1. 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

2. From plaque formation to progression to clinical manifestations
STABLE
No symptoms
Silent ischemia
Stable angina
Slow
Risk factor
Atherosclerosis
progression
UNSTABLE
Unstable angina
NSTEMI
STEMI
Sudden cardiac death
Accelerated Progression
Atherothrombosis

3. Distribution of ACS type in Kuwait Discharge diagnosis 2534 patients

5. Gulf COAST 2012 Kuwait population
STEMI (288)
n (%)
Age (Mean ±SD)
56.7±13.3
Female
61 (21)
Hypertension
145 (50)
Diabetes
152 (53)
Smoking
164 (57)
Prior MI
41 (14)
Prior PCI
25 (9)
Prior CABG
7 (2)
Prior TIA
Prior stroke
19 (7)

6. Pooled analysis of the short-term results from 23 randomized trials comparing primary PCI and fibrinolytic therapy in 7739 patients
Figure 1. Pooled analysis of the short-term results from 23 randomized trials comparing primary PCI and fibrinolytic therapy in 7739 total patients. Data from Reference 13. Data vary slightly from Reference 13 because of presentation of relative risks (RRs) rather than ORs.
Stone G. Circulation 2008;118:

7. 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 I A
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. B
Steg et al, EHJ 2012;33:

8. Periprocedural antithrombotic medications in primary PCI
Recommendations
Class
Level
Antiplatelet therapy
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: A
Prasugrel in clopidogrel-naive patients, if no history of prior stroke/TIA, age <75 years.
Ticagrelor
Clopidogrel, preferably when prasugrel or ticagrelor are either not available or contraindicated C
Steg et al, EHJ 2012;33:

9. Fibrinolytic therapy Recommendations Class Level I A IIa B
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 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
A fibrin – specific agent (tenecteplase, alteplase, reteplase) is recommended ( over non – fibrin specific agents)
Oral or i.v. aspirin must be administered
Clopidogrel is indicated in addition to aspirin
Steg et al, EHJ 2012;33:

10. PCI post lysis Recommendations Class Level
Transfer to a PCI capable center following fibrinolysis
Is indicated in all patients after fibrinolysis I A
Interventions following fibrinolysis
Rescue PCI is indicated immediately when fibrinolysis has failed (< 50% ST- segment resolution at 60 min).
Emergency PCI is indicated in the case of recurrent ischemia or evidence of reocclusion after initial successful fibrinolysis. B
Steg et al, EHJ 2012;33:

11. 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
Yes No
Preferably ≤ 90 min
(≤ 60 min in early presenters)
Preferably
≤ 30 min
Rescue PCI
Immediate transfer to PCI center
Immediately No
Successful fibrinolysis
Immediate fibrinolysis
Yes
Preferably
3-24 h
Coronary angiography
Steg et al, EHJ 2012;33:

12. 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
From the previous algorithm you can see that there are some stages/timelines that are highlighted.
Steg et al, EHJ 2012;33:

13. Components of delay in STEMI
Symptom onset
FMC
Diagnosis
Reperfusion therapy
≤ 10 min
Patient delay
………..………………....
………..………………
………..………………...
System delay
………..………………
Time to reperfusion therapy
Wire passage in culprit artery (primary PCI)
Start of lysis
Steg et al, EHJ 2012;33:

14. Reperfusion in eligible patients Per country
Bahrain
(n= 119)
UAE
(n= 129)
Oman
(n= 315)
Kuwait
(n=259) 29 40
0.3 6
PPCI (%) 58 49 92 86
Lysis (%) 13 11
7.7 8
Shortfall (%)

15. Reperfusion in eligible patients Kuwait
Rest of Hospital
(n= 203)
Adan Hospital
(n=56) 27
PPCI (%) 93 64
Lysis (%) 7 9
Shortfall (%)

16. Was reperfusion administered in time?

17. Reperfusion Timeline Thrombolysis in Kuwait
Rest of Hospital
(n= 188)
Adan Hospital
(n=37)
Thrombolysis 41 34
Median D2NT (min) 36 43
D2NT ≤30 min (%)

18. Primary PCI experience Adan Hospital November 13 – December 30, 2013
Distribution of timeline

19. 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%

20. Primary PCI experience Mubarak Alkabeer Hospital
November 13 – December 30, 2013
Held off for two weeks in the middle
Distribution of timeline

21. Adan (33 patients) MKH (24 patients)
Primary PCI experience
MKH vs. Adan Hospital
November 13 – December 30, 2013
Distribution of timeline (values in mean)
Adan (33 patients)
MKH (24 patients)
Symptom onset to ER arrival
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%
Door to balloon ≤90 minutes
85%
15%
Door to balloon ≤120 minutes
97%
65%

22. Components of delay in STEMI
Symptom onset
FMC
Diagnosis
Reperfusion therapy
≤ 10 min
Patient delay
………..………………....
………..………………
………..………………...
System delay
………..………………
Time to reperfusion therapy
Wire passage in culprit artery (primary PCI)
Start of lysis
Steg et al, EHJ 2012;33:

23. Door to balloon in hospitals with and without cath labs in Kuwait
Adan Hospital
Cardiology response time
Door to ECG
ECG to Cardiology
Door to balloon 7 9 4 64
Mubarak AlKabeer Hospital
Door to ECG
ECG to Cardiology
Cardiology response time
Door to balloon
Ambulance notification
Ambulance response
Ambulance trip time 18 20 3 5 13 30
111

24. In-hospital cardiac catheterization

25. 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
Yes No
Preferably ≤ 90 min
(≤ 60 min in early presenters)
Preferably
≤ 30 min
Rescue PCI
Immediate transfer to PCI center
Immediately No
Successful fibrinolysis
Immediate fibrinolysis
Yes
Preferably
3-24 h
Coronary angiography
Steg et al, EHJ 2012;33:

26. PCI post lysis Recommendations Class Level
Transfer to a PCI capable center following fibrinolysis
Is indicated in all patient after fibrinolysis I A
Interventions following fibrinolysis
Rescue PCI is indicated immediately when fibrinolysis has failed (< 50% ST- segment resolution at 60 min).
Emergency PCI is indicated in the case of recurrent ischemia or evidence of reocclusion after initial successful fibrinolysis. B
Steg et al, EHJ 2012;33:

27. Kuwait Gulf COAST population
Rates of inhospital cath for STEMI patients
STEMI (288)
n (%)
Cath during hospital stay
120 (42)
Adan Hospital
61 (87)
The rest of hospitals
59 (27)
Hospital arrival to PCI at Adan, Mean±SD, Median (days)
0.86±1.2, 0.00
Hospital arrival to PCI excluding Adan, Mean±SD, Median (days)
4.4±3.5, 3

28. 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
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
Routine glucose-insulin-potassium infusion is not indicated
III A
Remember, STEMI management is not just about reperfusion therapy
Steg et al, EHJ 2012;33:

29. Routine therapies in the acute, subacute and long term phase of STEMI
Recommendations
Class
Level
Oral treatment with betablockers should be considered during hospital stay and continued thereafter in all STEMI patients without contraindications
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 C
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:

30. Routine therapies in the acute, subacute and long term phase of STEMI
Recommendations
Class
Level
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 I A
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 B
ACE inhibitor should be considered in all patients in the absence of contraindications
IIa
Aldosterone antagonists are indicated in patients with an ejection fraction ≤40% and heart failure or diabetes, provided no renal failure or hyperkalaemia
Steg et al, EHJ 2012;33:

31. Adherence to medical therapy

32. Gulf COAST STEMI/NSTEMI
2012
Gulf RACE
2007¹
EHS-ACS-II
2004²
NRMI-5 ³
Aspirin at arrival (%) 99 98 97 90
Aspirin prescribed at discharge (%) 91
Beta- blocker at discharge (%) 85 78 71 89
Statin at discharge (%) 84 80 82
Clopidogrel at discharge
for medically treated AMI patients (%) 67 57 63 -

33. From plaque formation to progression to clinical manifestations
STABLE
No symptoms
Silent ischemia
Stable angina
Slow
Risk factor
Atherosclerosis
progression
UNSTABLE
Unstable angina
NSTEMI
STEMI
Sudden cardiac death
Accelerated Progression
Atherothrombosis

35. Work up of ischemic chest pain
Admission
Working diagnosis
Acute Coronary Syndrome
Persistent
ST-elevation
ST/T– abnormalities
normal or undetermined ECG
ECG
troponin
rise/fall
troponin
normal
Bio-chemistry
Diagnosis
STEMI
NSTEMI Unstable
Angina
Hamm et al, EHJ 2011;32:

37. 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:

38. Gulf COAST Kuwait population
NSTEMI (574)
n (%)
Age (Mean ±SD)
61.7±12.3
Female
221 (39)
Hypertension
403 (70)
Diabetes
391 (68)
Smoking
177 (31)
Prior MI
208 (36)
Prior PCI
120 (21)
Prior CABG
45 (8)
Prior TIA
28 (5)
Prior stroke
57 (10)

39. Decision – making algorithm in ACS
1.Clinical Evaluation Diagnosis/Risk Assessment Coronary angiography
STEMI
reperfusion
urgent
< 120 min
Evaluation
Quality of chest pain.
Symptom - orientated physical examination.
Short history for the likelihood of CAD.
Electrocardiogram
(ST elevation?)
Validation
Response to antianginal treatment.
Biochemistry/troponin.
ECG
Echocardiogram.
Calculated risk score (GRACE)
Risk Criteria.
Optional: CT, MRI, scintigraphy.
ACS possible
early
<24h
<72h
No CAD
no/elective
Hamm et al, EHJ 2011;32:

40. Antithrombotic treatment in NSTE ACS
Targets for antithrombics
Antiplatelet
Anticoagulation
Tissue Factor
Collagen
Aspirin
Plasma clotting cascade
Fondaparinux
ADP
Clopidogrel
Prasugrel
Ticagrelor
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:

42. 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.