heart care centers of illinois. design –single arm, open label, 13 u.s. centers –patients with...
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Heart Care Centers of IllinoisHeart 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
– SafetyEvaluated 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 SitesJoseph 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
Patients Enrolled201
Safety 201
7-day 201
30-day 1974 patients lost to f/u
ITT 201
PCI unsuccessful 3PCI successful 194Cath Only 4
Enrollment and Follow-up
6-month 19011 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 BIAMI
(N=201)
Abciximab/Stent (N=524)
Age, yr 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
CADILLAC Comparison
Target Vessel/Lesion Characteristics
BIAMI(N=197)
Abciximab/Stent
(N=524)
Infarct Vessel % %
Left anterior descending coronary artery
Left circumflex artery
Right coronary artery
35.0
18.3
45.7
33.8
19.3
46.9
Target Lesion %
AB1B2CVISIBLE THROMBUS
4.214.139.342.460.9
nanananana
Ed 5/9
PCI TherapyStents n
–Drug Eluting Stents 123– Cypher 69– Taxus 64
–Bare Metal Stents 54–Drug Eluting and Bare Metal 10–Thrombectomy 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 12.4
Prior to PCI
After PCI
44.2
43.4
Concomitant Meds
• Abciximab bolus and infusion
– Administration for less than TIMI-3 flow post procedure
– TIMI-3 flow achieved post-Abcixmab
n/N
20/197
12/20
%
10.1
60.0
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
17
11
Low molecular weight heparin 5
Reasons for heparin continuation• IABP • Transition to Warfarin• DVT / PE prophylaxis• Other
Post Procedure Angiomax®
(non CABG)
* Only 25 patients had greater than 30 minutes Angiomax
Angiomax(N=72*)
Dose 0.25 mg/kg/hr
Duration, median 4 hrs
Pre/Post-Procedure TIMI Flow
Pre-TIMI Flow(N=197)
%
Post-TIMI Flow(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
Efficacy7-Day
(N=201)%
30-Day(N=196)
%
6-Month(N=190)
%
Ischemic Composite 2.5 4.1 8.9
Death 1.0 2.0 3.7
Reinfarction 0.5 1.0 3.2
Ischemic TLR 0.5 1.5 4.2
Stroke* 0.5 1.0 1.0
Subacute Thrombosis** 1.0 1.0
* Both strokes post CABG** SAT not collected to 6 months
Ed. 5/9
Efficacy 30 days: Patient Details
Endpoint
Revasc Proc/
Days post primary
PCI
Age
DM
Pre
Clo
p
Concomitant Meds
Infarct lesion stent
Narrative
Reinfarction
Revascularization
Subacute Thrombosis
#01005
PCI
5 days
60 yrFemale
No No Heparin For IABP post primary procedure
BMS
(2.0 x 13mm)Experienced chest pain 5 days post PCIHeparin post procedure for IABPNo 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
(low dose 4 hrs)
Post primary procedure
4 stents in index vessel
2 BMS
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 3VDPCI of all 3 vessels Death secondary to CHF
Revascularization
#07004
CABG
19 days
72 yr
Male
No No Abciximab
IC – NTG
Cypher
(3.0 x 28)
(2.5 x 18)
Ant-LAT MICypher 2 LAD/DIAGRecath next dayResidual disease LAD/Ischemia 19 days later - CABG
03/23
Efficacy 30 days: Patient Details contd.
Endpoint
Revasc Proc/
Days post primary
PCI
Age
DM
Pre
Clo
p
Concomitant Meds
Infarct lesion stent
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
CABG2 days
63 yrMale
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
Endpoint
Days post primary
PCI
Age
DM
Pre
Clo
p
Concomitant Meds
Infarct lesion stent
Narrative
Cardiac Death
2 days 89 yr
Female
No No Angiomax for 6 hrs
1 Cypher
3.0 x 13mm
LAD
Death – arrest 2nd day post procedure
3 VD
Cardiac Death
2 days 77 yr
Female
Yes Yes Abciximab Cypher Diabetic.
Remained hypotensive post procedure
Death – multisystem organ failure.
Non Cardiac Death
26 days 78 yr
Female
No No - 2 BMS
3x13
3.5x 3.5
COPD, hypertension.
Anemia prior to index procedure. 2VD
Readmitted with lower GI bleeding. Death – cardiac arrest.
Cardiac Death
30 days 83 yr
Female
No No Angiomax continued
Low dose
Multiple Anterior wall MI
3 VD. Two procedures, stents in all 3 vessels.
Death – complications of CHF.
Bleeding Endpoint
– All bleeds had post procedural anticoagulation
Safety7-Day
(N=201)
%
Clinically Significant Bleed 3.0
Blood Product Transfusion 2.5
Intracranial Hemorrhage 0.0
Thrombocytopenia 1.5 i. Abciximab & IABP #9002 ii. IABP Bleed #12005 ii. No PCI / on table arrest #6003
Ed 5/9
Clinically Significant Bleeding : Details
Age Gender Site TxHgb g/dLDecrease
ClopidogrelPrior Post Procedure Meds
85#07011
Female Groin hematoma Yes No Yes Abciximab
78#14013
Female None identified Yes 3.3 No Angiomax 4.2 hrs.
79#14012
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
82#07002
Female None identified Yes 1.8 No Angiomax 4 hrs
post index for persistent thrombus
64#14018
Female Pseudoaneurysm No 5.0 Yes Angiomax 4 hrs
post index procedure
45#1046
Female Retroperitoneal Yes 4.7 No Heparin post procedure
All bleeds had post procedural anticoagulation/antiplatelet
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
Reinfarction
Ischemic TLR
Disabling Stroke
2.0
1.0
1.5
1.0*
2.7
0.8
1.60.2
* Two Strokes Post CABG
Ed. 5/9
6-Month Clinical Outcomes Comparison to CADILLAC
BIAMI(N=190)
Abciximab/Stent (N=524)
6-Months % %
Ischemic Composite Death
Reinfarction
Ischemic TLR
Disabling Stroke*
8.93.7
3.2
4.2
1.0
10.24.2
2.2
5.2
0.4
* Two Strokes Post CABG
Ed. 4/18