Updates in Acute Coronary Syndromes Management
Mohammad Zubaid, MB, ChB, FRCPC, FACC
Professor of Medicine, Kuwait University
Head, Division of Cardiology
Mubarak Alkabeer Hospital
Kuwait
The 1st Kuwait-North American update in Internal Medicine
4th Medical Scientific Conference – Mubarak Alkabeer Hospital
February 7, 2014 – Jumeirah hotel, Kuwait
From plaque formation to progression to clinical manifestations
Plaque formation
Risk factor
Clinical manifestations
Slow
progression
Atherosclerosis
Accelerated
Progression
Atherothrombosis
STABLE
 No symptoms
 Silent ischemia
 Stable angina




UNSTABLE
Unstable angina
NSTEMI
STEMI
Sudden cardiac death
Distribution of ACS type in Kuwait
Discharge diagnosis 2534 patients
Gulf COAST 2012
Kuwait population
Age (Mean ±SD)
Female
Hypertension
Diabetes
Smoking
Prior MI
Prior PCI
Prior CABG
Prior TIA
Prior stroke
STEMI (288)
n (%)
56.7±13.3
61 (21)
145 (50)
152 (53)
164 (57)
41 (14)
25 (9)
7 (2)
7 (2)
19 (7)
Pooled analysis of the short-term results from 23 randomized trials
comparing primary PCI and fibrinolytic therapy in 7739 patients
Stone G. Circulation 2008;118:538-551
Primary PCI
Recommendations
Class
Level
Indications for primary PCI
Primary PCI is the recommended reperfusion therapy
over fibrinolysis if performed by an experienced team
within 120 min of FMC
Primary PCI is indicated for patients with severe acute
heart failure or cardiogenic shock, unless the expected
PCI related delay is excessive and the patient presents
early after symptom onset.
I
A
I
B
Steg et al, EHJ 2012;33:2569-2619
Periprocedural antithrombotic medications
in primary PCI
Recommendations
Class
Level
Aspirin oral or i.v. (if unable to swallow) is recommended
I
B
An ADP- receptor blocker is recommended in addition to
aspirin.
Option are:
I
A
• Prasugrel in clopidogrel-naive patients, if no history of
prior stroke/TIA, age <75 years.
I
B
• Ticagrelor
I
B
• Clopidogrel, preferably when prasugrel or ticagrelor
are either not available or contraindicated
I
C
Antiplatelet therapy
Steg et al, EHJ 2012;33:2569-2619
Fibrinolytic therapy
Recommendations
Class
Level
I
A
In patient presenting early (<2 h after symptom onset ) with
large infarct and low bleeding risk, fibrinolysis should be
considered if time from FMC to balloon inflation is >90 min
IIa
B
If possible, fibrinolysis should start in the Prehospital setting
IIa
A
A fibrin – specific agent (tenecteplase, alteplase, reteplase) is
recommended ( over non – fibrin specific agents)
I
B
Oral or i.v. aspirin must be administered
I
B
Clopidogrel is indicated in addition to aspirin
I
A
Fibrinolytic therapy is recommended within 12 h of symptom
onset in patients without contraindications if primary PCI cannot
be performed by an experienced team within 120 min of FMC
Steg et al, EHJ 2012;33:2569-2619
PCI post lysis
Recommendations
Class
Level
I
A
Rescue PCI is indicated immediately when fibrinolysis has
failed (< 50% ST- segment resolution at 60 min).
I
A
Emergency PCI is indicated in the case of recurrent
ischemia or evidence of reocclusion after initial successful
fibrinolysis.
I
B
Transfer to a PCI capable center following fibrinolysis
Is indicated in all patients after fibrinolysis
Interventions following fibrinolysis
Steg et al, EHJ 2012;33:2569-2619
Prehospital and in-hospital management
Reperfusion stratergies within 24 h of FMC
STEMI diagnosis
Primary PCI capable center
EMS or non primary-PCI capable center
Preferably < 60 min
PCI possible <120 min?
Immediate transfer to PCI center
Primary - PCI
Rescue PCI
Immediately
Yes
Preferably ≤ 90 min
(≤ 60 min in early presenters)
Immediate transfer
to PCI center
No
Preferably
≤ 30 min
No
Yes
Successful fibrinolysis
Immediate fibrinolysis
Preferably
3-24 h
Coronary angiography
Steg et al, EHJ 2012;33:2569-2619
Important treatment goals
in the management of STEMI
Stages
Target
Preferred for FMC to ECG and diagnosis
≤ 10 min
Preferred for FMC to fibrinolysis (FMC to needle)
≤ 30 min
Preferred for FMC to primary PCI (door to balloon)
in primary PCI hospitals
≤ 60 min
Preferred for FMC to primary PCI in hospitals
without cath facility
≤ 90 min
(≤ 60 min if early presenter with large
area at risk) if this target cannot be
met, consider fibrinolysis
Acceptable for primary PCI rather than fibrinolysis
≤ 120 min
(≤ 90 min if early presenter with large
area at risk) if this target cannot be
met, consider fibrinolysis
Preferred for successful fibrinolysis to angiography
3-24 hours
Steg et al, EHJ 2012;33:2569-2619
Components of delay in STEMI
Symptom onset
FMC
Reperfusion therapy
System delay
Time to reperfusion therapy
Wire passage in culprit artery (primary PCI)
Steg et al, EHJ 2012;33:2569-2619
………..……………….................
≤ 10 min
………..………………...
………..………………....
………..……………….........
Patient delay
Diagnosis
Start of lysis
Reperfusion in eligible patients
Per country
Kuwait
Oman
UAE
Bahrain
(n=259)
(n= 315)
(n= 129)
(n= 119)
40
29
49
58
11
13
PPCI (%)
6
0.3
Lysis (%)
86
92
Shortfall (%)
8
7.7
Reperfusion in eligible patients
Kuwait
Adan Hospital
Rest of Hospital
(n=56)
(n= 203)
PPCI (%)
27
0
Lysis (%)
64
93
Shortfall (%)
9
7
Was reperfusion administered in time?
Reperfusion Timeline
Thrombolysis in Kuwait
Thrombolysis
Adan Hospital
Rest of Hospital
(n=37)
(n= 188)
Median D2NT (min)
34
41
D2NT ≤30 min (%)
43
36
Primary PCI experience
Adan Hospital
November 13 – December 30, 2013
Distribution of timeline
Primary PCI experience
Adan Hospital
November 13 – December 30, 2013
Distribution of timeline during and after normal working hours
During working hours
14 patients
After working hours
45 patients
Door to ECG
5
7
ECG to cardiology notification
11
6
Cardiology response time
4
3
Door to balloon time
51
62
Door to balloon ≤60 minutes
71%
53%
Door to balloon ≤90 minutes
93%
89%
Primary PCI experience
Mubarak Alkabeer Hospital
November 13 – December 30, 2013
Held off for two weeks in the middle
Distribution of timeline
Primary PCI experience
MKH vs. Adan Hospital
November 13 – December 30, 2013
Distribution of timeline (values in mean)
Adan (33 patients)
MKH (24 patients)
205
124
Door to ECG
7
18
ECG to cardiology notification
9
20
Cardiology response time
4
3
Door to balloon time
64
111
Door to balloon ≤60 minutes
48%
0
Door to balloon ≤90 minutes
85%
15%
Door to balloon ≤120 minutes
97%
65%
Symptom onset to ER arrival
Components of delay in STEMI
Symptom onset
FMC
Reperfusion therapy
System delay
Time to reperfusion therapy
Wire passage in culprit artery (primary PCI)
Steg et al, EHJ 2012;33:2569-2619
………..……………….................
≤ 10 min
………..………………...
………..………………....
………..……………….........
Patient delay
Diagnosis
Start of lysis
Door to balloon in hospitals with and without cath labs in Kuwait
Adan Hospital
ECG to
Cardiology
Door to ECG
Cardiology
response time
9
7
Door to balloon
64
4
Mubarak AlKabeer Hospital
Door to ECG
18
ECG to
Cardiology
20
Cardiology
response time
3
Door to balloon
5
Ambulance
notification
13
Ambulance
response
30
Ambulance
trip time
111
In-hospital cardiac catheterization
Prehospital and in-hospital management
Reperfusion stratergies within 24 h of FMC
STEMI diagnosis
Primary- PCI capable center
EMS or non primary-PCI capable center
Preferably < 60 min
PCI possible <120 min?
Immediate transfer to PCI center
Primary - PCI
Rescue PCI
Immediately
Yes
Preferably ≤ 90 min
(≤ 60 min in early presenters)
Immediate transfer
to PCI center
No
Preferably
≤ 30 min
No
Yes
Successful fibrinolysis
Immediate fibrinolysis
Preferably
3-24 h
Coronary angiography
Steg et al, EHJ 2012;33:2569-2619
PCI post lysis
Recommendations
Class
Level
I
A
Rescue PCI is indicated immediately when fibrinolysis has
failed (< 50% ST- segment resolution at 60 min).
I
A
Emergency PCI is indicated in the case of recurrent
ischemia or evidence of reocclusion after initial successful
fibrinolysis.
I
B
Transfer to a PCI capable center following fibrinolysis
Is indicated in all patient after fibrinolysis
Interventions following fibrinolysis
Steg et al, EHJ 2012;33:2569-2619
Kuwait Gulf COAST population
Rates of inhospital cath for STEMI patients
Cath during hospital stay
STEMI (288)
n (%)
120 (42)
Adan Hospital
61 (87)
The rest of hospitals
59 (27)
Hospital arrival to PCI at Adan, Mean±SD, Median (days)
Hospital arrival to PCI excluding Adan, Mean±SD, Median (days)
0.86±1.2, 0.00
4.4±3.5, 3
Management of hyperglycemia
in the acute phase of STEMI
Recommendations
Class
Level
Measurement of glycaemia is indicated at initial evaluation in all patients,
and should be repeated in patients with know diabetes or hyperglycemia
I
C
Plans for optimal outpatient glucose control and secondary prevention
must be determined in patients with diabetes before discharge
I
C
The goals of glucose control in the acute phase should be to
maintain glucose concentrations ≤11.0 mmol/L (200mg/dL) while
avoiding fall of glycaemia<5 mmol/L (<90mg/dL). In some patients,
this may require a dose-adjusted insulin infusion with monitoring of
glucose, as long as hypoglycemia is avoided
IIa
B
A measurement of fasting glucose and HbA1c and , in some cases, a
post- discharge oral glucose tolerance test should be considered in
patients with hyperglycemia but without a history of diabetes
IIa
B
Routine glucose-insulin-potassium infusion is not indicated
III
A
Steg et al, EHJ 2012;33:2569-2619
Routine therapies in the acute,
subacute and long term phase of STEMI
Recommendations
Class
Level
IIa
B
Oral treatment with betablockers is indicated in patients with heart
failure or LV dysfunction
I
A
A fasting lipid profile must be obtained in all STEMI patients, as
soon as possible after presentation
I
C
I
A
IIa
C
Oral treatment with betablockers should be considered during
hospital stay and continued thereafter in all STEMI patients
without contraindications
It is recommended to initiate or continue high dose statins early
after admission in all STEMI patients without contraindication or
history of intolerance, regardless of initial cholesterol values
Reassessment of LDL should be considered after 4-6 weeks to
ensure that a target value of ≤1.8 mmol/L (70 mg/dL) has been
reached
Steg et al, EHJ 2012;33:2569-2619
Routine therapies in the acute,
subacute and long term phase of STEMI
Recommendations
ACE Inhibitors are indicated starting within the first 24 h of
STEMI in patients with evidence of heart failure, LV systolic
dysfunction, diabetes or an anterior infarct
An ARB, preferably valsartan, is an alternative to ACE
inhibitors in patient with heart failure or LV systolic
dysfunction, particularly those who are intolerant to ACE
inhibitors
ACE inhibitor should be considered in all patients in the
absence of contraindications
Aldosterone antagonists are indicated in patients with an
ejection fraction ≤40% and heart failure or diabetes,
provided no renal failure or hyperkalaemia
Class
Level
I
A
I
B
IIa
A
I
B
Steg et al, EHJ 2012;33:2569-2619
Adherence to medical therapy
Gulf COAST
STEMI/NSTEMI
Gulf COAST
2012
Gulf RACE
2007¹
EHS-ACS-II
2004²
NRMI-5
2004-2006³
Aspirin at arrival (%)
99
98
97
90
Aspirin prescribed at discharge (%)
97
97
90
91
Beta- blocker at discharge (%)
85
78
71
89
Statin at discharge (%)
97
84
80
82
Clopidogrel at discharge
for medically treated AMI patients (%)
67
57
63
-
From plaque formation to progression to clinical manifestations
Plaque formation
Risk factor
Clinical manifestations
Slow
progression
Atherosclerosis
Accelerated
Progression
Atherothrombosis
STABLE
 No symptoms
 Silent ischemia
 Stable angina




UNSTABLE
Unstable angina
NSTEMI
STEMI
Sudden cardiac death
Work up of ischemic chest pain
Chest Pain
Admission
Working
diagnosis
ECG
Acute Coronary Syndrome
Persistent
ST-elevation
troponin
rise/fall
Bio-chemistry
Diagnosis
Hamm et al, EHJ 2011;32:2999-3054
ST/T–
abnormalities
STEMI
NSTEMI
normal or
undetermined
ECG
troponin
normal
Unstable
Angina
Criteria for high risk with indication
for invasive management
Primary
• Relevant rise or fall in troponin
• Dynamic ST- or T- wave changes (symptomatic or silent)
Secondary
•
•
•
•
•
•
•
Diabetes mellitus
Renal insufficiency (eGFR < 60 mL/min/1.73m2)
Reduced LV function (ejection fraction < 40 %)
Early post infarction angina
Recent PCI
Prior CABG
Intermediate to high GRACE risk score
Hamm et al, EHJ 2011;32:2999-3054
Gulf COAST
Kuwait population
Age (Mean ±SD)
Female
Hypertension
Diabetes
Smoking
Prior MI
Prior PCI
Prior CABG
Prior TIA
Prior stroke
NSTEMI (574)
n (%)
61.7±12.3
221 (39)
403 (70)
391 (68)
177 (31)
208 (36)
120 (21)
45 (8)
28 (5)
57 (10)
Decision – making algorithm in ACS
1.Clinical Evaluation
2. Diagnosis/Risk Assessment
STEMI
reperfusion
urgent
< 120 min
Evaluation
•
•
•
•
3. Coronary angiography
Validation
•
Quality of chest pain.
Symptom - orientated
physical examination.
Short history for the
likelihood of CAD.
Electrocardiogram
(ST elevation?)
ACS
possible
•
•
•
•
•
•
Response to antianginal
treatment.
Biochemistry/troponin.
ECG
Echocardiogram.
Calculated risk score
(GRACE)
Risk Criteria.
Optional: CT, MRI,
scintigraphy.
early
<24h
<72h
No CAD
no/elective
Hamm et al, EHJ 2011;32:2999-3054
Antithrombotic treatment in NSTE ACS
Targets for antithrombics
Anticoagulation
Tissue Factor
Collagen
Antiplatelet
Aspirin
Plasma clotting
cascade
Fondaparinux
ADP
Thromboxane A2
Prothrombin
LMWH
Heparin
AT
Factor
Xa
Conformational
activation of GPIIb/IIIa
AT
GPIIb/IIIa
inhibitors
Thrombin
Platelet
aggregation
Bivalirudin
Fibrinogen
Fibrin
Thrombus
Hamm et al, EHJ 2011;32:2999-3054
Clopidogrel
Prasugrel
Ticagrelor
Conclusions
 Management of ACS has evolved rapidly over the past few years.
 Early risk stratification and cardiac catheterization is a cornerstone in
ACS management.
 If we want to benefit our patients, it is important that we examine what we
do.
 Our ACS patients receive good medical therapy at discharge from
hospital.
 However, we rely heavily on lytic therapy for reperfusion in STEMI and it
is not administered in efficient timing to get the most benefit from it.
 In both STEMI and NSTE ACS, our use of cardiac catheterization falls
short of guidelines recommendations.