Akute Koronarsyndrome

12. Berner Notfall-Symposium, 17. Oktober 2013
Akute Koronarsyndrome
Risikostratifizierung, Netzwerkstrategie und
Medikamenten-Update
Stephan Windecker
Department of Cardiology
Swiss Cardiovascular Center and Clinical Trials Unit Bern
Bern University Hospital, Switzerland
ST-Elevation ACS
Non ST-Elevation ACS
Chest Pain
Admission
Working
diagnosis
ECG
Suspicion of Acute Coronary Syndrome
Persistent
ST –elevation
Biochemistry
Risk
stratification
ST/T –
Abnormalities
Undetermined ECG
Troponin
positive
Troponin
2 x Negative
High Risk
Diagnosis
STEMI
Treatment
Reperfusion
NSTEMI
Invasive
Normal or
Low Risk
Unstable Angina
Non-invasive
Risk
Stratification
in NSTE-ACS
Acute
Myocardial
Infarction
Update on
Prehospital
Medications
Patient and
System Delay
in STEMI
Relationship of Troponin Level
to Early Mortality in ACS
Antman EM et al. NEJM 1996;335:1342-49
Death by 42 days (%)
8
7.5
p <0.001
6
6
4
2
3.4
3.7
1.0-<2.0
2.0-<5.0
1.7
1
0
0-<0.4
0.4-<1.0

5.0-<9.0
9
cTnl at baseline (ng/ml)
Risk ratio
1.0
1.8
3.5
3.9
6.2
7.8
Accuracy of Cardiac Troponin Assays
According to Time of Onset of Chest Pain
Reichlin T et al. N Engl J Med 2009;361:858-67
High-Sensitivity Troponin Improves
Risk Assessment in ACS Patients
Lindahl B et al. Am Heart J 2010;160:224-9
GUSTO IV Trial
-7,800 patients with NSTE-ACS
enrolled between 1999 to 2000
-random selection of serum
samples in 1,452 patiens
Cardiac biomarkers
-hs-Troponin T (Roche)
-3rd gen Troponin T (Roche)
measured at 48 hours
Troponin Status
-hsTrop neg/Trop T neg: 24%
-hs Trop pos/Trop T neg: 16%
-hs Trop pos/Trop T pos: 60%
Risk Stratification
High-Sensitivity Troponin Assays
Differential
Diagnosis
Non-Cardiac Causes
of Troponin
Elevation Myocardial Injury
Hamm C et al. Eur Heart J 2011
Multidetector CT Parameters Compared
With Coronary Angiography
4-Row
CT
16-Row
CT
64-Row
CT
320-Row
CT
Angiography
250 ms
210 ms
165 ms
175 ms
8 ms
Spatial resolution
1.25 mm
1 mm
0.4 mm
0.4 mm
0.1-0.2 mm
Volume coverage
0.5-3 cm
1-2 cm
2-4 cm
15 cm
-
40 sec
20 sec
10 sec
2 sec
no
Temporal resolution
Breath-hold
CT has Inferior Temporal and Spatial Resolution
Compared With Invasive Angiography
Diagnostic Performance of MultiSlice CT According to Patient Risk
Meijboom WB et al. J Am Coll Card 2007
Pre-test
probability
N
Sensitivity
Specificity
PPV
NPV
High
105
98%
74%
93%
89%
Intermediate
83
100%
84%
80%
100%
Low
66
100%
93%
75%
100%
Low Risk Patient Populations
Litt HI et al. NEJM 2012
Clinical Outcomes @ 30 days
5
ROMICAT-II NEJM 2012
Discharge Diagnosis
100
%
88.6
%
4
80
3
60
2.2
2
40
1.1
1.1
20
1
0
0
Death
2.3
5.2
3.9
MI
Unstable
angina
Coronary
pain
NO ACS
0
MI
Death or
MI
N=1,370
Revasc
N=1,000
Noncoronary
pain
2012 ESC Guidelines for NSTE-ACS
Hamm C et al. Eur Heart J 2011
Recommendation for Risk Stratification
ECG
Biomarkers
Stress test
Coronary CT
High-Risk Indicators
Early Invasive Strategy Warranted
Class IA Indication for Early Invasive Strategy (ESC)
Primary
• Relevant rise or fall in troponin
• Dynamic ST- or T-wave changes
Secondary
•
•
•
•
•
•
•
Diabetes mellitus
Renal insufficiency (eGFR < 60 ml/min)
Reduced LV function (LVEF <40%)
Early post infarction angina
Recent PCI
Prior CABG
Intermediate to high GRACE risk score
GRACE Risk Score
In-hospital Mortality and at 6 Months
Conservative versus Routine Invasive
Strategy in Patients With High Risk NSTE-ACS
Fox K et al. J Am Coll Cardiol 2010
An IPD Meta-Analysis of FRISC-II, ICTUS, and RITA-3 Trials
Cardiac Death or MI @ 5 Years
HR 0.81
(95% CI 0.71 to 0.93)
P=0.002
Cardiac Death
Myocardial Infarction
Invasive Angiography in NSTE-ACS
NSTE-ACS ESC Guidelines - Hamm C et al. Eur Heart J 2011
High-Risk Criteria
Risk
Stratification
Acute
Myocardial
Infarction
Update on
Prehospital
Medications
Patient and
System Delay
Benefits of Primary PCI Over Thrombolysis
•
Higher IRA Patency
•
↓ Risk of Reocclusion
(Reinfarction)
•
↓ Infarct Size
•
↑ ST Resolution
•
↑ TIMI Flow and MBG
Lange RA. NEJM 2002;346:945
Patient S.V, male, 51 YO
Strong, persistend retrosternal chest pain
Lävo
LAD Occlusion
Patient S.V, male, 51 YO
Strong, persistend retrosternal chest pain
Aspiration
Patient S.V, male, 51 YO
Strong, persistend retrosternal chest pain
Stent before
Result
Primary PCI versus Thrombolysis in AMI
Keeley EC et al. Lancet 2003;361:13
16
 43%
 22%
 57%
P<0.001
P=0.002
P<0.001
Meta-Analysis
-N=7739 patients
-23 randomized trials
-8x:streptokinase vs PCI
-15x: tPA vs PCI
14
12
8
8
9
7
7
4
 50%
 95%
P<0.008
P<0.001
3
1
2
0
Death, MI,
Stroke
Death
Reinfarction
PCI
Stroke
0.05
1
ICH
Thrombolysis
23 death prevented and 44 MI’s and 11 strokes avoided for every 1000 pts
treated with primary PCI instead of thrombolysis
Relationship Between Time to Reperfusion,
Myocardial Salvage, and Mortality Reduction
Gersh B et al. JAMA 2005;293:979-86
Windecker S et al. Lancet 2013; 382:644-57
Number of Deaths Associated With
Increases in Door-to-Balloon Time
Nallamothu BK et al. N Engl J Med 2007
Systems of Care for Patients With STEMI
Danchin N. J Am Coll Cardiol Intv 2009; 2:901– 8
30-Days Mortality According to Number of Medical
Parties Involved Before Admission
14
%
12.1
12
10
7.1
8
6
5.5
4
2
0
Median Time
From 1st Call
to Reperfusion
(range)
0 or 1 Party
2 Parties
100 min
(50-170)
122 min
(60-201)
≥3 Parties
155 min
(80-270)
Optimizing Delays in The Management of STEMI
Windecker S et al. Lancet 2013; 382:644-57
Network: Logistics of Pre-Hospital Care
Risk
Stratification
Acute
Myocardial
Infarction
Update on
Prehospital
Medications
Patient and
System Delay
Targets for Antithrombotic Therapy
Curzen N et al. Lancet 2013; 382:633-43
Platelet Inhibition – Competing Risks
ASA
ASA + Clopidogrel
ASA +
Prasugrel/Ticagrelor
Reduction
in
Ischemic
Events
- 22%
- 20%
- 19%
+ 60%
Placebo
APTC
Single
Antiplatelet Rx
+ 38%
+ 32%
CURE
TRITON-TIMI 38
Dual
Antiplatelet Rx
Higher
IPA
Increase
in
Major
Bleeds
Assessment of Bleeding-Risk
Hamm C et al. ESC Guidelines NSTEM-ACS Eur Heart J 2011









Age (>75)
Renal failure
Low body weight (<60kg)
Female gender
Anemia
High dose antithrombotic agents
Duration of antithrombotic Rx
Combination of several
antithrombotic agents
Change between various
antithrombotic agents
ST-Elevation ACS
Non ST-Elevation ACS
Benefit of Aspirin in NSTE-ACS:
Four Randomized Trials
Death and MI (%)
20
P=0.0005
P=0.012
15
12.9
P<0.0001
17.1
11.9
10.1
10
5
P=0.008
5
6.5
6.2
3.3
0
Lewis et al
Cairns et al
NEJM 1983
(N=333)
NEJM 1985
(N=555)
Aspirin
Theroux et al
RISC group
NEJM 1988
(N=239)
Placebo
Note: 150–300 mg oral LD = 80–150 mg i.v. LD
Lancet 1990
(N=796)
CURRENT OASIS 7 – Acute Coronary Syndromes
Aspirin Double Dosage
Mehta SR et al. N Engl J Med 2010;363:930-42
Primary outcome: CV death, MI or stroke at 30 days
High dose
(300-325 mg)
QuickTime™
are
decompressor
needed toand
seeathis picture.
versus
low dose
(75-100 mg)
Aspirin
Major GI Bleeding: 0.4% (high dose) vs 0.2% (low dose), P=0.04
Mode of Action of P2Y12 Inhibitors:
Clopidogrel, Prasugrel, Ticagrelor
Schömig A. N Engl J Med 2009;361:1108-1111
Limitations of Clopidogrel
1. Delayed onset of action
2. Large interindividual
variability in platelet
response
3. Irreversibility of inhibitory
action
Novel Oral P2Y12 Inhibitors in ACS
Primary Endpoint: CV Death, MI or Stroke
TIMI-TRITON 38
PLATO
Wiviott SD et al. N Engl J Med 2007
Wallentin L al. N Engl J Med 2009
11.7%
9.8%
Ticagrelor vs. Clopidogrel for ACS
in Patients Intended to Treat Non-Invasive
James SK et al. BMJ 2011, 342:d3527. doi: 10.1136/bmj.d3527
NON –
CARDIOVASCULAR DEATH, MI
OR STROKE (%)
INVASIVE
|
NON - INVASIVE STRATEGY
HR 0.85, 95%CI 0.73 to 1.00
INVASIVE
ACCOAST design
NSTEMI + Troponin ≥ 1.5 times ULN local lab value
Clopidogrel naive or on long term clopidogrel 75 mg
Randomize 1:1
n~4100 (event driven)
Double-blind
CABG
or
Medical
Management
(no more prasugrel)
Prasugrel 30 mg
Placebo
Coronary
Angiography
Coronary
Angiography
Prasugrel 30 mg
Prasugrel 60 mg
PCI
PCI
CABG
or
Medical
Management
(no prasugrel)
Prasugrel 10 mg or 5 mg (based on weight and age) for 30 days
1° Endpoint: CV Death, MI, Stroke, Urg Revasc, GP IIb/IIIa bailout, at 7 days
Montalescot G et al. Am Heart J 2011;161:650-656
Pretreatment With Prasugrel in NSTE-ACS
ACCOAST Trial - Montalescot G et al. N Eng J Med 2013; 369:999-1010.
Primary Efficacy Endpoint
Key Safety Endpoint
CV Death, MI, Stroke, Urgent
Revasc, or GP IIb/IIIa Bailout
TIMI Major Bleeding
Comparison of Fondaparinux and
Enoxaparin in Patients With NSTE-ACS
Yusuf S et al. NEJM 2006
1°EP: Death, MI, or
Refractory Angina @ 9 days
Safety EP: Major Bleeding
@ 9 days
Checklist of Antithrombotic
Treatments in NSTE-ACS
Antithrombotic
Aspirin
P2Y12 Inhibitor
Anticoagulation
Drug
Class and Level
of Evidence
Aspirin 150-300 mg po
(80-150 mg i.v.) loading,
75-100 mg qd maintenance
IA
Ticagrelor 180 mg po
loading dose,
90 mg BID maintenance
IB
Fondaparinux 2.5 mg sc qd
IA
ST-Elevation ACS
Non ST-Elevation ACS
Randomised Trial of Intravenous Streptokinase, Oral
Aspirin, Both, or Neither among 17187 Cases of
Suspected Acute Myocardial Infarction: ISIS-2
80
0
60
0
Streptokinase:
791 vascular
deaths (9.2%)
40
0
20
0
Placebo tablets:
1016 vascular deaths
(11.8%)
80
0
60
0
Aspirin:
804 vascular deaths
(9.4%)
40
0
20
0
0
0
7
14
21
28
Days of randomisation
35
7
14
21
28
35
Placebo infusion and tablets:
568 vascular
deaths (13.2%)
500
Cumulative number of vascular deaths
1000
Cumulative number of vascular deaths
Cumulative number of vascular deaths
Placebo infusion:
1029 vascular deaths
1000
(12.0%)
40
0
30
0
20
0
10
0
Streptokinase and Aspirin:
343 vascular deaths
(8.0%)
0
Days of randomisation
ISIS-2 Collaborative Group, Lancet 1988; II:349-360
7
14
21
28
Days of randomisation
35
Novel Oral P2Y12 Inhibitors in STEMI
Primary Endpoint: CV Death, MI or Stroke
TIMI-TRITON 38
Montalescot G et al. Lancet 2009;373:732–731
PLATO
Steg PG et al. Circulation 2010;122:2131-41
HR=0.87, 95% CI 0.75-1.01, P=0.07
Novel Oral P2Y12 Inhibitors in STEMI
Primary Safety Endpoint: Major Bleeding
TIMI-TRITON 38
Montalescot G et al. Lancet 2009;373:732–731
PLATO
Steg PG et al. Circulation 2010;122:2131-41
Checklist of Antithrombotic
Treatments in STEMI
Antithrombotic
Aspirin
P2Y12 Inhibitor
Anticoagulation
Drug
Aspirin 150-300 mg po
(80-150 mg i.v.) loading, 75100 mg qd maintenance
Ticagrelor 180 mg po loading,
90 mg BID maintenance dose
OR
Prasugrel 60 mg loading,
10 mg maintenance dose in
clopidogrel-naive pts, age <75
years, without prior stroke
Unfractionated Heparin
OR
Bivalirudin
Class and Level
of Evidence
IA
IB
IB
IC
IB
WARNHINWEISE
KONTRAINDIKATIONEN
Kontraindikationen und Warnhinweise für
Thrombozyten-Aggregationshemmer
Clopidogrel
Prasugrel
- Aktive Blutung
- Aktive Blutung
- Schwere Leberinsuffizienz - Schwere Leberinsuffizienz
- St.n. TIA/CVI
Ticagrelor
-
Aktive Blutung
Schwere Leberinsuffizienz
St.n. intrakranieller Blutung
Co-Administration von
CYP3A4 Inhibitoren
(Ketokonazol, Clarithromcycin)
- Thrombotischthrombozytopenische
Purpura
- CVI <7 Tage
- Omeprazol, Esomeprazol,
Fluoxetin, Ciprofloxacin,
Carbamazepin
- Alter ≥75 Jahre
- Körpergewicht <60 kg
- Thrombotischthrombozytopenische
Purpura
- Galactose-Intoleranz
- Orale Antikoagulation
- Sick-Sinus-Syndrom, AVBlock II und III
- Asthma , COPD
- Hyperurikämie/Gicht
- Rifampicin, Dexamethason,
Phenytoin, Carbamazepin,
Phenobarbital, Digoxin
- Orale Antikoagulation