Transcript Document

Crotone Cardiologia, 1-2 Ottobre 2010
SCA: RISULTATI E POSSIBILITA’ DELLA
CARDIOLOGIA INTERVENTISTICA
Luigi Inglese, MD and Francesco Casilli, MD
IRCCS Policlinico San Donato, Milano, Italy
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Pathophysiology of ACS
two major causes of coronary thrombosis:
plaque rupture and endothelial erosion
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
2
Pathophysiology of ACS
two major causes of coronary thrombosis:
plaque rupture and endothelial erosion
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
3
ACS with persistent
ST-segment elevation
ACS without persistent
ST-segment elevation
Platelet-fibrin
thrombus
Platelet-rich
thrombus
“White thrombus”
Large fibrin-red blood cell propagation
component, susceptible to fibrinolysis,
mostly occlusive
CK-MB or Troponin
Usually non-occlusive
Troponin elevated or not
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
4
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
5
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
• NSTE-ACS
is
the
most
frequent
manifestation of ACS and represents the
largest group of pts undergoing PCI
• Pts with NSTE-ACS
constitute a very
heterogeneous group with highly variable
prognosis
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
6
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Risk stratification
•
Early risk stratification is important to identify pts at high
immediate and long-term risk of death and cardiovascular
events, in whom an early invasive strategy with its adjunctive
medical therapy may reduce that risk
•
It is equally important
to identify pts at low risk in whom
potentially
and
hazardous
costly
invasive
and
medical
treatments provide little benefit or in fact may cause harm
•
Risk
should
be
evaluated
considering
different
clinical
characteristics, ECG changes, and biochemical markers
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
7
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Risk stratification
•
The ESC Guidelines for
NSTE-ACS recommend the
GRACE risk score as the
preferred classification to
apply on admission and at
discharge in daily clinical
practice
http://www.outcomes-umassmed.org/grace
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
8
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Risk stratification
•
A substantial benefit with an early invasive strategy has only been
proved in pts at High-Risk
•
The recently published meta-analysis (including the FRISC II, the
ICTUS and the RITA III trials) showed a direct relationship
between risk* and benefit from an early invasive approach
* evaluated by a set of risk indicators including age, diabetes,
hypotension, ST depression and body mass index (BMI)
•
Troponin elevation and ST depression at baseline appear to be
among the most powerful individual predictors of benefit from
invasive treatment
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
9
Randomized clinical trials comparing
different invasive treatment strategies
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
10
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Early invasive or conservative strategies
•
Randomized Clinical Trials (RCTs) have shown that an early
invasive strategy reduces ischaemic endpoints mainly by
reducing severe recurrent ischaemia and the clinical need for
rehospitalization and revascularization
•
These trials have also shown a clear reduction in mortality and
myocardial infarction (MI) in the medium term, while the
reduction in mortality in the long term has been moderate and
MI rates during the initial hospital stay have increased (early
hazard)
Mehta SR, Cannon CP, Fox KA et al. Routine vs selective invasive strategies in patients with acute
ACC/AHA
2009 Joint
STEMI/PCI
Guidelines
Focused Update
coronary syndromes: a collaborative meta-analysis of randomized
trials.
JAMA
2005; 293:
2908–2917
11
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Early invasive or conservative strategies
•
The most recent meta-analysis confirms that an early invasive
strategy reduces cardiovascular death and MI at up to 5 years of
follow-up
Fox KA, Clayton TC, Damman P et al. Long-term outcome of a routine versus selective invasive strategy in patients
with non-ST-segment elevation acute coronary syndrome a meta-analysis of individual patient data. J Am Coll Cardiol
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
2010; 55: 2435–2445
12
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Early invasive or conservative strategies
Fox KA, Clayton TC, Damman P et al. Long-term outcome of a routine versus selective invasive strategy in patients
with non-ST-segment elevation acute coronary syndrome a meta-analysis of individual patient data. J Am Coll Cardiol
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
2010; 55: 2435–2445
13
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Timing of angiography and intervention
•
There is no evidence that any particular time of delay to
intervention
with
upstream
pharmacological
treatment,
including intensive antithrombotic agents, would be superior to
providing
adequate
medical
treatment
and
performing
angiography as early as possible
•
Ischaemic events as well as bleeding complications tend to be
lower and hospital stay can be shortened with an early as
opposed to a later invasive strategy
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
14
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Timing of angiography and intervention
•
In High-Risk pts (GRACE risk score > 140) urgent angiography
should be performed within 24 h if possible
•
Pts with a high thrombotic risk or high risk of progression to MI
should be investigated with angiography without delay
•
In lower risk subsets of NSTE-ACS pts, angiography and
subsequent revascularization can be delayed without increased
risk but should be performed during the same hospital stay,
preferably within 72 h of admission
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
15
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Indicators predicting high thrombotic risk or high-risk for progression to
myocardial infarction, which indicate emergent coronary angiography
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
16
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
17
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Coronary angiography, PCI and CABG
•
An invasive
always starts with angiography. After defining the
anatomy and its associated risk features, a decision about the type
of intervention can be made. The mode of revascularization should
be based on the severity and distribution of the CAD
•
The angiography in combination with ECG changes often identifies
the culprit lesion with irregular borders, eccentricity, ulcerations,
and filling defect suggestive of intraluminal thrombi
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
18
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Coronary angiography, PCI and CABG
LM: favourable anatomy to PCI
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
19
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Coronary angiography, PCI and CABG
Distal location
Calcified
Multivessel disease
LM: unfavourable anatomy
to PCI
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
20
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Coronary angiography, PCI and CABG
•
For lesions with borderline clinical significance and in pts with
multivessel
disease,
FFR
measurement
provides
important
information for treatment decision making
•
All trials that have evaluated early vs. late or invasive vs. medical
management have included PCI and CABG at the discretion of the
investigator
•
While the benefit from PCI in pts with NSTE-ACS is related to its
early performance, the benefit from CABG is greatest when pts can
undergo surgery after several days of medical stabilization
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
21
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Coronary angiography, PCI and CABG
N.I. 81 yo
Rx. 35828
05\09\2001
stenting
of2009prox
andGuidelines
ostial
RCA
ACC/AHA
Joint STEMI/PCI
Focused
Update
22
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
23
non-ST-segment elevation acute
coronary syndromes (NSTE-ACS)
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
24
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
25
Primary angioplasty
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Time dependence of benefit of
reperfusion therapy
Hypothetical construct of the relationship between the duration of symptoms of acute
MI before reperfusion therapy, mortality reduction and extent of myocardial salvage
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Delay to reperfusion in patients with acute
myocardial infarction presenting to acute care
hospitals: an international perspective.
Spencer FA et al, Eur Heart J 2010 Mar 15 (Epub ahead of print)
• Data from 5170 STEMI pts enrolled in the GRACE
Registry from 2003 to 2007.
• Median time from hosp presentation to fibrinolysis: 30`.
• Median time from hosp presentation to primary PCI: 86`.
No significant changes in delay times from
2003 to 2007!!
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Applying Classification of Recommendations
and Level of Evidence
Class I
Class IIa
Class IIb
Class III
Benefit >>> Risk
Benefit >> Risk
Additional studies with
focused objectives
needed
Benefit ≥ Risk
Additional studies with
broad objectives needed;
Additional registry data
would be helpful
Risk ≥ Benefit
No additional studies
needed
Procedure/ Treatment
SHOULD be
performed/
administered
IT IS REASONABLE to
perform
procedure/administer
treatment
Procedure/Treatment
MAY BE CONSIDERED
Procedure/Treatment
should NOT be
performed/administered
SINCE IT IS NOT
HELPFUL AND MAY
BE HARMFUL
Level A:
Multiple populations evaluated; Data derived from multiple randomized clinical trials or meta-analyses
Level B:
Limited populations evaluated. Data derived from a single randomized trial or non-randomized studies
Level C:
Very limited populations evaluated. Only consensus opinion of experts, case studies, or standard-of-care.
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Primary angioplasty vs fibrinolysis
• General consensus that primary percutaneous coronary
intervention is the preferred approach to reperfusion
when delivered in expert centres in a timely fashion
Keeley, Boura & Grines. Primary angioplasty versus intravenous thrombolytic therapy
for acute myocardial infarction: a quantitative review
of 2009
23 Joint
randomised
trials.
Lancet
ACC/AHA
STEMI/PCI Guidelines
Focused
Update
2003; 361:12
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Andersen HR et al, NEJM 2003;349:733
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Andersen HR et al, NEJM 2003;349:733
Nielsen PH, Circ 2010; 121: 1484
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
CARESS-IN-AMI
• Designed to address optimum treatment in pts for whom primary PCI not readily
available
• Not a trial of facilitated angioplasty opposed to primary angioplasty
600 STEMI
ASA 300-500 mg IV
Reteplase 5 U+5 U at 30 min
UFH 40 u/kg (max 3000 per u) →7 u/kg/h
Abciximab 0.25 mg/kg bolus →0.125 μg/kg/min for 12 h to a maximum 10 μg/min
RANDOMIZATION
299 assigned to immediate PCI
(mean transp time 110 min)
255 received PCI
Di Mario et al. Lancet 2008;371.
301 assigned to standard
care/rescue PCI
91 received PCI (after 180 min)
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
34
CARESS-IN-AMI: Primary Outcome
primary outcome (composite of all cause mortality, reinfarction, & refractory MI within 30 days)
occurred significantly less often in the immediate PCI group vs. standard care/rescue PCI group
10.7%
4.4%
HR=0.40 (0.21-0.76)
Di Mario et al. Lancet 2008;371.
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
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TRANSFER-AMI
1059 pts with STEMI presenting to non-PCI-capable
hospitals within 12 hrs of symptom onset & with ≥ 1 highrisk feature. All treated with fibrinolytic therapy.
RANDOMIZATION
immediate transfer for PCI
within 6 hours of fibrinolytic
therapy
Cantor et al. N Eng J Med 2009;360:26.
standard treatment after
fibrinolytic therapy (included
rescue PCI)
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
36
High Risk Patients Definition
TRANSFER-AMI
>2 mm ST-segment elevation in 2 anterior
leads or ST elevation at least 1 mm in inferior
leads with at least one of the following:




systolic blood pressure <100 mm Hg
heart rate >100 beats per minute
Killip Class II-III
>2 mm of ST-segment depression in the anterior
leads
 >1mm of ST elevation in right-sided lead V4
indicative of right ventricular involvement
ACC/AHA
Joint
STEMI/PCI
Guidelines Focused Update
Cantor
et2009
al. N
Eng
J Med 2009;360:26.
37
TRANSFER-AMI
primary end point: composite of death, reinfarction, recurrent ischemia, new
or worsening CHF, or shock within 30 days
17.2%
Cumulative Incidence
11.0%
p=0.004
Days
RR= 0.64, 95 CI% (0.47-0.87)
Cantor et al. N Engl J Med 2009;360:26
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
38
TRANSFER-AMI
Study Conclusion
Following treatment with fibrinolytic therapy in
high risk STEMI pts presenting to hospitals
without PCI-capability, transfer to a PCI center
to undergo coronary angiography and PCI
should be initiated immediately without waiting
to determine whether reperfusion has occurred
Cantor et al. N Eng J M 2009;360:26.
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
39
STEMI: ACC/AHA 2009
recommendations for triage
and transfer for PCI
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
40
STEMI: Triage and Transfer for PCI
• Those ptz presenting to a non-PCI-capable
facility should be triaged to fibrinolytic
therapy or immediate transfer for PCI.
• Decision depends on multiple risk clinical
presentation:
– type of STEMI (risk mortality)
– hemorrhagic risk
– time from onset of symptoms
– time required for transport to a PCI-Hub center
(< 90 min)
2009 STEMI Focused Update. Appendix 5
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
41
STEMI: Triage and Transfer for PCI
• Which are pts best suited for transfer to
PCI:
– Those presenting with high-risk features
– Those with high bleeding risk from fibrinolytic
therapy (elderly pts)
– Late presenters >4 h after onset of symptoms
• Decision to transfer is made considering the
time required for transport and the
compliance of the Hub-Centers.
2009 STEMI Focused Update. Appendix 5
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
42
STEMI: Triage and Transfer for PCI
• STEMI pts best suited for fibrinolytic
therapy are those presenting:
– early (< 4h) after symptom onset,
– with a low bleeding risk,
– and/or a low-risk MI.
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
43
STEMI: Triage and Transfer for PCI
• The duration of symptoms should be a
leading factor in selecting a reperfusion
strategy for STEMI patients.
• While patients at high risk (e.g., CHF, shock,
contraindications to fibrinolytic therapy) are
best served with timely PCI, inappropriate
delay between the time from symptom onset
and effective reperfusion with PCI may prove
deleterious, especially among the majority of
STEMI patients at relatively low risk.
2009 STEMI Focused Update. Appendix 5
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
44
STEMI: recommendations for Triage
and Transfer for PCI
II
IIa
IIa
IIb
IIb
III
III
STEMI pts presenting at
Hub-Centers or treatable
invasively in time (< 90`)
should undergo primary PCI
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
45
STEMI: recommendations for Triage
and Transfer for PCI
II
IIa
IIa
IIb
IIb
III
III
It is reasonable to transfer high
risk
patients
who
receive
fibrinolysis as primary reperfusion
therapy to a PCI-capable facility
as soon as possible
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
46
STEMI: recommendations for Triage
and Transfer for PCI
II
IIa
IIa
IIb
IIb
III
III
Patients who are not high risk
who receive fibrinolytic therapy
as primary reperfusion therapy
may be considered for transfer
to a PCI-capable facility as soon
as possible
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
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ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
48
TAPAS
Thrombus Aspiration during Percutaneous
coronary intervention in Acute myocardial infarction
Study
1071 STEMI patients randomized
535 were assigned to
thrombus aspiration
536 were assigned to
conventional PCI
530 complete follow-up at 1 year
530 complete follow-up at 1 year
Svilaas T et al. NEJM 2008;358:557
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Primary endpoint: Myocardial blush grade
60
P < 0.001
Patients (%)
50
40
46
0/1
2
3
41
37
30
20
32
26
17
10
0
Thrombus aspiration
Svilaas T et al. NEJM 2008;358:557
Conventional PCI
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
TAPAS one year outcome: Myocardial blush grade and
death or death/reinfarction at 1 year
P = 0.001
16
14
12
14,8
Death
11
Death/reinfarction
10
7,6
8
6,1
6
4
4,7
3,7
2
0
3
2
0 or 1
Myocardial blush grade
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
FZ 2008-12
Thrombus Aspiration During PCI for
STEMI
II
IIa
IIa
IIb
IIb
III
III
Aspiration thrombectomy is
reasonable
for
pts
undergoing primary PCI
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
52
Use of stents in STEMI
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
53
DES in AMI: TYPHOON
Study Design
Patients Presenting within 12 h after Onset of Symptoms
of a First AMI Requiring Primary PCI of a Native Coronary Artery
Randomisation 1:1
CYPHER® or CYPHER Select®
Sirolimus-eluting Stent
(355 patients)
Any Bare-Metal Stent
(357 patients)
Primary Endpoint: Target Vessel Failure (TVF) at 1 Year
Defined as composite of ischaemia-driven Target Vessel Revascularization (TVR),
recurrent Myocardial Infarction (MI), or Target Vessel-related Cardiac Death
Angiographic Substudy (200 pts): In-stent Late Loss at 8-Months
Dual APT recommended for  6 months
Spaulding C et al. N Engl J Med. 2006;355:1093-104.
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
DES in AMI: TYPHOON
Lower TVF Risk vs BMS
25
Patients (%)
20
1º Endpoint: TVF at 1 year*
15
14.3
49%
10
p=0.0036*
6.2
5
0
BMS
3.1
7.3
300
360
4.2
2.8
0
CYPHER®
60
120
180
Time (days)
240
* TVF defined as ischaemia driven TVR, recurrent MI, or target vessel-related cardiac death
Spaulding C et al. N Engl J Med 2006;355:1093-104.
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
DES in AMI: TYPHOON
Superior Clinical Outcomes vs BMS
30
CYPHER®
p=0.004
BMS
p=NS
p=NS
p<0.001
Patients (%)
25
20
14.3
15
10
7.3
5
0
13.4
TVF*
Primary
Endpoint
5.6
2.3 2.2
1.1 1.4
Death
MI
TVR
* TVF defined as ischaemia-driven TVR, recurrent MI, or target vessel-related cardiac death
Spaulding C, et al. N Engl J Med. 2006;355:1093-104.
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Use of stents in STEMI
I IIa IIb III
It is reasonable to use a DES as an
alternative to a BMS for primary
PCI in STEMI
* Consideration for the use of stents (DES or BMS) in
STEMI should include the possibility of the patient to
comply with prolonged dual antiplatelet therapy, the
bleeding risk in patients on chronic oral anticoagulation,
and the possibility that the patient may need surgery during
the ensuing year
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
57
Use of stents in STEMI
Relative clinical contraindications to the use of DES
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
58
DRUG therapy in STEMI
Glycoprotein IIb/IIIa Receptor
Antagonists
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
59
OnTIME 2: Tirofiban upstream
Acute myocardial infarction
diagnosed in ambulance or referral center
ASA+600 mg Clopidogrel +UFH
Event-free Survival at 30 days
Placebo
Clinical outcome
Tirofiban *
Placebo Tirofiban P-value
Transportation
Death/recurrent MI 39/477
or urgent TVR
(8.2%)
Angiogram
Tirofiban
provisional
van’t Hof et al. Lancet 2008;372:537-46.
33/473
(7.0%)
PCI centre
PCI
0.485
Angiogram
Tirofiban
cont’d
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
60
BRAVE 3: Abciximab upstream
30-days cumul rate of death, recurr MI, IRA revasc, stroke
TREATMENT
pre-PCI treatment with clopidogrel
(600 mg)
followed by abciximab
P= 0.40
vs. placebo
INCLUSION
suspected acute MI (ST change or
LBBB) within 24h of symptom onset
1° OUTCOMES
infarct size, death, stroke, urgent
revascularization of affected artery
No significant difference in infarct size or major bleeding
Mehilli et al. Circ. 2009;119:1933-1940
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
61
Use of Glycoprotein IIb/IIIa Receptor
Antagonists in STEMI
It is reasonable to start treatment with glycoprotein IIb/IIIa
receptor antagonists at the time of primary PCI (with or without
stenting) in selected patients with STEMI (high risk)
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
62
DRUG therapy in STEMI
Thienopyridines
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
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Thienopyridines in STEMI
A loading dose of thienopyridine is recommended
for STEMI patients for whom PCI is planned
II
IIa
IIa
IIb
IIb
III
III
Clopidogrel at least 300 mg to
600 mg should be given as
early as possible before or at
the time of primary PCI
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
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Thienopyridines in STEMI
• The optimal loading dose of clopidogrel
has not been established
• Clopidogrel is a prodrug which must
undergo hepatic conversion to its active
metabolite for platelet inhibition, a process
taking several hours (4-6 h)
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
65
New thienopyridines in STEMI
PRASUGREL (EFIENT)
•
New antiplatelet agent (after 60 mg loading dose 90% pts
have 50% plt inhibition by 1 h)
•
Maintainance dose: 10 mg daily
•
Elimination half-life: 7 h (range 2-15 h)
II
IIa
IIa
IIb
IIb
III
III
Prasugrel loading dose of 60
mg should be given as soon
as possible for primary PCI
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
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TRITON-TIMI 38: Study Design
ACS (STEMI or UA/NSTEMI) & Planned PCI
ASA+UFH
N= 13,600
Double-blind
CLOPIDOGREL
300 mg LD/ 75 mg MD
PRASUGREL
60 mg LD/ 10 mg MD
Median duration of therapy - 12 months
Wiviott SD et al AHJ 152: 627,2006
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
67
TRITON-TIMI 38: Results
15
138
events
Clopidogrel
Endpoint (%)
12.1
CV Death / MI / Stroke
P=0.0004
10
9.9
HR 0.81
(0.73-0.90)
NNT = 46
Prasugrel
35
events
5
TIMI Major
NonCABG Bleeds
P=0.03
HR 1.32
Prasugrel
(1.03-1.68)
2.4 P=0.03
1.8
Clopidogrel
NNH = 167
0
0 30 60 90
180
270
360
450
Days
Wiviott SD et al NEJM 2007;357:2001
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
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TRITON TIMI-38
3
Stent Thrombosis
(ARC Definite + Probable)
Any Stent at Index PCI
N= 12,844
Endpoint (%)
Clopidogrel
2.4
(142)
2
HR 0.48
P <0.0001
1.1
(68)
1
Prasugrel
Significant reductions both with BMS, DES
Significant reductions in early and late stent thromboses NNT= 77
0
0 30 60 90
Wiviott SD et al Lancet 2008
180
Days
270
360
450
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TRITON TIMI-38: Bleeding Events
4
ICH in Pts w
Prior Stroke/TIA
(N=518)
Clopidogrel
Prasugrel
Clop 0 (0) %
Pras 6 (2.3)%
(P=0.02)
% Events
2,4
2
1,8
1,4
0,9
0,9
1,1
0,4
0,1
0,3
0,3
0
TIMI Major
Bleeds
HR 1.32
P=0.03
NNH=167
Life
Threatening
HR 1.52
P=0.01
Nonfatal
P=0.23
Fatal
P=0.002
ICH
P=0.74
Wiviott SD et al NEJM 2007;357: 2001.
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New thienopyridines in STEMI
PRASUGREL (EFIENT)
II
IIa
IIa
IIb
IIb
III
III
In STEMI pts with a prior
history of stroke and TIA for
whom primary PCI is planned,
prasugrel is not recommended as
part of a dual antiplatelet therapy
regimen
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DRUG therapy in STEMI
Anticoagulation
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HORIZONS-AMI: Design
3602 patients with STEMI &
symptom onset ≤ 12 hours
randomized
1800 received bivalirudin alone*
1802 received heparin +
GP IIb/IIIa inhibitor
Emergency angiography
Emergency angiography
Principal management strategy
Principal Management Strategy
Primary PCI, 1678 (93.2%)
Primary PCI, 1662 (92.2%)
Endpoints: Composite of net adverse clinical events (NACE)
Included major bleeding plus MACE (a composite of CVD death, reinfarction, target-vessel
revascularization for ischemia, and stroke within 30 days)
Stone et al. N Eng J Med. 2008;358:2218-30.
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HORIZONS-AMI: Net Adverse Clinical Events
at 30 days
Treatment with bivalirudin alone compared with UFH + GP IIb/IIIa
Inhibitors resulted in reduced 30-day rates of net adverse clinical events
[HR=0.75, (0.62-0.92); p=0.006]
Stone et al. N Eng J Med. 2008;358:2218-30.
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HORIZONS-AMI: Major Bleeding at 30 days
HR=0.59 (0.45-0.76); p<0.0001
* 40% less bleeding in Bivalirudin group at 30 days
Stone et al. N Eng J Med. 2008;358:2218-30.
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Use of Parenteral Anticoagulants
in STEMI
For pts proceeding to primary PCI, who have been treated
with ASA and a thienopyridine, recommended supportive
anticoagulant regimens include:
II
IIa
IIa
IIb
IIb III
III
For prior treatment with UFH, additional
boluses of UFH should be administered as
needed to maintain therapeutic ACT levels
II
IIa
IIa
IIb
IIb
III
III
Bivalirudin is useful as support for primary
PCI with or without prior treatment with
heparin
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Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
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Joint STEMI/PCI
Guidelines Focused Update
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STEMI treatment: Conclusions
• Preferred treatment strategy of STEMI pts is immediate
transportation to a PCI-capable Centre offering
uninterrupted service by a Team of high-volume
operators
• No fibrinolytics should be administered if expected time
delay between first medical contact and balloon inflation
is < 2 h
• If the expected delay is >2 h or > 1.5 h in pts <75 yrs with
large anterior MI and recent outset of symptoms admitted
to a non-PCI Centre, should immediately receive
fibrinolysis and then transferred to a PCI-capable Centre
where angiography and PCI should be performed in a
time window of 3-24h
Guidelines on myocardial revascularization - ESC/EACTS GUIDELINES
- European
Heart Journal
ACC/AHA 2009
Joint STEMI/PCI
Guidelines Focused Update
78
Grazie per
l´attenzione
FORZA VALENTINO!!!
Shanghai,
domenica 25 aprile 2010
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Spoke Centers
Hub Centers
Transfer time ≤ 3h
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
DANAMI-2
Andersen HR et al, NEJM 2003;349:733
Spoke Centers
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Andersen HR et al, NEJM 2003;349:733
Hub Centers
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Andersen HR et al, NEJM 2003;349:733
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Andersen HR et al, NEJM 2003;349:733
CARESS-IN-AMI
• Designed to address optimum treatment in
pts for whom primary PCI not readily
available
• Not a trial of facilitated angioplasty opposed
to primary angioplasty
Di Mario et al. Lancet 2008;371.
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FINESSE: Study design
Treatment
Pre-PCI treatment with ½ -dose lytic plus
abciximab, pre-PCI abciximab alone, and
abciximab at time of PCI
Inclusion
Suspected acute MI (ST change or LBBB)
within 6 h of symptom onset
Exclusion
Low risk (<60 yo, localized inferior infarct)
high risk for bleeding
1° OUTCOMES
Death, VF after 48 hours, shock,
CHF within 90 days
Ellis et al. N Eng J Med. 2008;358:2205-2217.
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Primary, secondary, and bleeding end
points in FINESSE
End point
Primary AbciximabPCI (%) facilitated
(%)
Primary end point* 10.7
at 90 days
>70% ST segment 31.0
Combination
(abciximab/
reteplase)facilitated (%)
p, combinationfacilitated vs
primary PCI
p,
combinationfacilitated vs
abciximabfacilitated
10.5
9.8
NS
NS
33.1
43.9
0.003
0.01
10.1
14.5
<0.001
0.008
resolution within
60–90 min
TIMI major or
minor bleeding
through discharge
or day 7
6.9
*All-cause mortality; rehospitalization or emergency department treatment for CHF; resuscitated
ventricular fibrillation occurring >48 hours after randomization; cardiogenic shock
Ellis et al. N Eng J Med. 2008;358:2205-2217
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Recommendations for the use of
Thienopyridines
For STEMI patients undergoing non-primary PCI, the
following regimens are recommended:
I IIa IIb III
I IIa IIb III
If the patient has received fibrinolytic therapy…
a. …and has been given clopidogrel, it should be
continued as the thienopyridine of choice.
b. …without a thienopyridine, a loading dose of 300-600‡
mg of clopidogrel should be given as the
thienopyridine of choice.
If the patient did not receive fibrinolytic therapy…
c. …either a loading dose of 300-600 mg of clopidogrel
should be given or, once the coronary anatomy is
known and PCI is planned, a loading dose of 60 mg of
prasugrel should be given promptly and no later than 1
hour after the PCI.
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TRANSFER-AMI--Safety Results
• No differences in severe bleeding between 2
groups.
• There was higher incidence of GUSTO mild
bleeding in the pharmaco-invasive group
(13.0% compared to 9.0% in the standard
treatment group, p=0.036).
Cantor et al. N Eng J M 2009;360:26.
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Triage and Transfer for PCI in STEMI
STEMI patient who is a
candidate for reperfusion
Initially seen at a
non-PCI
capable facility
Initially seen at a PCI
capable facility
Send to Cath Lab for
primary PCI
(Class I, LOE:A)
Transfer for primary
PCI
(Class I, LOE:A)
Prep antithrombotic (anticoagulant
plus antiplatelet) regimen
Diagnostic angio
Medical
therapy only
PCI
2009 STEMI Focused Update. Appendix 5
CABG
Initial Treatment
with fibrinolytic
therapy
(Class 1, LOE:A)
At PCI
facility,
evaluate
for timing
of
diagnostic
angio
HIGH RISK
Transfer to a PCI
facility is
reasonable for
early diagnostic
angio & possible
PCI or CABG
(Class IIa,
LOE:B),
High-risk
patients as
defined by 2007
STEMI Focused
Update should
undergo cath
(Class 1: LOE B)
NOT HIGH RISK
Transfer to a PCI
facility may be
considered
(Class IIb,
LOE:C),
especially if
ischemic
symptoms
persist and
failure to
reperfuse is
suspected
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On-TIME 2: Results
Residual ST Deviation after PCI
p=0.003
van’t Hof et al. Lancet 2008;372:537-46
3.6± 4.6mm
4.8± 6.3mm
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Thienopyridines
The duration of thienopyridine therapy
should be as follows:
I IIa IIb III
I IIa IIb III
a. In patients receiving a stent (BMS or DES)
during PCI for ACS, clopidogrel 75 mg daily
or prasugrel 10 mg daily should be given
for at least 12 months;
b. If the risk of morbidity from bleeding
outweighs the anticipated benefit afforded
by thienopyridine therapy, earlier
discontinuation should be considered.
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Thienopyridines
I IIa IIb III
Continuation of clopidogrel or
prasugrel beyond 15 months may
be considered in patients
undergoing DES placement
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Use of Glycoprotein IIb/IIIa Receptor
Antagonists in STEMI
I IIa IIb III
The usefulness of glycoprotein IIb/IIIa receptor
antagonists (as part of a preparatory
pharmacologic strategy for patients with STEMI
prior to arrival in the cardiac catheterization
laboratory for angiography and PCI-UPSTREAM) is
uncertain.
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HORIZONS-AMI: Results
There was a statistically significant 1%
increase in stent thrombosis (n=17) within
the first 24 hours with bivalirudin, but no
subsequent difference (1.3% versus 0.3%,
p<0.001)
Stone et al. N Eng J Med. 2008;358:2218-30.
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LM: favourable anatomy to PCI
Park et al, JACC 2005;45:351
Serruys et al, N Engl J Med 2009;360:961
Chieffo et al, Circulation 2007;116:158
Tamburino et al, Am J Cardiol 2009;103:187
Valgimigli et al, Eurointerv 2007;2:435
Palmerini et al, Eur H J 2009;30:1171
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
LM: favourable anatomy to PCI
Park et al, JACC 2005;45:351
Serruys et al, N Engl J Med 2009;360:961
Chieffo et al, Circulation 2007;116:158
Tamburino et al, Am J Cardiol 2009;103:187
Valgimigli et al, Eurointerv 2007;2:435
Palmerini et al, Eur H J 2009;30:1171
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
LM: unfavourable anatomy to PCI
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Revascularization in non-ST-segment elevation
acute coronary syndromes (NSTE-ACS)
Early invasive or conservative strategies
•
Randomized Clinical Trials (RCTs) have shown that an early invasive strategy
reduces ischaemic endpoints mainly by reducing severe recurrent ischaemia and the
clinical need for rehospitalization and revascularization
•
These trials have also shown a clear reduction in mortality and myocardial infarction
(MI) in the medium term, while the reduction in mortality in the long term has been
moderate and MI rates during the initial hospital stay have increased (early hazard)
•
Mehta SR, Cannon CP, Fox KA et al. Routine vs selective invasive strategies in patients with acute
coronary syndromes: a collaborative meta-analysis of randomized trials. JAMA 2005; 293: 2908–2917
The most recent meta-analysis confirms that an early invasive strategy reduces
cardiovascular death and MI at up to 5 years of follow-up
Fox KA, Clayton TC, Damman P et al. Long-term outcome of a routine versus selective invasive
ACC/AHA
2009
Joint STEMI/PCI
Focused
strategy in patients with non-ST-segment elevation
acute
coronary
syndromeGuidelines
a meta-analysis
ofUpdate
individual patient data. J Am Coll Cardiol 2010; 55: 2435–2445
Revascularization in non-ST-segment elevation
acute coronary syndromes (NSTE-ACS)
•
NSTE-ACS is the most frequent manifestation of ACS and represents the largest group
of pts undergoing PCI
•
Pts with NSTE-ACS constitute a very heterogeneous group of pts with a highly variable
prognosis
•
Early risk stratification is essential for selection of medical as well as interventional
treatment strategies
•
The ultimate goals of coronary angiography and revascularization are mainly two-fold:
symptom relief, and improvement of prognosis in the short and long term
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Revascularization in non-ST-segment elevation
acute coronary syndromes (NSTE-ACS)
Risk stratification
•
Early risk stratification is important to identify pts at high immediate and long-term
risk of death and cardiovascular events, in whom an early invasive strategy with its
adjunctive medical therapy may reduce that risk
•
It is equally important to identify pts at low risk in whom potentially hazardous and
costly invasive and medical treatments provide little benefit or in fact may cause
harm
•
Risk should be evaluated considering different clinical characteristics, ECG changes,
and biochemical markers
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update
Early risk stratification is very
important for selection medical as
well as interventional treatment
strategies.
The ESC guidelines recommend the
GRACE risk score as the preferred
classification to apply in daily clinical
Practice.
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A substantial benefit with an early
invasive strategy has only been proved in
ptz at high risk (age, diabetes,
hypotension, ST depression and BMI).
Troponin elevation and ST depression at
baseline appear to be among the most
powerful individual predictors of benefit
from PCI.
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Timing of invasive investigation
(angiography) has been tested
versus
adeguate
medical
treatment. It should be performed
as early as possible. In high risk
ptz. With a GRACE score > 140,
angiography should be performed
within 24h if possible.
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In lower risk ptz with NSTEACS,
angiography
and
subsequent revasc. Can be
delayed without increased risk
but should be performed
during the same hospital stay
preferably within 72h from
admission
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An invasive strategy always starts with
angiography. After defining the anatomy
and its associated risk features, a
decision about the type of intervention
can be made. The mode of
revascularization should be based on
the severity and distribution of the CAD.
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Angiography in combination with ECG
changes often identifies the culprit lesion.
It is mandatory to intervene on this lesion
first. In case of MVD associated with
culprit there is no RCT evidence that
contemporary treatment is better
vs.treatment of only culprit PCI.
If CABG is considered, benefit is greatest
when pts undergo surgery after several
days of medical stabilization.
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