thrombolysis assisted pci bonnie h. weiner md msec mba fscai past president scai professor of...
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Thrombolysis assisted PCIThrombolysis assisted PCI
Bonnie H. Weiner MD MSEC MBA FSCAIPast President SCAI
Professor of MedicineDirector Interventional Cardiology Research
St Vincent Hospital @ Worcester Medical Center
Bonnie H. Weiner MD MSEC MBA FSCAIPast President SCAI
Professor of MedicineDirector Interventional Cardiology Research
St Vincent Hospital @ Worcester Medical Center
DisclosureDisclosure
I am an Interventional Cardiologist I believe every STEMI patient should have PCI I deal with reality and recognize that this may not be possible everywhere today General Disclosures
Ownership Imaging Core Lab Services Davol AtheroMed
Consulting Boston Biomedical Associates
CR Bard Labcoat Therox
Cormend Research
Medtronic Boston Scientific Abbott
Honoraria SCAI
I am an Interventional Cardiologist I believe every STEMI patient should have PCI I deal with reality and recognize that this may not be possible everywhere today General Disclosures
Ownership Imaging Core Lab Services Davol AtheroMed
Consulting Boston Biomedical Associates
CR Bard Labcoat Therox
Cormend Research
Medtronic Boston Scientific Abbott
Honoraria SCAI
PCI in STEMIPCI in STEMI
Primary PCI PCI immediately following successful
fibrinolysis Rescue PCI in failed fibrinolysis Facilitated PCI
Primary PCI PCI immediately following successful
fibrinolysis Rescue PCI in failed fibrinolysis Facilitated PCI
Repeat ThrombolysisAccelerated tPA or
reteplase
n=142
Primary Endpoint:Composite of death, reinfarction, CVA, or severe heart failure at 6 months
REACT: 6 month resultsREACT: 6 month results
NEJM 2005;353:2758
427 Acute MI patients with failed thrombolysisaspirin thrombolytic therapy (60% received streptokinase) within 6 hours of
chest pain onset, <50% resolution of ST changes on ECG at 90 minutes
42% anterior infarctions
Conservative Treatment
IV Unfractionated Heparinfor 24 hours
n=141
Rescue PCI
Angiography with or without Revascularization
n=144
REACT: 6 Month ResultsREACT: 6 Month ResultsPrimary Composite Endpoint at
6Months(Death, MI, CVA, or severe heart failure) The primary composite
endpoint of death, MI, CVA or severe heart failure at 6 months was significantly lower in the rescue PCI group compared with either the repeat thrombolysis group or the conservative management group
RepeatThrombolysis
Rescue PCI ConservativeManagement
•p<0.001 •p=0.002
Facilitated PCIFacilitated PCI
a strategy of planned immediate PCI after administration of an initial pharmacological regimen intended to improve coronary patency before the procedure. These regimens have included high-dose heparin, platelet glycoprotein (GP) IIb/IIIa inhibitors, full-dose or reduced dose fibrinolytic therapy, and the combination of a GP IIb/IIIa inhibitor with a reduced-dose fibrinolytic agent (e.g., fibrinolytic dose typically reduced 50%).
a strategy of planned immediate PCI after administration of an initial pharmacological regimen intended to improve coronary patency before the procedure. These regimens have included high-dose heparin, platelet glycoprotein (GP) IIb/IIIa inhibitors, full-dose or reduced dose fibrinolytic therapy, and the combination of a GP IIb/IIIa inhibitor with a reduced-dose fibrinolytic agent (e.g., fibrinolytic dose typically reduced 50%).
*ACC/AHA 2007 Focused update STEMI Guidelines
RationalRational
Primary PCI appears superior to thrombolysis but not all patients have the required prompt (DTB < 90 minutes) access to the cath lab.
Treatment delays are common and reduce the true benefit of PCI
TIMI 3 flow prior to PCI is an important predictor of success and clinical outcome
Primary PCI appears superior to thrombolysis but not all patients have the required prompt (DTB < 90 minutes) access to the cath lab.
Treatment delays are common and reduce the true benefit of PCI
TIMI 3 flow prior to PCI is an important predictor of success and clinical outcome
Facilitated PCIFacilitated PCI
A number of small studies suggested a benefit to several approaches
CAPITAL-AMI 170 patients with STEMI randomized to TNK
vs. TNK facilitated PCI Primary endpoint: death, re MI, recurrent
unstable ischemia or stroke at 6 months
A number of small studies suggested a benefit to several approaches
CAPITAL-AMI 170 patients with STEMI randomized to TNK
vs. TNK facilitated PCI Primary endpoint: death, re MI, recurrent
unstable ischemia or stroke at 6 months
CAPITAL-AMICAPITAL-AMI
% W
ith C
ompo
site
End
poin
t
Days form Randomization
JACC 2005;46:417
p=0.04
24.4%
11.6%
•A
•D
•M
•I
•R
•A
•L
bciximab before
irect Angioplasty and Stenting in
yocardial
nfarction
egarding
cute and
ong term follow-up
ADMIRAL StudyADMIRAL Study
NEJM 2001;334:1895
Aim of the StudyAim of the Study•To demonstrate the superiority of abciximab over placebo in primary PTCA with stenting in acute myocardial infarction
•ESC
DesignDesign•AMI < 12 hours
randomized
•Abciximab
+
•Heparin, ASA, Ticlopidine
•Placebo
+
•Heparin, ASA, Ticlopidine
•First Coronary Angiography
PTCA + Stent
•First Coronary Angiography
PTCA + Stent
•Coronary Angiography
at 24 h and 6 Months
•Coronary Angiography
at 24 h and 6 Months
•Clinical evaluation
(24 h, 30 Days and 6 Months
Primary Endpoint (6 months)Primary Endpoint (6 months)
7.4
15.9
•0
•5
•10
•15
•20
% o
f P
atie
nts
p = 0.02
- 52.3 %
Death, Recurrent MI, Urgent TVRDeath, Recurrent MI, Urgent TVR
Placebo
n = 150
Abciximab
n = 150
Primary Endpoint Components (6 Months)Primary Endpoint Components (6 Months)
7.3
3.4
4.0
6.6
2.02.0
0
5
10
Death Recurrent MI Urgent TVR
% o
f P
atie
nts
Placebo Abciximab
p = 0.33
- 54.8%
- 35.0%
p = 0.02
Secondary Endpoint (6 Months)Secondary Endpoint (6 Months)Death, Recurrent MI, Any RevascularizationDeath, Recurrent MI, Any Revascularization
22.8
33.8
•0
20
30
40
% o
f P
atie
nts
p = 0.03
- 39.5 %
Placebo
n = 150
Abciximab
n = 150
Bleeding Events (30 Days)Bleeding Events (30 Days)
3.3
12.1
00.7
0
2
4
6
8
12
Major Minor
% o
f P
atie
nts
Placebo Abciximab
p = 0.50
p = 0.004
Facilitated PCI: Limits of the DataFacilitated PCI: Limits of the Data
Conflicting studies: Currently is Class IIb, abciximab, anterior location, < 75 years old, no risk factors for bleeding, + planned PCI* Most show improved TIMI flow rates or less
reinfarction Other harder endpoints such as death have been
harder to prove Several recently presented larger trials:
ASSENT 4: Negative study, stopped prematurely FINESSE: Reported at the ESC 2007
Conflicting studies: Currently is Class IIb, abciximab, anterior location, < 75 years old, no risk factors for bleeding, + planned PCI* Most show improved TIMI flow rates or less
reinfarction Other harder endpoints such as death have been
harder to prove Several recently presented larger trials:
ASSENT 4: Negative study, stopped prematurely FINESSE: Reported at the ESC 2007
*ACC/AHA 2004 STEMI Guidelines
ASSENT-4: Full Dose Fibrinolytic with PCI vs. PCI Alone
ASSENT-4: Full Dose Fibrinolytic with PCI vs. PCI Alone
Full dose tenecteplase N=4000 Primary endpoint: death or CHF or
cardiogenic shock at 90 days Study stopped at 1667 patients by the
DSMB due to superiority of the PCI only arm
Full dose tenecteplase N=4000 Primary endpoint: death or CHF or
cardiogenic shock at 90 days Study stopped at 1667 patients by the
DSMB due to superiority of the PCI only arm
Lancet 2006;367:569
ASSENT- 4: Outcomes at 90 days (primary end point)
ASSENT- 4: Outcomes at 90 days (primary end point)
End point TNK+PCI (%)
PCI alone (%)
p
Death/CHF/cardiogenic shock
18.8 13.7 0.0055
ASSENT- 4: Outcomes at 90 days
ASSENT- 4: Outcomes at 90 days
Lancet 2006;367:569
End point TNK+PCI (%)
PCI alone (%)
p
Death 6.7 5.0 0.141
Cardiogenic shock
6.1 4.8 0.273
CHF 12.1 9.4 0.078
ASSENT- 4 secondary end points at 90 days
ASSENT- 4 secondary end points at 90 days
Lancet 2006;367:569
End point TNK+PCI (%)
PCI alone (%)
p
Re-MI 6.1 3.5 0.020
Repeat TVR 6.6 3.6 0.006
Stroke 2.65 0.10 <0.0001
Intracranial hemorrhage
1.09 0.10 <0.05
Major bleeds (in hospital)
5.6 4.4 0.3118
•3000 pts STEMI•Chest pain <6 h•ASA (150-325 mg)•Heparin (40 U/kg, 3000) or•Enoxaparin (.5/.3 mg/kg iv/sc)
FACILITATED PCI•Abciximab (.25/.125)•Reteplase (5 IU + 5 IU)
in the ED• (single bolus for age>75)•PCI 60-120 mins
PRIMARY PCI•Angio/PCI •60-120 minutes•Abciximab during
PCI in CCL
1° Endpoint 90 day death, CHF,VF, shock
Double-blind, randomized, triple-dummy placebo-controlled
ABCIXIMAB
FACILITATED PCI•Abciximab in ER•Angio/PCI •60-120 minutes
Ellis S. European Society of Cardiology Congress 2007; September 3, 2007; Vienna, Austria.
•*All-cause mortality; rehospitalization or emergency department treatment for CHF; resuscitated ventricular fibrillation occurring >48 hours after randomization; cardiogenic shock•ED=emergency department
FINESSEFINESSE
End point Primary PCI (%)
Abciximab-facilitated (%)
Combination (abciximab/reteplase)-facilitated (%)
p, combination-facilitated vs primary PCI
p, combination-facilitated vs abciximab-facilitated
Primary end point*
10.7 10.5 9.8 NS NS
All-cause mortality
4.5 5.5 5.2 NS NS
Complications of MI
8.9 7.5 7.4 NS NS
CHF requiring hospital/ED visit
2.2 2.9 1.9 NS NS
Death 4.5 5.5 5.2 NS NS
Ellis S. European Society of Cardiology Congress 2007; September 3, 2007; Vienna, Austria.
Primary, Secondary, and Bleeding End Points in FINESSE
Primary, Secondary, and Bleeding End Points in FINESSE
End point Primary PCI (%)
Abciximab-facilitated (%)
Combination (abciximab/reteplase)-facilitated (%)
p, combination-facilitated vs primary PCI
p, combination-facilitated vs abciximab-facilitated
Cardiogenic shock
6.8 4.8 5.3 NS NS
VF 0.4 0.2 0.6 NS NS
TIMI major bleeding
2.6 4.1 4.8 0.025 NS
TIMI minor bleeding
4.3 6.0 9.7 <0.001 0.006
TIMI major or minor bleeding
6.9 10.1 14.5 <0.001 0.008
*All-cause mortality; rehospitalization or emergency department treatment for CHF; resuscitated ventricular fibrillation occurring >48 hours after randomization; cardiogenic shock•VF=ventricular fibrillation
Ellis S et al. N Engl J Med 2008;358:2205-2217
FINESSEFINESSE
Transfer-MITransfer-MI
Randomized trial of pharmacoinvasivestratagy Routine transfer within 6 hours
vs Rescue PCI for high risk STEMI
Randomized trial of pharmacoinvasivestratagy Routine transfer within 6 hours
vs Rescue PCI for high risk STEMI
ResultsResults
ResultsResults
ResultsResults
Level 1 MI Treatment TimesLevel 1 MI Treatment Times
Minutes (median)
In door 1 outdoor 1
Transport time
In door 2 - balloon
Total In door to balloon
Zone I(n=775)
Zone II(n=557)
AN(n=360)
DANAMI(n=567)
49(36,66)
60(48,83)
NA
50(39-65)
22(16,31)
35(26,49)
NA
32(20-45)
21(16,28)
19(15,25)
65(47,83)
26(20-38)
95(82,116)
122(101,151)
65(47,83)
108
•Adair
•Adams
•Allamakee
•Appanoose
•Audubon
•Benton
•Black Hawk
•Boone
•Bremer
•Buchanan
•Buena Vista •Butler
•Calhoun
•Carroll
•Cass
•Cedar
•Cerro Gordo
•Cherokee
•Chickasaw
•Clarke
•Clay
•Clayton
•Clinton
•Crawford
•Dallas
•Davis•Decatur
•Delaware
•Des Moines
•Dickinson
•Dubuque
•Emmet
•Fayette
•Floyd
•Franklin
•Fremont
•Greene
•Grundy
•Guthrie
•Hamilton
•Hancock
•Hardin
•Harrison
•Henry
•Howard
•Humboldt
•Ida
•Iowa
•Jackson
•Jasper
•Jefferson
•Johnson
•Jones
•Keokuk
•Kossuth
•Lee
•Linn
•Louisa
•Lucas
•Lyon
•Madison •Mahaska•Marion
•Marshall
•Mills
•Mitchell
•Monona
•Monroe•Montgomery
•Muscatine
•O'Brien
•Osceola
•Page
•Palo Alto
•Plymouth •Pocahontas
•Polk
•Pottawattamie
•Poweshiek
•Ringgold
•Sac
•Scott•Shelby
•Sioux
•Story•Tama
•Taylor
•Union
•Van Buren
•Wapello
•Warren •Washington
•Wayne
•Webster
•Winnebago
•Winneshiek
•Woodbury
•Worth
•Wright
•Primary •Secondary •Tertiary
•Level 1 Heart Attack Program
•Report Card – February 1, 2004 to June 30, 2007Report Card – February 1, 2004 to June 30, 2007
Mercy Zone 1 Zone 2
N=848 N=509 N=187 N=152
Median D-B (min) 60 100 134
30 Day Mortality(4.2%) 4.5% 2.1% 5.9%
•Blue = 30 miles- 15 min flight time (each way)
•Red= 60 miles- 23 min flight time (each way)
•GEISINGER: RURAL PENNSYLVANIA
GEISINGER RESULTSGEISINGER RESULTS•Patients Transferred to GMC
2004(n = 110)
2005(n = 134)
2006(n = 143)
2007(n = 63)
D2B
(Minutes)
189 113 105 96
•10 PCI centers•16 Transfer for PCI•28 Lytics•11 Mixed
•RACE Centers and Regions65 hospitals (10 PCI, 55 non PCI)
•Asheville
•Winston-Salem•Durham-Chapel Hill-
•Greensboro
•Charlotte
•East Carolina
•Each non-PCI center was assessed for
•reperfusion designation based on resources, transfer ability, and transfer time to PCI center
•Adair
•Adams
•Allamakee
•Appanoose
•Audubon
•Benton
•Black Hawk
•Boone
•Bremer
•Buchanan
•Buena Vista •Butler
•Calhoun
•Carroll
•Cass
•Cedar
•Cerro Gordo
•Cherokee
•Chickasaw
•Clarke
•Clay
•Clayton
•Clinton
•Crawford
•Dallas
•Davis•Decatur
•Delaware
•Des Moines
•Dickinson
•Dubuque
•Emmet
•Fayette
•Floyd
•Franklin
•Fremont
•Greene
•Grundy
•Guthrie
•Hamilton
•Hancock
•Hardin
•Harrison
•Henry
•Howard
•Humboldt
•Ida
•Iowa
•Jackson
•Jasper
•Jefferson
•Johnson
•Jones
•Keokuk
•Kossuth
•Lee
•Linn
•Louisa
•Lucas
•Lyon
•Madison •Mahaska•Marion
•Marshall
•Mills
•Mitchell
•Monona
•Monroe•Montgomery
•Muscatine
•O'Brien
•Osceola
•Page
•Palo Alto
•Plymouth •Pocahontas
•Polk
•Pottawattamie
•Poweshiek
•Ringgold
•Sac
•Scott•Shelby
•Sioux
•Story•Tama
•Taylor
•Union
•Van Buren
•Wapello
•Warren •Washington
•Wayne
•Webster
•Winnebago
•Winneshiek
•Woodbury
•Worth
•Wright
•Primary •Secondary •Tertiary
•Level 1 Heart Attack Program
•Report Card – February 1, 2004 to June 30, 2007Report Card – February 1, 2004 to June 30, 2007
Mercy Zone 1 Zone 2
N=848 N=509 N=187 N=152
Median D-B (min) 60 100 134
30 Day Mortality(4.2%) 4.5% 2.1% 5.9%
•Blue = 30 miles- 15 min flight time (each way)
•Red= 60 miles- 23 min flight time (each way)
•GEISINGER: RURAL PENNSYLVANIA
GEISINGER RESULTSGEISINGER RESULTS•Patients Transferred to GMC
2004(n = 110)
2005(n = 134)
2006(n = 143)
2007(n = 63)
D2B
(Minutes)
189 113 105 96
•10 PCI centers•16 Transfer for PCI•28 Lytics•11 Mixed
•RACE Centers and Regions65 hospitals (10 PCI, 55 non PCI)
•Asheville
•Winston-Salem•Durham-Chapel Hill-
•Greensboro
•Charlotte
•East Carolina
•Each non-PCI center was assessed for
•reperfusion designation based on resources, transfer ability, and transfer time to PCI center
Focused UpdateFocused Update
Focused UpdateFocused UpdateAlready out of
sync with available
data
ConclusionsConclusions
Large randomized trials of facilitated PCI (fibrinolytics+IIb/IIIa agents) have failed to show a positive benefit and but recent data have at least shown no harm
The latest ACC/AHA (2007) consider facilitated PCI as a class IIb indication but with the more recent data from ASSENT-4 and FINESSE did not change substantially
New Class III recommendation is out of sync with Transfer-MI data and network data (which both AHA and ACCF endorse) and fails to provide an option for patients without access to Primary PCI within 90 minutes
Large randomized trials of facilitated PCI (fibrinolytics+IIb/IIIa agents) have failed to show a positive benefit and but recent data have at least shown no harm
The latest ACC/AHA (2007) consider facilitated PCI as a class IIb indication but with the more recent data from ASSENT-4 and FINESSE did not change substantially
New Class III recommendation is out of sync with Transfer-MI data and network data (which both AHA and ACCF endorse) and fails to provide an option for patients without access to Primary PCI within 90 minutes
Facilitated PCI should not be first line therapy if primary PCI is available within 90 minutes
It is a reasonable alternative however when it is not possible to provide primary PCI because of:
•Distances•Transfer times•Resources•Cost
If done correctly mortality may approach that seen for primary PCI and will provide more patients with reperfusion therapy
•Thank You