ESC Guidelines for the management of acute
coronary syndromes in patients presenting
without persistent ST-segment elevation
Chairpersons
Christian W. Hamm
Medical Clinic I
University Hospital Giessen
& Kerckhoff Heart and Thorax Center
Bad Nauheim,
Nauheim, Germany
JeanJean-Pierre Bassand
Department of Cardiology
University Hospital Jean Minjoz
Besançon,
Besançon, France
Members of the Task Force
Christian W. Hamm (Chairperson) (Germany),
Jean-Pierre Bassand (Chairperson), (France),
Stefan Agewall (Norway), Jeroen Bax (The Netherlands), Eric Boersma
(The Netherlands), Hector Bueno (Spain), Pio Caso (Italy), Dariusz Dudek (Poland),
Stephan Gielen (Germany), Kurt Huber (Austria), Magnus Ohman (USA), Mark C.
Petrie (UK), Frank Sonntag (Germany), Miguel Sousa Uva (Portugal), Robert F.
Storey (UK), William Wijns (Belgium), Doron Zahger (Israel).
Disclosures
Honoraria/Consulting/Speakers bureau
Astra Zeneca
Bayer
Eli Lilly
GSK
Iroko
MSD Shering Plough
Sanofi Aventis
European Heart Journal
Advance Access published August 26, 2011
European Heart Journal Advance Access published June 14, 2007
ESC Guidelines for the Management of NSTE-ACS (6)
• Diagnostic
What is new?
• High-sensitive troponin introduced
• Echocardiography standard
• Coronary CT for rule-out in low/intermediate
risk patients
• Risk Stratification
• 3-hour fast rule-out protocol
• Bleeding risk score (CRUSADE)
• Medical Treatment
• Ticagrelor and prasugrel introduced
• Revascularisation
• Timing of revascularisation
Recommendations for diagnosis and risk stratification 1
Mortality in hospital and at 6 months according to the
GRACE risk score
CRUSADE score of in-Hospital major bleeding
www.crusadebleedingscore.org
Risk of major bleeding across the spectrum of CRUSADE bleeding score
Recommendations for diagnosis and risk stratification 2
Recommendations for diagnosis and risk stratification 1
Rapid rule-out of ACS with high-sensitivity troponin.
HsTroponin I
Assay and Early
Diagnosis of MI
Keller T JAMA 2011; 306:2684
Hs Troponin I assay at 99 percentile cut-off
At 3 hours:
Sensitivity is 98.2%
NPV is 99.4%
Sensitive Troponin I Assay in ACS
Mills JAMA 2011; 305:1210
Implications of lowering threshold of plasma troponin
concentration in diagnosis of myocardial infarction:
cohort study
Mills BMJ 2012;344:e1533 doi: 10.1136/bmj.e1533
Implications of lowering threshold of plasma troponin
concentration in diagnosis of myocardial infarction:
cohort study
Mills BMJ 2012;344:e1533 doi: 10.1136/bmj.e1533
Implications of lowering threshold of plasma troponin
concentration in diagnosis of myocardial infarction:
cohort study
Mills BMJ 2012;344:e1533 doi: 10.1136/bmj.e1533
Keller T N Engl J Med 2009; 361:868
Keller T N Engl J Med 2009; 361:868
Troponin elevation
Possible non-acute coronary
syndrome causes
Cardiac and non-cardiac conditions that can mimic ACS
• Diagnostic
What is new?
• High-sensitive troponin introduced
• Echocardiography standard
• Coronary CT for rule-out in low/intermediate
risk patients
• Risk Stratification
• 3-hour fast rule-out protocol
• Bleeding risk score (CRUSADE)
• Medical Treatment
• Ticagrelor and prasugrel introduced
• Revascularisation
• Timing of revascularisation
Aspirin
Class
25
Level
P2Y12 Inhibitors
P2Y12 inhibitor recommendations 1
27
Class
Level
Class
Level
P2Y12 inhibitor recommendations 2
Class
28
Level
Cumulative incidence (%)
PLATO: time to first primary efficacy
event (composite of CV death, MI or stroke)
13
12
11
10
9
8
7
6
5
4
3
2
1
0
No. at risk
Ticagrelor
Clopidogrel
11.7
Clopidogrel
9.8
Ticagrelor
HR 0.84 (95% CI 0.77–0.92), p=0.0003
0
60
120
180
Days after randomisation
9,333
9,291
8,628
8,521
8,460
8,362
8,219
8,124
Curves are Kaplan-Meier rates, HR = hazard ratio; CI = confidence interval
240
6,743
6,743
300
5,161
5,096
360
4,147
4,047
Secondary efficacy endpoints over time
Cardiovascular death
Myocardial infarction
7
6
4
3
2
1
HR 0.84 (95% CI 0.75–0.95), p=0.005
0
0
60
120
180
240
300
360
Clopidogrel
5
Ticagrelor
Cumulative incidence (%)
Cumulative incidence (%)
6
5.8
5
No. at risk
7
6.9
Clopidogrel
5.1
4.0
4
Ticagrelor
3
2
1
HR 0.79 (95% CI 0.69–0.91), p=0.001
0
0
60
120
180
240
300
360
Days after randomisation
Days after randomisation
9,333
8,678
8,520
8,279
6,796
5,210
4,191
9,333
8,294
8,822
8,626
7119
5,482
4,419
Clopidogrel 9,291
8,560
8,405
8,177
6,703
5,136
4,109
9,291
8,865
8,780
8,589
7079
5,441
4,364
Ticagrelor
Ticagrelor
Class
31
Level
TRITON-TIMI study
TRITONBalance of Efficacy and Safety
15
138
events
Clopidogrel
12.1 HR 0.81
(0.73-0.90)
P=0.0004
9.9
NNT = 46
CV Death / MI / Stroke
Endpoint (%)
10
Prasugrel
5
TIMI Major
NonCABG Bleeds
35
events
Prasugrel
Clopidogrel
2.4 HR 1.32
1.8 (1.03-1.68)
P=0.03
0
0 30 60 90
180
Days
270
360
450
NNH = 167
Prasugrel
Class
33
Level
Clopidogrel dosing
34
Class
Level
Class
Level
Class
Level
Clopidogrel response variability
35
Class
Level
Class
Level
GP IIb/IIIa receptor inhibitor
36
Class
Level
Class
Level
ISAR-REACT 2: Outcomes according to Tn level
Death/MI/UTVR, %
20
Troponin-Positive: RR=0.71 [0.54-0.95]
15
Abciximab vs. Placebo
10
Troponin-Negative: RR=0.99 [0.56-1.76]
5
0
0
Kastrati A et al. JAMA 2006
5
10
15
20
25
30
Days after randomization
ACUITY Timing
Routine Upstream IIb/IIIa vs. Deferred PCI IIb/IIIa
30 day events (%)
Routine Upstream IIb/IIIa (N=4605)
PNI <0.0001
PSup = 0.93
Deferred PCI IIb/IIIa (n=4602)
PNI = 0.044
PSup = 0.13
PNI < 0.0001
PSup = 0.009
11,7% 11,7%
7,1%
Net clinical
outcome
Stone, G. W. et al. JAMA 2007;297:591-602
7,9%
Ischemic
composite
6,1%
4,9%
Major bleeding
EARLY ACS
Delayed provisional vs routine early eptifibatide
Death, MI, recurrent ischaemia or thrombotic bailout
Primary endpoint
15
10.0%
10
Delayed provisional
eptifibatide
9.3%
P=0.23
5
(stratified for intended early
clopidogrel use)
Routine early
eptifibatide
0
0
8
16
24
32
40
48
56
64
72
Time Since Randomization, h
RIUR = recurrent ischemia requiring urgent revascularization, TBO = thrombotic bailout.
Giugliano RP, et al. NEJM. 2009;360:2176-90.
80
88
96
PLATO: major bleeding according
to use of GPIIb
GPIIb//IIIa antagonist during
hospitalisation
40
Upstream GP IIb/IIIa receptor inhibitor
41
Class
Level
Class
Level
Class
Level
Bivalirudin vs GPIIb/
GPIIb/IIIa antagonists
Class
42
Level
Anticoagulants
43
Class
Level
Class
Level
0.01 0.02 0.03 0.04 0.05 0.06
HR 1.01
95% CI 0.90-1.13
Enoxaparin
Fondaparinux
0.0
Cumulative Hazard
Death/MI/RI: Day 9
0
1
2
3
4
5
Days
6
7
8
9
Enoxaparin
0.02
0.03
HR 0.53
95% CI 0.45-0.62
P<<0.00001
0.01
Fondaparinux
0.0
Cumulative Hazard
0.04
Major Bleeding: 9 Days
0
1
2
3
4
5
Days
6
7
8
9
Mortality: Day 30
0.02
Fondaparinux
0.01
HR 0.83
95% CI 0.71-0.97
P=0.022
0.0
Cumulative Hazard
0.03
Enoxaparin
0
3
6
9
12
15
Days
18
21
24
27
30
Outcomes to 30 days
Major Bleed at 30 days
0.05
0.04
0.04
Low dose 2.2% vs. Standard dose 1.8%,
HR 1.20 (95% CI 0.64-2.23, p=0.57)
0.03
0.03
Low dose 4.5% vs. Standard dose 2.9%
HR 1.56 (95% CI 0.98-2.48, p=0.06)
0.02
0.02
0.01
0.01
Standard Dose
Low Dose
Standard Dose
Low Dose
0.0
0.0
0
3
6
9
12
15
18
21
24
27
0
30
3
6
9
12
No. at Risk
No. at Risk
Days
Standard Dose 1002
Low Dose
Death/MI/TVR at 30 days
0.05
1024
986
1002
981
1001
980
998
980
997
15
18
21
24
27
30
Days
978
Standard Dose 1002
980
975
975
974
971
994
Low Dose
997
988
982
981
978
1024
Subgroup analysis showed consistent results for primary outcome
and for death/MI/TVR for pre-specified subgroups of: Age, Sex,
GP IIb/IIIa, BMI, CrCl, Arterial access site
Fondaparinux
48
Class
Level
Class
Level
Heparins
Class
Level
Class
Level
Use of
antithrombotic drugs
in chronic kidney
disease
50
Recommendations for oral antiplatelet agents 1
PLATO
TRITON-TIMI 38
CH9
Recommendations for GP IIb/IIIa receptor inhibitors
Dia 52
CH9
Tabelle teilen, nebeneinander auf 1 Seite
Prof. Dr. Christian Hamm; 21-8-2011
Recommendations for anticoagulants
Decision-making algorithm in ACS
Recommendations for invasive evaluation and revascularization
Criteria for high risk with indication for
invasive management
“Management Strategy”
of NSTE - ACS
Management of NSTE - ACS
• Step 1: Initial evaluation
• Step 2: Diagnosis validation and
risk assessment
• Step 3: Invasive strategy
• Step 4: Revascularisation modality
• Step 5: Hospital discharge and
post-discharge
Initial therapeutic measures
Checklist of treatments when an ACS diagnosis appears likely
Checklist of antithrombotic treatments prior to PCI
Measures checked at discharge
Take Home messages
• NSTE-ACS is a frequent cause of hospitalization
Heterogenous population as regards risk
• Diagnostics
•
•
•
•
Clinical presentation, ECG, troponin
High-sensitive troponin introduced
Echocardiography for everybody
Coronary CT for rule-out in low/intermediate risk patients
• Risk Stratification
• 3-hour fast rule-out protocol based on hs-troponin
• Ischaemic risk (GRACE score )
• Bleeding risk (CRUSADE score )
Take Home messages (continued 1)
• First line antithrombotic treatment
• Ticagrelor and prasugrel recently introduced
• Revascularisation
• Timing of revascularisation customized according to risk
– Within 72 hours anyway, but
– Within 2 hours for very high risk patients (lifethreatening symptoms)
– Within 24 hours for patients with high risk criteria (GRACE score > 140,
troponin release, ST-T changes)
• Non invasive evaluation for low risk patients
Take Home messages (continued 2)
• Special populations and situations
• Diabetes, elderly, women, CKD, anaemia.....
• Bleeding complications ...
• Long term secondary prevention
• Secondary prevention programmes
• Lifestyle
• Drug therapy
Risk of major bleeding across the spectrum of CRUSADE bleeding score
Ten Take home messages
1 - NSTE-ACS is a frequent cause of
hospitalization
2 - Heterogenous population as regards risk
3 - Diagnostic
•
•
•
•
•
Clinical presentation
ECG
(High-)sensitive troponin
Echocardiography standard for all
Coronary CT for rule-out in low/intermediate risk patients
4 - Risk Stratification
•
•
3-hour fast rule-out protocol based on hs-troponin
Ischaemic risk (GRACE score )
•
Bleeding risk (CRUSADE score )
Ten Take home messages
5 - Antischaemic Therapy
6 - Antiplatelet treatment
•
•
•
•
•
Aspirin lifelong for all, plus
Ticagrelor (12 months) or
Prasugrel (only prior PCI)
Clopidogrel , if ticagrelor and prasugrel not available
Glycoprotein IIb/IIIa in high risk patients, but not
routinely upstream
7 - Anticoagulation
•
•
•
Fondaparinux best benefit/ risk profile (add UFH if PCI)
Enoxaparin, other low molecular weight heparins or
unfractionated heparin are less recommended options
Bivalirudin in high risk bleeding as alternative to GP
IIb/IIIa + UFH in patients undergoing PCI
Ten Take home messages
8 - Revascularisation
•
Timing of revascularisation customized according to risk
–
–
–
•
Within 72 hours all patients at risk, but
Within 2 hours for very high risk patients (lifethreatening
symptoms)
Within 24 hours for patients with high risk criteria (GRACE
score > 140, troponin release, ST-T changes)
Non invasive evaluation for low risk patients
9 - Special populations and situations
•
Special attention to diabetes, elderly, women, CKD,
anaemia.
•
Adjust medication doses according to renal function
10 - Long term management, secondary
prevention
Thank you !