, and that the resources
required for this would not be small for mini-
mal benefit with increased harm to patients.
Acceptability: Given the minimal net benefit
and the increase in harm for patients, as well
as the additional resources required for fPPCI,
this option was found by the panel as not ac-
ceptable to the key stakeholders.
Feasibility: The panel concluded that the op-
tion of fPPCI would not be feasible in the KSA
setting due to the lack of EMS services to ad-
minister fibrinolytic agents or glycoprotein
2b/3a inhibitors before arrival to the cardiac
catheterization laboratory and that training
would be required.
Balance between desirable and undesirable
consequences: The panel considered there
was more harm than benefit when using fPP-
CI, in addition to the feasibility and resource
use issues identified for the KSA setting (i.e.
lack of EMS), and therefore the undesirable
consequences outweighed desirable conse-
quences. The strength of recommendation is
conditional due to very low quality evidence.
Recommendation 2:
The panel suggests against using fPPCI in pa-
tients with STEMI. (conditional recommen-
dation, very low quality evidence)
Remark:
Facilitated PPCI (fPPCI) should not
be confused with a pharmacoinva-
sive PPCI strategy
Implementation Considerations and Monitor-
ing: In the KSA there are currently not many
PPCI centres doing fPPCI procedures, and the
panel considered that no specific implementa-
tion considerations or active monitoring for
this recommendation are required.
12
Management of STEMI
Question 3: Should routine thrombus extrac-
tion devices during percutaneous coronary
intervention (PPCI) versus percutaneous cor-
onary intervention (PPCI) alone be used for
treatment of STEMI?
Background: STEMI is usually caused by com-
plete occlusion of a major coronary artery by
a thrombus. The initial event leading to a
STEMI is commonly rupture or erosion of an
atheromatous plaque. This exposes the
thrombogenic plaque contents to the circulat-
ing blood activating the coagulation cascade
and platelets which leads to formation of the
occlusive thrombus. This thrombus is loosely
adherent to the vessel wall and while at-
tempting to open the occluded artery during
PPCI, the thrombus may get dislodged and
migrate downstream occluding smaller ves-
sels. The distal obstruction may continue to
cause myocardial damage and negate the
beneficial effects of reopening the coronary
artery.
In an attempt to limit damage caused by distal
embolization of the thrombus, devices to re-
move the thrombus during PPCI have been
extensively studied. These range from simple
hollow aspiration catheters to powered me-
chanical devices which can be used to frag-
ment and aspirate the thrombus if the throm-
bus burden appears large. The disadvantage
of using these devices is the added time to the
procedure and the complications associated
with the use of the device.
Several small studies have suggested better
myocardial perfusion and decreased infarct
size with thrombectomy. New trials evaluating
the effect of thrombectomy on patient im-
portant outcomes have been published in-
cluding 2 recent large trials which together
enrolled more patients than all previous trials.
The first of these is the TASTE trial published
in 2013 50 (1 year results published in 2014 51).
This trial enrolled 7244 patients and random-
ized them to PPCI alone or PPCI with throm-
bus aspiration. Crossover from one group to
the other was discouraged, 93.9% of the pa-
tients in the thrombus aspiration group un-
derwent thrombus aspiration; in addition,
4.9% of patients in the PPCI alone group un-
derwent thrombus aspiration. The second trial
pulished in 2015 is the TOTAL52 trial which
enrolled 10,732 patients and randomly as-
signed them to PPCI alone or routine manual
thrombectomy. In this trial, ‘bailout throm-
bectomy’ was allowed if there was failure of
the initial PPCI alone strategy, defined as
thrombolysis in myocardial infarction (TIMI)
flow grade of 0 or with a large thrombus after
predilation or the persistence of a large
thrombus after stent deployment. The rate of
crossover was 4.6% from thrombectomy to
PPCI alone and 1.4% from PPCI to throm-
bectomy. Bailout thrombectomy was per-
formed in 7.1% in the PPCI alone group. Pre-
specified subgroup analyses in this trial in-
cluded comparisons based on thrombus bur-
den, duration of symptoms, initial TIMI flow,
age, center volume and type of MI (anterior
versus nonanterior).
Summary of Findings: In addition to the stud-
ies included in the NICE systematic review 53-
72, we identified 4 additional trials 50-52,73,74
that addressed the question of thrombus ex-
traction during PPCI. One of them 74 com-
pared rheolytic thrombectomy with manual
thrombus aspiration, and was not included in
the meta-analysis. The results of a large trial,
the TOTAL 52 trial assessing thrombus aspira-
tion, were published in March of 2015 and,
given its importance, the entire literature
search was updated to April 2015 for this rec-
ommendation.The outcomes were analyzed
separately by subgroup for thrombus aspira-
tion and mechanical thrombus extraction (see
evidence profile in Appendix 1). The overall
quality of evidence was rated as moderate.
Benefits of the Option: Target vessel revascu-
larization in the long term (6 to 12 months)
was performed less frequently (relative risk
0.85, 95% confidence interval 0.73 1.00) in
the thrombus aspiration subgroup, with an
absolute effect of 10 fewer per 1000 patients
(95% confidence interval: from 0 fewer to 18
fewer). There was no difference in the me-
chanical thrombus extraction subgroup or the
13
Management of STEMI
overall group (relative risk 0.90, 95% confi-
dence interval 0.80-1.01) for this outcome. No
benefit was noted for any of the other out-
comes including mortality and re-infarction,
and the panel concluded that overall the de-
sirable anticipated effects are probably not
large.
Harms of the Option: There was increased risk
of stroke within 30 days in the subgroup of
patients that underwent mechanical throm-
bus extraction (relative risk 2.03, 95% confi-
dence interval 1.19-3.47), translating to an
absolute effect of 3 more strokes per 1000
patients (95% confidence interval: from 1
more to 8 more) and in the thrombectomy
group overall (relative risk 1.50, 95% confi-
dence interval 1.00-2.24), with an absolute
effect of 2 more strokes per 1000 patients
(95% confidence interval: from 0 fewer to 5
more). The risk of major bleeding was similar
between the thrombectomy group overall and
the control group undergoing PPCI alone.
Resource Use: Based on data from the NICE
systematic review the panel discussed the
cost difference between thrombus aspiration
devices (£110£125) and mechanical throm-
bus extraction devices (£1200) and noted that
in the KSA setting there is a similar cost differ-
ence between the two types of devices. The
panel considered that for mechanical throm-
bus extraction devices the resources required
would not be small, and that for thrombus
aspiration devices resources required may be
small but total volume costs for routine use
would need to be considered. However, it was
determined that in consideration of the high
cost of the primary PCI procedure (estimated
at 20,000 SAR for Ministry of Health hospitals)
the additional resources required for throm-
bus aspiration would likely be small. With re-
spect to incremental cost relative to the net
benefit, the panel concluded that the incre-
mental cost would probably not be small rela-
tive to the net benefits of both types of devic-
es.
Acceptability: The panel considered that for
routine use, thrombus aspiration would prob-
ably be acceptable to key stakeholders includ-
ing clinicians, but for mechanical thrombus
extraction the option would probably not be
acceptable due to the additional time re-
quired to conduct the procedure when using
the device.
Feasibility: The panel considered that the use
of both types of devices would be feasible in
the KSA setting given current availability.
Balance between desirable and undesirable
consequences: Given the lack of benefit of the
options in the overall group on patient im-
portant outcomes, the increase in stroke with-
in 30 days as an undesirable consequence
outweighing the marginal benefit of decrease
in long term revascularization in the thrombus
aspiration subgroup, and the resource use
required, the panel concluded that that the
undesirable consequences of routine throm-
bectomy with either thrombus aspiration or
mechanical thrombus extraction outweigh the
desirable consequences.
Subgroup considerations: The panel consid-
ered whether the desirable consequences
may outweigh the undesirable consequences
in the group of patients with large visible clots
and whether routine use of thrombus aspira-
tion would be justified. The TOTAL trial pro-
vided preplanned subgroup analysis of the
primary outcome (composite of cardiovascu-
lar death, recurrent myocardial infarction,
cardiogenic shock, or class IV heart failure) for
the subgroups of patients with TIMI (Throm-
bolysis in Myocardial Infarction) grade >= 3
(largest dimension of thrombus 0.5 to 2.0
times the diameter of the vessel) and TIMI
grade >=4 (largest dimension of thrombus
more than 2.0 times the diameter of the ves-
sel). The results in both subgroups were simi-
lar to the overall results suggesting no appar-
ent benefit of thrombus aspiration in patients
with TIMI thrombus grade >=3 (hazard ratio
0.96, 95% confidence interval 0.82-1.12) and
>=4 (hazard ratio 0.97, 95% confidence inter-
val: 0.82-1.14). (see table in Appendix 3 -
Question 3)
14
Management of STEMI
Note that the recommendation is for routine
use of thrombus aspiration in the treatment
of STEMI, and does not preclude the use of
thrombus aspiration as a bail out procedure
when deemed necessary. Bailout throm-
bectomy was performed in the TOTAL trial for
patients with a large thrombus burden if there
was a failure of the PPCI strategy alone, which
was defined as TIMI flow 0 or 1 with a large
thrombus after balloon predilation or persis-
tence of a large thrombus after stent deploy-
ment. In the trial, bailout thrombectomy was
performed in 7.1% (355 patients) in the PPCI
alone control group.
Recommendation 3:
The panel recommends against routine use
of aspiration or thrombus extraction devices
in patients with STEMI. (strong recommen-
dation, moderate quality evidence)
Implementation Considerations and Monitor-
ing: The panel noted there is little routine use
of thrombus aspiration or mechanical throm-
bus extraction devices in the KSA, and that
there are probably no additional require-
ments for implementation of this recommen-
dation.
Question 4: Should multi-vessel PPCI versus
culprit only PPCI be used in patients with
STEMI and multi-vessel coronary artery dis-
ease undergoing PPCI?
Background: In patients undergoing PPCI for
STEMI, significant stenosis may be identified
in non-infarct related arteries. Many patients
have multi vessel disease with significant ste-
nosis in arteries other than the culprit vessel.
The management of the additional lesions at
the time of PPCI is controversial.
The strategy of treating all significant lesions
at the time of PPCI has the advantage of com-
plete revascularization thus potentially de-
creasing future cardiac events. The disad-
vantage is the additional time and contrast
used for the additional PCIs and the potential
complications associated with the longer pro-
cedure.
Until recently most of the evidence available
to answer this question was based on obser-
vational studies. More recently, RCTs have
been published addressing this question. In
these trials, the timing of the non- infarct re-
lated artery intervention varies from index
procedure, repeat procedure during index
hospitalization and within 3-4 weeks of the
STEMI. For the purpose of this question, trials
evaluating multi-vessel PCI during index pro-
cedure were considered.
Summary of Findings: The previous NICE sys-
tematic review identified several observation-
al studies and 2 RCTs75,76. The data from ob-
servational studies were heterogeneous and
overall there was no clear indication of bene-
fit from either strategy.
Since the publication of the NICE systematic
review, 2 more RCTs 77,78 have been published.
One of these trials77 was presented at the Eu-
ropean Society of Cardiology meeting in Sep-
tember of 2014 and was published in March
of 2015 prior to the panel meeting. The litera-
ture search for this recommendation was up-
dated to March 2015. A large multicenter trial
(COMPLETE trial, ClinicalTrials.gov Identifier:
NCT01740479) is currently enrolling patients
with a projected recruitment of 3900 and an
estimated study completion date of Decem-
ber 2018.
Due to inconclusive evidence based on obser-
vational studies and additional RCT results
available since the NICE publication, the stud-
ies included to address this question in these
guidelines were limited to RCTs. 4 RCTs were
included, 2 of these trials performed the mul-
ti-vessel PCI exclusively during the index pro-
cedure 75,78, the third trial compared three
groups; a group with intervention during in-
dex procedure and a group with staged revas-
cularization in addition to a control group (the
data for the groups randomized to complete
revascularization during the index procedure
15
Management of STEMI
and control were used in the meta analysis;
staged revascularization group was not in-
cluded) and in the fourth trial, 64% of patients
in the multi-vessel intervention group re-
ceived complete revascularization during in-
dex procedure and the remaining during the
index hospitalization - the decision to stage
the procedure was based on clinical reasons
made by the operator performing the PCI; the
outcomes were not separated based on com-
plete revascularization performed during in-
dex procedure versus index hospitalization.
Benefits of the Option: There meta-analysis
showed for long term (>1 year follow up) mor-
tality a relative risk of 0.63 for multi-vessel
PCI, but with a wide confidence interval of
0.37 to 1.05, translating to an absolute effect
of 27 fewer deaths per 1000 patients with
multi-vessel PCI (95% confidence interval:
from 46 fewer to 4 more). The relative risk of
reinfarction was significantly lower (relative
risk 0.37, 95% confidence interval 0.19-0.71)
in the multi-vessel PCI group. As expected,
due to complete revascularization during the
index procedure, rate of revascularization was
significantly lower (relative risk 0.37, 95% con-
fidence interval of 0.26-0.53) in the multi-
vessel PCI group.
Harms of the Option: No specific harm was
identified with multi-vessel PCI based on the
meta-analysis. Contrast induced nephropathy
was variably reported, there was no signifi-
cant difference in this outcome in the 2
groups based on available data (limited data
available in 3 of the 4 published studies, rela-
tive risk of 0.55 in favour of multi-vessel PCI;
95% confidence interval 0.16-1.89). The panel
additionally noted that every PCI procedure
carries risk, and that with multi-vessel PCI the
time of the procedure is extended.
Resource Use: Resource use with multi-vessel
PCI would be increased due to increased use
of lab time, and more stents, contrast and
other supplies required. This, however, is off-
set by lower resource use during follow up
due to decreased incidence of myocardial in-
farctions and revascularization. No data spe-
cific for the KSA setting were available, but
one cost-consequence analysis 75 identified in
the NICE systematic review reported that cul-
prit only PCI was more costly over 12 months
as compared to immediate multi-vessel PCI
based on a sample of 69 patients. The panel
considered that the incremental cost of multi-
vessel PCI was probably small relative to the
net benefits.
Acceptability: The panel noted that there may
be reluctance to accept multi-vessel PCI in
patients with STEMI as some providers may
question the reason for the procedure (i.e. as
compared to CABG procedure for the patient)
and payers and hospital administrators may
also be reluctant to accept the procedure giv-
en the resource use.
Feasibility: Multi-vessel PCI was viewed as a
feasible option to implement. Consideration
should be given to the increased procedure
time in the cardiac catheterization laboratory
to perform multi-vessel PCI, with scheduling
constrains that may occur.
Balance between desirable and undesirable
consequences: The panel considered that mul-
ti-vessel PCI as compared to culprit-only PCI
was shown to probably have large desirable
effects relative to undesirable effects with
overall net benefit for the patient. The
strength of recommendation was conditional
based on the low quality evidence as well as
some uncertainty about the resource use in
the local healthcare setting and acceptability
from providers and administrators.
16
Management of STEMI
Recommendation 4:
The panel suggests multi-vessel PPCI over
culprit-only PCI for patients with multi-vessel
coronary artery disease undergoing PPCI.
(conditional recommendation, low quality
evidence)
Remarks:
This recommendation is based on
evidence with data predominantly
from patients undergoing multi-
vessel PCI during the index proce-
dure, but the procedure may also be
considered during the index hospital-
ization.
This recommendation does not apply
to patients with cardiogenic shock.
Implementation Considerations and Monitor-
ing: As the results of the COMPLETE trial will
be available in December of 2018, the panel
has set this as the expiration date for this rec-
ommendation. The recommendation will be
reviewed and revised as necessary at that
time.
Given the considerations around acceptability
of multi-vessel PCI by the providers the panel
recommends that a policy be developed to
outline how interaction between surgeons
and cardiologists in hospitals should be dealt
with as part of the care pathway for ACS and
STEMI patients, where considerations such as
availability and providing procedures such as
CABG can be outlined.
Question 5: Should early revascularization
versus medical stabilization be used in pa-
tients with cardiogenic shock due to STEMI?
Background: Around 5% to 8% of patients
admitted to hospitals with STEMI are in cardi-
ogenic shock at the time of presentation. A
state of decreased end organ perfusion due to
low cardiac output is termed cardiogenic
shock. In patients with STEMI, this can be due
to pump failure due to myocardial dysfunction
from the STEMI; due to mechanical complica-
tions including acute mitral regurgitation or
septal or free wall rupture or due to malig-
nant arrhythmias. These patients have a high
mortality with greater than 50% in hospital
mortality.79,80
In patients with STEMI, early revascularization
is the cornerstone of treatment to improve
perfusion and limit myocardial damage. How-
ever, patients in cariogenic shock may be too
unstable and may benefit from early medical
stabilization.
Summary of Findings: The NICE systematic
review identified 2 RCTs with results included
in 10 79,81-89 publications. We identified no
new trials were identified in our updated sys-
tematic review. The overall quality of evi-
dence was moderate.
Benefits of the Option: The analysis showed
that mortality at one year was significantly
lower in the intervention group with early re-
vascularization as compared to medical stabi-
lization (relative risk 0.80, 95% confidence
interval 0.67-0.97) based on one study, trans-
lating to an absolute effect of 134 fewer
deaths per 1000 patients (95% confidence
interval: from 221 fewer to 20 fewer). Short
term mortality based on two studies was also
lower in the early revascularization group but
with a wide confidence interval (relative risk
0.84, 95% confidence interval 0.70-1.02), as
was class III or IV heart failure at 2 weeks fol-
low-up (relative risk 0.64, 95% confidence in-
terval 0.36-1.15).
Harms of the Option: There were no harms
identified for early revascularization based on
the outcomes reported in these studies.
Resource Use: No data specific to the KSA set-
ting were available for costs and cost-
effectiveness. The panel considered that the
resources required for early revascularization
are probably not small, considering all costs
including downstream costs. However, the
incremental cost was considered probably
17
Management of STEMI
small relative to the net benefit, in cosidera-
tion of the significant improvement in morali-
ty at 1 year.
Acceptability and Feasibility: The option of
early revascularization was viewed as ac-
ceptable to all key stakeholders. However,
given that patients with cardiogenic shock
would require to be transferred to a PCI capa-
ble facility if the hospital they present to does
not offer the procedure, and that there are
difficulties with universal access to PCI in the
KSA the option was viewed as probably not
feasible for all patients in all settings.
Balance between desirable and undesirable
consequences: A high weight was placed on
the benefits of the intervention for patients
and the panel concluded that desirable con-
sequences clearly outweigh undesirable con-
sequences. The panel considered that pa-
tients with cardiogenic shock are already at
high risk, supporting intervention with early
revascularization.
Recommendation 5:
The panel recommends early revasculariza-
tion for patients with cardiogenic shock due
to STEMI. (strong recommendation, moder-
ate quality evidence)
Subgroup Considerations: When a significant
delay is expected for patients for early revas-
cularization with PPCI, full conventional ther-
apy, including fibrinolytics, may be consid-
ered.
Implementation Considerations and Monitor-
ing: The feasibility issues outlined above need
to be addressed to allow full implementation
of this recommendation. As there are issues in
the KSA healthcare setting with universal ac-
cess to PCI, particularly in hospitals in areas
peripheral to large urban centres where cath-
eterization labs and PCI-capable facilities are
available, focus should be placed on develop-
ing PCI services to improve access. The devel-
opment of catheterization labs and training of
personnel is desirable in peripheral hospitals.
Question 6: Should immediate angiography
followed by PPCI where indicated be used in
patients with presumed STEMI who are re-
suscitated but remain unconscious after a
cardiac arrest?
Background: A considerable proportion of
patients with STEMI present as out-of-hospital
cardiac arrest; one study estimated that a
third of patients with STEMI present as sud-
den cardiac death 90. Emergency medical per-
sonnel attempt resuscitation in the majority
of out of hospital cardiac arrests, however
only a minority of these patients achieve re-
turn of spontaneous circulation (ROSC) 90. Of
the patients who are admitted to a hospital
with ROSC, most are unconscious in the im-
mediate period following the resuscitation.
During this time, a variety of treatments may
be indicated and providers may need to prior-
itize treatment options based on the condi-
tion of the patient and availability of treat-
ment options. It is not clear if immediate PPCI
is beneficial compared to stabilization in the
intensive care unit prior to PPCI.
Overall, in the KSA emergency medical ser-
vices are poorly developed, and particularly in
non-urban areas in the KSA there may not be
extensive EMS and resuscitation may not be
attempted on many patients with cardiac ar-
rest. This question addresses management of
patients who have been successfully resusci-
tated from a cardiac arrest with ROSC.
Summary of Findings: Three studies 91-93 were
identified based on the literature search in
the previously published NICE systematic re-
view. We did not identify additional studies in
our update of the systematic review. The me-
ta-analysis included observational studies and
the overall quality of evidence was judged as
very low.
Benefits of the Option: Mortality at 30 days
was significantly lower (relative risk 0.51, 95%
18
Management of STEMI
confidence interval 0.38-0.69) in patients
treated with immediate angiography and PCI.
Incidence of stroke at 30 days was reported
only in one study and this was significantly
lower in the patients treated with immediate
angiography and PCI (relative risk 0.5, 95%
confidence interval 0.28-0.88)
Harms of the Option: No harms were identi-
fied based on the outcomes reported in these
studies.
Resource Use: The resource use required for
immediate angiography followed by PCI was
judged as not small, taking into consideration
the costs for the procedure and in particular if
transfer of the patient is required. However,
the panel noted that the incremental cost rel-
ative to the net benefit is probably small given
the large benefit for patients shown in the
meta-analysis.
Acceptability: The option of immediate angi-
ography followed by PCI for patients with car-
diac arrest was viewed as probably not ac-
ceptable to key stakeholders in the KSA set-
ting as the panel noted that at arrival to hos-
pital providers may not want to accept the
patient and that these patients with out of
hospital arrest may be rejected. For patients
with in-hospital cardiac arrest, this would not
be applicable and patients would receive
treatment immediately.
Feasibility: The panel noted that the option of
immediate angiography followed by PCI is also
probably not feasible in the KSA setting. It is
difficult for patients with out of hospital car-
diac arrest to make it to the hospital due to
poorly developed EMS. Cases of patients who
suffer an out of hospital cardiac arrest and are
resuscitated, achieving return of spontaneous
circulation, are infrequent. Additionally, as
previously noted there is a lack of access to
PCI services for the overall population in the
KSA, with 48 cardiac centres with catheteriza-
tion labs currently operating, but due to the
geographical distribution and concentration of
these centres in urban areas, a large portion
of the population is left without access. There-
fore, patients with out of hospital arrest with
poor prognosis would be competing for lim-
ited spaces for PCI.
Balance between desirable and undesirable
consequences: The desirable consequences
probably outweigh undesirable consequences
for immediate angiography followed by PCI
for patients with cardiac arrest who are resus-
citated but remain unconscious. In considera-
tion of the probably large benefit for patients
with reduction in morality, but issues of feasi-
bility and acceptability in the KSA healthcare
setting, as well as overall very low quality evi-
dence based on observational studies, the
strength of the recommendation is condition-
al.
Recommendation 6:
The panel suggests immediate angiography
followed by PCI where indicated over usual
care in patients with presumed STEMI who
are resuscitated but remain unconscious af-
ter a cardiac arrest. (conditional recommen-
dation, very low quality evidence)
Remarks:
For patients with unwitnessed out of
hospital arrest, without documented
time of arrest, the clinician may re-
evaluate the patient for PCI with de-
tailed assessment of the patient’s
neurological status before pro-
ceeding with a potentially futile
intervention.
Subgroup Considerations: A subgroup consid-
eration was made for in-hospital versus out of
hospital cardiac arrest, and in the latter for
witnessed versus unwitnessed arrest. The
panel noted that for patients with unwit-
nessed out of hospital cardiac arrest, without
documented time of arrest, the patient may
be re-evaluated and assessed by a clinician,
with detailed assessment of the patient’s neu-
rological status before proceeding with a po-
tentially futuile intervention.94
19
Management of STEMI
It may be difficult to establish STEMI in pa-
tients with out of hospital arrest who remain
unconscious, particularly in the case of unwit-
nessed arrest where there will be further un-
certainty for the patient’s prognosis. This con-
sideration was made in the context of the dis-
cussion about feasibility and difficulties with
access to PCI services for the KSA population.
Research possibilities: Given the infrequent
occurrence of cardiac arrest patients arriving
to hospital with ROSC, the panel suggests a
registry study and auditing to determine how
many patients with cardiac arrest with pre-
sumed STEMI make it to a catheterization lab
and what their outcomes are in the KSA set-
ting.
Question 7: Should high volume centres ver-
sus low volume centres be used for PPCI ser-
vices?
Background: Success of percutaneous coro-
nary intervention (PCI) depends on individual
expertise of the operator and the quality of
supporting staff and infrastructure. These in-
clude appropriate facilities, trained staff and
an ongoing volume of procedures to attain
and sustain excellent procedural outcomes.
Over time staff attain a level of expertise
which leads to lower complications and better
outcomes. In addition, primary percutaneous
coronary intervention is a more complex pro-
cess that requires communication and collab-
oration between the ambulance services,
emergency department, clinical and interven-
tional cardiology and other clinical and non-
clinical services at the hospital. Furthermore,
the cardiac catheterization laboratory team
must be available to perform the procedure at
any time of day or night to deliver timely and
efficient PPCI.
Several studies have identified an inverse rela-
tionship between hospital volumes and ad-
verse outcomes for PPCI. Addressing this
question is a healthcare systems issue. Pref-
erential referral of PPCI procedures to high
volume centers needs to be balanced with the
need for centers in remote locations that can
provide timely access to PPCI for the popula-
tion. This question addresses the extent to
which procedural volumes influence patient
outcomes.
Summary of Findings: Five publications 95-99
were identified in the previously published
NICE systematic review. Our updated system-
atic review included one additional publica-
tion.100 The studies identified were observa-
tional registry studies reporting on the out-
come of in-hospital mortality. One study re-
ported on in-hospital stroke and major bleed-
ing. Data is reported for in-hospital mortality
only from five registry studies, and the data
was not pooled across studies due to differ-
ences in reporting of the outcomes and defini-
tion of high-, medium- and low-volume cen-
tres. The overall quality of evidence was very
low.
Benefits of the Option: Each of the 5 registry
studies showed a trend for decreasing in-
hospital mortality with higher volume of PPCI
procedures performed per year (see evidence
profile in Appendix 1). The number of proce-
dures per year defining a low-, medium-, and
high-volume centre varied between the stud-
ies. The trend in decreasing in-hospital mor-
tality was observed when comparing low-
volume versus medium-volume centres, as
well as medium-volume versus high-volume
centres. Higher volume centers were there-
fore shown to have a lower risk for the out-
come of in-hospital mortality after PPCI for a
STEMI.
Harms of the Option: No data were available
on harms with respect to patient-important
outcomes for low-volume vs. high-volume
centres. The panel noted that limiting PPCI
services to high volume centers would likely
result in an increase in the time taken to
transfer patients with STEMI to a PPCI-capable
facility.
Resource Use: No data was available on re-
source use or cost-effectiveness of high-
volume versus low-volume centres. The panel
20
Management of STEMI
considered that the resources required for
prioritizing PPCI to high-volume centres would
probably be small and incremental cost would
probably be small relative to the net benefit
of reduction in in-hospital mortality.
Impact on Health Equity: The panel noted that
prioritizing high-volume centres for PPCI ser-
vices would improve patient outcomes and
that in general increasing volume at existing
low-volume centres would improve access for
patients to PPCI services, thereby probably
reducing health inequity in the KSA setting.
Acceptability: Prioritizing high-volume centres
for PPCI services was found as probably ac-
ceptable to key stakeholders. However, the
panel noted that patients' access to PPCI
would be reduced if PPCI services were to be
restricted to high volume centers only.
Feasibility: The feasibility of prioritizing high-
volume centres for PPCI services was uncer-
tain as it is a healthcare system issue that will
require input and debate from policy makers.
The recommendation needs to be addressed
as a health systems issue with logistical sup-
port and planning to improve centre volumes
and patient access overall in the KSA setting.
Balance between desirable and undesirable
consequences: The desirable consequences of
prioritizing high-volume centres for PPCI ser-
vices probably outweigh the undesirable con-
sequences if healthcare system changes are
implemented to improve timely access to high
volume centers. Higher volume centres were
shown to improve patient outcomes and have
a lower risk of in-hospital mortality. There is
no restriction set on centre size so as to not
further reduce access for patients in the KSA
setting, and expansion of PCI services to in-
crease volume should be prioritized. The
strength of recommendation is conditional
due to uncertainty about feasibility as well as
very low quality evidence.
Recommendation 7:
The panel suggests prioritizing the manage-
ment of patients with STEMI to high volume
centres. (conditional recommendation, very
low quality evidence)
Remark:
The implementation of this recom-
mendation should not restrict care
for patients who require PPCI in set-
tings where only low-volume centres
are available.
Implementation Considerations and Monitor-
ing: Implementation of this recommendation
should focus on prioritizing expansion of PPCI
services to increase volume, in particular in
existing low-volume centres. The goal for the
KSA healthcare system is to improve access
for patients to PPCI services, where there is
currently lack of access, which should not in-
volve restricting access from current low-
volume centres. The consideration for increas-
ing volume at existing centres is a healthcare
system issue that is in concordance with the
previously discussed need for improvement in
transport and transfer of patients to PPCI-
capable facilities to improve access for pa-
tients across the KSA.
Research possibilities: Based on the considera-
tions for the KSA healthcare setting and cur-
rent levels of access to PPCI services for STEMI
patients, the panel suggests research to as-
sess outcomes for patients receiving PPCI at
low-volume centres versus treatment with
thrombolytics.
Question 8: Should rescue PCI, repeat
fibrinolysis, or conservative management be
used in patients with STEMI who fail to
reperfuse after fibrinolytic therapy?
Background: STEMI is usually caused by
thrombotic occlusion of a major coronary ar-
tery. Fibrinolytic therapy restores flow in the
coronary artery by lysing the thrombus lead-
ing to preserved myocardial function and de-
21
Management of STEMI
creased mortality. Complete reperfusion with
normal flow in the infarct related artery is
found only in approximately 50% of the pa-
tients who receive fibrinolytic therapy. In
some patients, delayed, sluggish flow is re-
stored with complete filling of the distal coro-
nary territory. Fibrinolysis fails to reperfuse
the distal myocardium in approximately 40%
of patients101. This is identified clinically by
persistent ST elevation (<50% ST segment
resolution on a follow up electrocardiogram
60-90 minutes after administration of fibrino-
lytics). Incomplete restoration of distal flow
does not improve survival. These patients may
benefit from additional interventions to
reperfuse the myocardium102.
Options for further revascularization include
repeat fibrinolysis and immediate referral for
coronary angiography and PCI (rescue PCI) to
restore distal flow. Rescue PCI requires emer-
gency transfer of the patient to a hospital
with a cardiac catheterization laboratory with
PCI capabilities. A third alternative is con-
servative therapy without repeat fibrinolysis
or rescue PCI.
Summary of Findings: The previously pub-
lished NICE systematic review identified 10
studies 103-112 that were included in our meta-
analysis. We did not identify additional stud-
ies in our updated systematic review. We ana-
lyzed and presented the comparisons for the
3 options (rescue PCI, repeat fibrinolysis and
conservative therapy) separately and pre-
pared evidence profiles for each comparison
rescue PCI versus conservative therapy, re-
peat fibrinolysis versus conservative therapy
and rescue PCI versus repeat fibrinolysis.
Overall the quality of evidence was low for
each of the 3 comparisons. One of the studies
110 included in the repeat fibrinolysis versus
conservative management had a higher than
expected mortality in the conservative man-
agement arm (29%) and a higher rate of angi-
na (40% versus 6.6%) and urgent revasculari-
zation (31% versus 2.2%) in the repeat fibri-
nolysis arm compared to the conservative
management arm - successful thrombolysis
should decrease the incidence of angina and
need for urgent revascularization. This was a
small study (total 90 patients) and although
labelled as a randomized double blind study,
there were significant unexplained differences
between the two groups (45 patients each).
Benefits of the Option: In the comparison be-
tween rescue PCI and conservative manage-
ment, the rate of reinfarction within 6 months
was significantly lower in the rescue PCI group
(relative risk 0.47, 95% confidence interval
0.26-0.84). Unplanned revascularization at 6
to 12 months was lower in the rescue PCI
group (relative risk 0.55, 95% confidence in-
terval 0.38-0.78). The meta-analysis also
showed lower mortality at 6 months (relative
risk 0.71, 95% confidence interval 0.44-1.13)
and lower rate of heart failure at 6 months
(relative risk 0.78, 95% confidence interval
0.56-1.09) in the rescue PCI group, but with
wide confidence intervals, translating to 57
fewer deaths per 1000 patients (95% confi-
dence interval: from 69 fewer to 16 more) and
44 fewer heart failures per 1000 patients (95%
confidence interval: from 88 fewer to 18
more). The panel concluded that the antici-
pated desirable effects of rescue PCI are
probably large compared to conservative
therapy.
The comparison between repeat fibrinolysis
and conservative management suggested
lower mortality at 6 weeks in the repeat fibri-
nolysis group (relative risk 0.28, 95% confi-
dence interval 0.10-0.81). The meta-analysis
for the mortality outcome included 2 studies
with a total of 127 patients (64 in the repeat
fibrinolysis arm and 63 in the conservative
arm), and the result appears to be driven by
events in the one study with an unexpectedly
high mortality (29%) in the control group110.
Another RCT, the REACT (Rescue Angioplasty
Versus Conservative Treatment or Repeat Fi-
brinolysis) Trial recruited 142 patients to re-
peat fibrinolysis and 141 to conservative ther-
apy, and reported mortality as time to event ,
with no difference in outcomes between the 2
groups including in longer term follow-up of
patients (median of 4.4 years of follow up).
Mortality at 6 months was 12.7% in repeat
22
Management of STEMI
fibrinolysis group and 12.8% in the conserva-
tive group and mortality at 4.4 years was
22.3% in the repeat fibrinolysis group and
22.4% in the conservative group. Repeat fibri-
nolysis did show a reduction in reinfarction at
6 months, heart failure at 6 months, or un-
planned revascularization before discharge.
The panel concluded that the desirable effects
of repeat fibrinolysis are probably not large
relative to the undesirable effects when com-
pared to conservative management.
Only one trial evaluated rescue PCI versus re-
peat fibrinolysis and assessing outcomes of
heart failure (relative risk 0.69, 95% confi-
dence interval 0.27-1.76), stroke (relative risk
2.96, 95% confidence interval 0.31-28.10), and
major bleeding (relative risk 0.56, 95% confi-
dence interval 0.17-1.88), with overall low
quality of evidence and uncertainty in the es-
timates of effects.
Harms of the Option: Rescue PCI was not as-
sociated with reported adverse events in the-
se trials. In the one study 110 of repeat fibri-
nolysis compared to conservative manage-
ment, unexpectedly, the rate of unplanned
revascularization was higher in the repeat fi-
brinolysis group. There was uncertainty about
the estimates of effects for the major bleed-
ing outcome with wide confidence intervals
when comparing repeat fibrinolysis versus
conservative management (relative risk 1.33,
95% confidence interval 0.47-3.74) and rescue
PCI versus repeat fibrinolysis (relative risk
0.56, 95% confidence interval 0.17-1.88). As
an important note, the panel noted that the
risk of bleeding would be much higher if using
streptokinase versus for example tissue plas-
minogen activator (tPA) or tenecteplase
(TNKase).
Resource Use: When compared to repeat fi-
brinolysis and conservative management, res-
cue PCI may require significant resources that
include the high cost of the procedure as well
as cost of transfer of the patient, which will
vary by geographical region across the KSA.
Although resources required are not small,
the incremental cost of rescue PCI was con-
sidered probably small relative to the benefit
as there is a net benefit for patients, with
lower likelihood of future events requiring
additional resource use for treatment. The
panel similarly noted the increased resource
use with repeat fibrinolysis, particularly con-
sidering the high cost of tPA and TNKase (es-
timated at 5000 SAR), and incremental cost
that is probably not small relative to the net
benefit as a result of probably no large benefit
shown in the analysis for repeat fibrinolysis.
Impact on Health Equity:
The panel noted that the option of rescue PCI
would increase health inequities in the KSA
setting, as outlined in the previous questions,
because of lack of universal access to PCI ser-
vices, particularly in peripheral geographic
areas. Patients would be treated differentially
depending on geographical location, with
some patients still denied access to the pro-
cedure. Repeat fibrinolysis may similarly in-
crease health inequity due to the high cost of
the drugs.
Acceptability: Rescue PCI was viewed as ac-
ceptable to key stakeholders including clini-
cians. Repeat fibrinolysis was viewed as prob-
ably not acceptable to key stakeholders as the
panel noted that most clinicians would not
provide repeat fibrinolysis.
Feasibility: Given current levels of access to
PCI services, rescue PCI may be difficult to
implement universally. Patients require trans-
fer to a PCI capable facility. The option may
not be feasible, particularly in geographical
areas in the KSA lacking PCI-capable facilities.
There are, however, geographical locations
where rescue PCI is already routinely per-
formed. The option of repeat fibrinolysis was
viewed as probably feasible, given availability
of tPA and TNKase.
Balance between desirable and undesirable
consequences: The desirable consequences of
rescue PCI probably outweigh undesirable
consequences when compared to both con-
servative management and repeat fibrinolysis
for patients with STEMI who fail to reperfuse
23
Management of STEMI
after fibrinolytic therapy. For repeat fibrinoly-
sis, the benefit is less clear based on limited
data, and repeat fibrinolysis should not in-
volve repeat administration of streptokinase
due to risk of adverse events and higher risk
of bleeding. Implementation of rescue PCI as
the treatment option for patients who fail to
reperfuse after fibrinolytic therapy requires
that feasibility issues around the lack of uni-
versal access to PCI services be addressed in
the KSA setting. The strength of recommenda-
tion is conditional due to uncertainty about
the feasibility, impact on health inequity, and
low quality of evidence.
Recommendations 8, 9, 10:
The panel suggests rescue PCI over conserva-
tive management (conditional recommenda-
tion, low quality evidence) and suggests res-
cue PCI over repeated fibrinolysis (condi-
tional recommendation, low quality evi-
dence) in patients with STEMI who failed to
reperfuse after fibrinolytic therapy. The pan-
el suggests not offering repeated fibrinolysis
in patients with STEMI who fail to reper-
fuse after fibrinolytic therapy (conditional
recommendation, low quality evidence).
Remarks:
When there is no available immedi-
ate urgent access for the patient at
a catheterization lab for the rescue
PCI procedure, treating clinicians
should determine with a lab if ac-
cess to rescue PCI can become
available for such patients.
There should not be a repeated
administration of streptokinase.
The risk of adverse events with re-
peat administration of streptoki-
nase is higher than the benefit.
Implementation Considerations and Monitor-
ing: In order to implement the recommenda-
tion for rescue PCI the feasibility issues re-
garding lack of universal access to PCI services
in specific geographical regions of the KSA
need to be addressed.
Research possibilities: The panel suggests fu-
ture research that will inform the implemen-
tation issues including a registry study to pro-
vide information regarding the number of pa-
tients eligible for rescue PCI who currently do
not receive rescue PCI. Keeping track of pa-
tients who do not have access to PCI services
and do not get treatment is intended to pro-
vide support for policymakers to improve ac-
cess across the KSA.
Question 9: Should routine early angiography
versus routine deferred or selective angi-
ography be used for STEMI successfully
treated by fibrinolysis?
Background: STEMI is usually caused by
thrombotic occlusion of a major coronary ar-
tery. Fibrinolytic therapy restores flow in the
coronary artery by lysing the thrombus lead-
ing to preserved myocardial function and de-
creased mortality. Complete reperfusion with
normal flow in the infarct related artery is
found only in half the patients who receive
fibrinolytic therapy. Following clinically suc-
cessful thrombolysis there may be residual
coronary stenosis at the site of the lesion
which may predispose to worsening coronary
stenosis and clinical events. Additionally pa-
tients with STEMI frequently have multi vessel
disease which may be responsible for symp-
toms and clinical events.
To evaluate the coronary anatomy and pre-
scribe the most appropriate mode of treat-
ment for patients with STEMI who are treated
with fibrinolysis, coronary angiography may
be recommended. The role and optimal tim-
ing of angiography has been studied in clinical
trials. This question addresses whether rou-
tine early versus routine deferred or selective
angiography should be used for management
of patients with STEMI successfully treated by
fibrinolysis.
Summary of Findings: The previously pub-
lished NICE systematic review identified 8
publications 113-120 relevant to this question.
Our literature search update identified one
24
Management of STEMI
additional study.121 The overall quality of evi-
dence was judged as moderate on the basis of
the reinfarction at 6 to 12 months outcome
and the estimates of effects for all critical out-
comes being in the same direction in favour of
early angiography.
Benefits of the Option: There was a large re-
duction in reinfarction at 6 to 12 months (rel-
ative risk 0.58, 95% confidence interval 0.41-
0.83) in patients receiving routine early angi-
ography, with an absolute effect of 28 fewer
patients with reinfarction per 1000 patients
(95% confidence interval; from 11 fewer to 39
fewer). The relative risk for mortality at 6 to
12 months with early angiography was 0.88
with a wide 95% confidence interval from 0.61
to 1.27, translating to 6 fewer deaths per
1000 patients (95% confidence interval: from
19 fewer to 13 more). There was also a reduc-
tion in recurrent ischemia at 6-12 months
(relative risk 0.52, 95% confidence interval
0.41-0.66) and unplanned revascularization
(relative risk 0.33, 95% confidence interval
0.25-0.44) with early angiography when com-
pared to the selective or deferred angi-
ography. Based on one study 118, the length of
hospital stay was also lower in the routine
angiography group (mean difference of 3.4
fewer days, 95% confidence interval of 2.41
fewer days to 4.39 fewer days)
Harms of the Option: There were no harms
identified for early angiography based on the
outcomes reported in these trials.
Resource Use: One pilot trial 122 was identified
in the literature search that performed a cost-
analysis comparing routine early angiography
versus a conservative strategy with risk strati-
fication based on stress myocardial perfusion
imaging. The cost analysis including total hos-
pital costs, costs of therapy, subsequent hos-
pitalization, subsequent noninvasive tests, or
repeat revascularization showed overall high-
er cost for routine early angiography versus
the conservative strategy at 6-month follow-
up with a cost of $4953.5 ± 3108.5 versus
$2764.6 ± 2636.7, respectively. The previously
published NICE systematic review included
one published cost-utility analysis 115,116 re-
porting an incremental cost-effectiveness ra-
tio (ICER) of £62,648 per QALY (quality-
adjusted life-year) gained for routine early
angiography compared to routine deferred
angiography (angiography where clinically
indicated or otherwise within 2 weeks of hos-
pital discharge) following STEMI successfully
treated by fibrinolysis. The cost-utility analysis
had two important limitations of high cost of
transfer due to helicopter ambulance costs as
well as a study population mortality rate low-
er than the general STEMI population poten-
tially underestimating benefits of early angi-
ography.
For the KSA setting, the incremental cost was
considered probably small relative to the net
benefits, given probably large benefit, and
resources required for routine early angi-
ography and transfer. Compared to the evi-
dence reviewed the panel considered that the
cost per QALY in the KSA would be lower.
Acceptability and Feasibility: The option of
early angiography was viewed as acceptable
to all key stakeholders. The availability of
catheterization lab time during the index hos-
pitalization for early angiography may be diffi-
cult in busy catheterization labs, and patients
treated in hospitals without a catheterization
lab would require transfer to a lab. Given the
issues of lack of universal access to catheteri-
zation labs in the KSA setting that were dis-
cussed in the previous questions, with the
panel noting that approximately 25% of the
population in the KSA does not have good ac-
cess to a catheterization lab, the option of
early angiography may not be feasible for all
patients. For patients in geographical regions
with access to catheterization labs the option
would be feasible.
Balance between desirable and undesirable
consequences: The desirable consequences of
routine early angiography compared to de-
ferred or selective angiography probably out-
weigh the undesirable consequences. A high
weight was placed on the benefit of early an-
giography on patient important outcomes and
25
Management of STEMI
in consideration of the feasibility issues in the
KSA setting the strength of recommendation
is conditional.
Recommendation 11:
The panel suggests routine early angiography
over routine deferred or selective angi-
ography in patients with STEMI successfully
treated by fibrinolysis. (conditional recom-
mendation, moderate quality evidence)
Implementation Considerations and Monitor-
ing: As outlined in questions 7 and 8 above,
implementation of this recommendation re-
quires addressing the feasibility issues regard-
ing lack of universal access to catheterization
labs, particularly in geographical regions pe-
ripheral to the urban centres in the KSA that
currently have catheterization labs.
Overall Research Priorities Identified for the
KSA
In formulating the above recommendations
the panel considered research priorities for
the KSA healthcare setting with respect to the
treatment of patients with STEMI. As dis-
cussed in the context of the recommenda-
tions made, current issues for the manage-
ment of patients with STEMI in the KSA center
around poorly developed emergency medical
services, resulting in delays in presentation to
hospitals and difficulties with transport and
transfer or patients, and lack of universal ac-
cess to catheterization labs with PCI services
for a significant portion of the population,
specifically in regions peripheral to urban cen-
tres. The feasibility issues have a particularly
strong impact on specific cases and groups of
patients receiving the most appropriate
treatment such as those who have failed to be
treated successfully with fibrinolytic therapy
(i.e. question 8), those who have been suc-
cessfully treated with fibrinolytic therapy (i.e.
question 9), and those who have suffered out-
of-hospital cardiac arrest (i.e. question 6) or
cardiogenic shock (i.e. question 5).
The main research priority outlined by the
panel involves conducting audits and high
quality registry studies with representation of
all geographical regions, which the panel had
identified as a potential limitation of existing
registry studies, to assess the current state of
practice and patients’ outcomes in the KSA
healthcare setting. The registry studies would
provide information about the number of pa-
tients eligible for PCI who currently do not
receive treatment with PCI (i.e. question 9),
and address queries previously outlined such
as how many patients with cardiac arrest ar-
rive to hospitals and are treated in the cathe-
terization lab and what their outcomes are
(i.e. question 6). The suggested research is
intended to inform policymakers to address
the implementation issues outlined with each
of the recommendations and to develop a
plan for improved and coordinated access to
the treatments that are most beneficial for
patients with STEMI.
26
Management of STEMI
References
1. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJL. Global and regional burden of disease
and risk factors, 2001: systematic analysis of population health data. The Lancet;367:1747-57.
2. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with
myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet
2004;364:937-52.
3. Alhabib KF, Hersi A, Alfaleh H, et al. Baseline characteristics, management practices, and in-
hospital outcomes of patients with acute