Download BIAMI - Clinical Trial Results

Heart Care Centers of Illinois
Design
– Single arm, open label, 13 U.S. centers
– Patients with ST-segment elevation
myocardial infarction (STEMI)
• Less than 12 hours duration
• No prior thrombolytic therapy
• Primary PCI required
– Patient population matched to CADILLAC by
inclusion and exclusion criteria
– Comparable efficacy endpoints
Design (cont.)
– Treatment:
Bivalirudin 0.75mg/kg bolus, 1.75mg/kg/hr
infusion for duration of procedure
– Optional post-procedure infusion:
0.25mg/kg/hr
– Abciximab if TIMI flow <3 at end of
procedure
– Primary endpoints of safety and efficacy
evaluated at 7 days/hospital discharge,
30 days and 6 months
Inclusion Criteria
– Symptoms of STEMI for at least 30 min within
previous 12 hours AND
• ST-segment elevation in at least 2 contiguous
leads or new LBBB or existing LBBB with positive
troponin
• Residual high grade stenosis and associated
abnormalities in regional wall motion.
– Planned primary PCI in native coronary
vessel
Exclusion Criteria
– Prior LMWH, Thrombolytics, GP IIb/IIIa inhibitors
– Cardiogenic shock (SBP <80 for >30 min or a need
for intravenous pressors)
– Stroke or neurosurgery within 3 months
– Severe hypertension not adequately controlled by
antihypertensive therapy at the time of study entry
(BP >180/110 mm Hg)
– Life expectancy <1 year
– Heparin only therapy allowed prior to PCI
• 30 minute washout, or
• ACT <250
Primary Endpoints
– Efficacy
Evaluated at 7 days/hospital discharge, at 30 days,
and 6 months composite and individual
components of:
• Death (cardiac and unknown cause)
• Reinfarction
• Repeat intervention/revascularization of target lesion
as a result of ischemia
• Disabling stroke
• Rate of subacute thrombosis at 7 days/hospital
discharge and at 30 days
Primary Endpoints
– Safety
Evaluated at 7 days/hospital discharge:
• Clinically significant bleeding defined as:
– Intracranial, retroperitoneal, or ocular bleeding
– Access site hemorrhage requiring surgical intervention or
a >5cm diameter hematoma
– Reduction in Hgb concentration of >3g/dL with overt
bleeding
– Any blood transfusion
– Any reoperation for bleeding
• Thrombocytopenia
(<100,000 cells/L with a fall of >50% from baseline)
BIAMI Sites
Joseph Stella
Heart Care Centers of Illinois / Heart Care Research Foundation
at St. Francis Hospital and MacNeal Hospital
Jay Ganji
Moses Cone Memorial Hospital
LeBauer Cardiovascular Research Foundation
Garry MacKenzie
McKay-Dee Hospital Center
John McKnight
Monongalia General Hospital
Kevin Browne
Lakeland Regional Medical Center
Watson Clinic Center for Research
Anil Sahijwani &
Monica ValGarijo
University Community Hospital
Pepin Heart & Vascular Institute
Abnash Jain
West Virginia University Hospital
Ron Waksman
Cardiovascular Research Institute
Washington Hospital Center
Michael Attubato
New York University Medical Center
Ali Rizvi &
Matthew French
The Care Group at The Heart Center of Indiana and
St Vincent Hospital of Indianapolis
J. Kern Buckner
South Denver Cardiology Associates
Robert Applegate
Wake Forest Baptist Medical Center
Enrollment and Follow-up
Patients Enrolled
201
ITT 201
Cath Only 4
PCI successful 194
PCI unsuccessful 3
Safety 201
7-day 201
30-day 197
4 patients lost to f/u
6-month 190
11 patients lost to f/u
Ed. 4/19
CADILLAC
• Comparison with CADILLAC entry criteria and
efficacy prespecified in protocol
• CADILLAC, 2082 AMI patients, 2x2 factorial
design (PTCA or stent with and without
abciximab)
• Abciximab/stent group (n=524) used as
comparison
– Highest % TIMI 3 flow rate end of procedure
– Lowest composite endpoint at 30 days and 6 months
G. Stone M.D., C. Grines M.D., D. Cox M.D.
N Engl J Med, Vol. 346, No. 13 March 28, 2002
Patient Characteristics
CADILLAC Comparison
BIAMI
Abciximab/Stent
(N=201)
(N=524)
60
59
Weight, Kg
86.0
-
Male sex, %
69.2
74.0
Diabetes mellitus, %
16.9
16.2
Current smoking, %
46.3
42.0
Prior infarction, %
9.0
13.0
Prior percutaneous intervention, %
11.4
11.8
Prior bypass surgery, %
3.0
1.9
Prior stroke or transient ischemic
attack, %
4.0
2.9
Left ventricular ejection fraction,
Median
0.47
0.50
Age, yr
Target Vessel/
Lesion Characteristics
BIAMI
Abciximab/
Stent
%
%
35.0
18.3
45.7
33.8
19.3
46.9
(N=197)
Infarct Vessel
Left anterior descending coronary artery
Left circumflex artery
Right coronary artery
Target Lesion
A
B1
B2
C
VISIBLE THROMBUS
(N=524)
%
4.2
14.1
39.3
42.4
60.9
na
na
na
na
na
Ed 5/9
PCI Therapy
Stents
–Drug Eluting Stents
n
123
– Cypher 69
– Taxus 64
–Bare Metal Stents
–Drug Eluting and Bare Metal
–Thrombectomy
54
10
16
Anticoagulation
– All patients received bivalirudin during
their PCI
• 60% of patients received UFH before their
intervention
• 40% of patients received NO UFH, only bivalirudin
• NO significant bleeding occurred in the patient
population that received BOTH UFH and
bivalirudin
• Mean ACT 189 seconds in patients who received
UFH.
Concomitant Meds
Clopidogrel
Prior to Enrollment
Prior to PCI
After PCI
%
12.4
44.2
43.4
Concomitant Meds
• Abciximab bolus and infusion
n/N
%
– Administration for less than
TIMI-3 flow post procedure
20/197
10.1
12/20
60.0
– TIMI-3 flow achieved
post-Abcixmab
Of the 194 patients with a successful PCI,
86 required post-procedure anticoagulation:
Angiomax®
64 patients
Heparin
14 patients
Both
8 patients
Post Procedure Heparin (non CABG)
Heparin
(N=22)
Unfractionated heparin
IABP
Low molecular weight heparin
Reasons for heparin continuation
•
•
•
•
IABP
Transition to Warfarin
DVT / PE prophylaxis
Other
17
11
5
Post Procedure Angiomax®
(non CABG)
Angiomax
(N=72*)
Dose
Duration, median
0.25 mg/kg/hr
4 hrs
* Only 25 patients had greater than 30 minutes Angiomax
Pre/Post-Procedure TIMI Flow
Pre-TIMI Flow
Post-TIMI Flow
(N=197)
(N=197)
%
%
TIMI 0
63.5
0.5
TIMI 1
12.2
1.0
TIMI 2
16.2
5.1
TIMI 3
8.1
93.4
* Visible Thrombus present prior to procedure in
61.2% of patients.
Ed 4/21
Primary Endpoint
7-Day
(N=201)
%
30-Day
(N=196)
%
6-Month
(N=190)
%
2.5
4.1
8.9
Death
1.0
2.0
3.7
Reinfarction
0.5
1.0
3.2
Ischemic TLR
Stroke*
0.5
0.5
1.5
1.0
4.2
1.0
1.0
1.0
Efficacy
Ischemic Composite
Subacute Thrombosis**
* Both strokes post CABG
** SAT not collected to 6 months
Ed. 5/9
Efficacy 30 days: Patient Details
60 yr
Female
No
No Heparin For IABP BMS
post primary
(2.0 x 13mm)
procedure
Experienced chest pain 5 days post PCI
Heparin post procedure for IABP
No abciximab.
Angiography revealed SAT to previously
placed stent in LAD.
Repeat stent LAD/RCA.
Revascularization
Death
#14004
PCI
1 day
83 yr
Female
No
No Angiomax
4 stents in index
(low dose 4 hrs) vessel
2 BMS
Post primary
procedure
2 Cypher
Staged procedure.
Post PCI. 3VD, BMS & Cypher
(4 stents) in LAD.
Next day PTCA in LAD, stents in RCA.
Acute anterior wall MI with 3VD
PCI of all 3 vessels
Death secondary to CHF
Revascularization
#07004
CABG
19 days
72 yr
Male
No
No Abciximab
IC – NTG
Ant-LAT MI
Cypher 2 LAD/DIAG
Recath next day
Residual disease LAD/Ischemia 19 days
later - CABG
Pre Clop
PCI
5 days
DM
Reinfarction
Revascularization
Age
Endpoint
Revasc
Proc/
Days
post
primary
PCI
Concomitant
Meds
Infarct
lesion stent
Subacute
Thrombosis
#01005
Cypher
(3.0 x 28)
(2.5 x 18)
Narrative
03/23
Efficacy 30 days: Patient Details
contd.
Pre Clop
DM
Age
Endpoint
Revasc
Proc/
Days post
primary
PCI
Infarct
Concomitant
lesion stent
Meds
Narrative
Revascularization
Stroke
#1011
CABG
22 days
66 yr
Female
No
No
-
BMS
(3.0 x 24)
No post procedure anticoag
Presented with ischemia
Stroke
#10003
CABG
2 days
63 yr
Male
Yes
No
-
Taxus
(3.0 x 20)
Heparin for CABG and 15 days
for ventrical apical thrombus
Subacute
Thrombosis
#2013
Planned
PCI
2 days
70 yr
Male
No
Yes
-
Taxus
(3.5 x 24)
Finding of SAT in primary lesion
when undergoing PCI for 2nd
lesion in staged procedure
03/23
Deaths at 30 days : Patient Details
Pre Clop
DM
Age
Endpoint
Days
post
primary
PCI
Cardiac
Death
2 days
89 yr No
Female
No
Cardiac
Death
2 days
77 yr Yes Yes
Female
Non Cardiac
Death
26 days
78 yr No
Female
Cardiac
Death
30 days
83 yr No
Female
Concomitant
Meds
Infarct
lesion
stent
Narrative
Angiomax for 6 1 Cypher Death – arrest 2nd day post
hrs
3.0 x 13mm procedure
3 VD
LAD
Abciximab
Cypher
Diabetic.
Remained hypotensive post
procedure
Death – multisystem organ
failure.
No
-
2 BMS
3x13
3.5x 3.5
COPD, hypertension.
Anemia prior to index procedure.
2VD
Readmitted with lower GI
bleeding. Death – cardiac arrest.
No
Angiomax
continued
Low dose
Multiple
Anterior wall MI
3 VD. Two procedures, stents in
all 3 vessels.
Death – complications of CHF.
Bleeding Endpoint
Safety
7-Day
(N=201)
%
Clinically Significant Bleed
3.0
Blood Product Transfusion
2.5
Intracranial Hemorrhage
0.0
Thrombocytopenia
1.5
i. Abciximab & IABP
ii. IABP Bleed
ii. No PCI / on table arrest
#9002
#12005
#6003
– All bleeds had post procedural anticoagulation
Ed 5/9
Clinically Significant Bleeding : Details
All bleeds had post procedural anticoagulation/antiplatelet
Age
85
Gender
Hgb g/dL Clopidogrel
Decrease
Prior
Site
Tx
Post Procedure Meds
Female
Groin hematoma
Yes
No
Yes
Abciximab
Female
None identified
Yes
3.3
No
Angiomax 4.2 hrs.
Female
None identified
Yes
3.9
2.2
Yes
Angiomax 4 hrs, no PCI
Delayed PCI with Heparin
Heparin continued 7 hrs post PCI
Transfusion post PCI
Female
None identified
Yes
1.8
No
Angiomax 4 hrs
post index for persistent thrombus
Female
Pseudoaneurysm No
5.0
Yes
Angiomax 4 hrs
post index procedure
Female
Retroperitoneal
4.7
No
Heparin post procedure
#07011
78
#14013
79
#14012
82
#07002
64
#14018
45
Yes
#1046
Ed 04/21
30-Day Clinical Outcomes
Comparison to CADILLAC
BIAMI
(N=196)
Abciximab/Stent
(N=524)
30-Days
%
%
Ischemic Composite
4.1
4.4
Death
2.0
2.7
Reinfarction
1.0
0.8
Ischemic TLR
1.5
Disabling Stroke
1.0*
1.6
0.2
* Two Strokes Post CABG
Ed. 5/9
6-Month Clinical Outcomes
Comparison to CADILLAC
BIAMI
(N=190)
Abciximab/Stent
(N=524)
%
%
8.9
10.2
Death
3.7
4.2
Reinfarction
3.2
2.2
Ischemic TLR
4.2
5.2
Disabling Stroke*
1.0
0.4
6-Months
Ischemic Composite
* Two Strokes Post CABG
Ed. 4/18