The FINESSE Trial:

(Facilitated INtervention
with Enhanced Reperfusion
Speed to Stop Events)
Summary of the results presented by
Stephen Ellis at the European Society
of Cardiology 2007 Congress in Vienna
 Rationale
• Primary PCI within 60-90 minutes of medical contact is the
preferred revascularization strategy for STEMI1,2
• Delays with primary PCI are common, particularly when
patient transfer is required
• Door to balloon and total ischemic time have been directly
related to mortality in multiple studies
• Early pharmacologic reperfusion pre-PCI may lead to
myocardial salvage and better long term outcomes3
• Patients with large areas of ischemia presenting early might
be expected to maximally benefit from such an approach

1. Antman et al. Circulation 2004; 110:588-636

2. Van de Werf et al. EHJ 2003; 24:28-66
3. Keeley et al. Lancet 2006; 367:579-588 Adapted from Ellis, Oral presentation ESC 2007
 Major Objectives
Primary: To test if Reteplase/Abciximab Facilitated PCI
is superior to Primary PCI with in lab Abciximab
Cath lab availability Primary PCI with in
uncertain or anticipated delay of lab Abciximab
1 to 4 hours
?
R Abciximab Facilitated
Primary PCI
?
?
Reteplase/Abciximab
Facilitated
Primary PCI
Secondary:
To test if Reteplase/Abciximab is superior to facilitation with Abciximab alone
To test if Abciximab facilitation is superior to Primary PCI with in lab Abciximab
Adapted from Ellis et al. AHJ 2004; 147: e16
 Study Design
Acute ST Elevation MI (or New LBBB) within 6h pain onset
Presenting at Hub or Spoke with estimated time to Cath between 1 and 4 hours

Randomize 1:1:1
Double Blind N=3000 *Only 5U if 75 yr
Double Dummy

Placebo Placebo Reteplase (5U+5U)*

Placebo Abciximab Abciximab

Transfer To Cath Lab

ASA, unfractionated heparin 40U/kg (max 3000U)
or enoxaparin (0.5 mg/kg IV + 0.3 mg/kg SC) – substudy only

Abciximab Placebo Placebo

Primary PCI with Abciximab Infusion (12 h)

Follow up through 90 days and 1 year

Adapted from Ellis et al. AHJ 2004; 147: e16
Primary Endpoint
• The composite at 90 days of
– All cause mortality
– Resuscitated ventricular fibrillation (VF) occurring
> 48 hours after randomization
– Rehospitalization or emergency department
treatment for congestive heart failure (CHF)
– Cardiogenic shock

Adapted from Ellis et al. AHJ 2004; 147: e16

Major Secondary Endpoints

• All Cause Mortality through 90 days

• Complications of MI through 90 days
– Rehospitalization or emergency department
treatment for CHF
– Resuscitated ventricular fibrillation occurring > 48
hours after randomization
– Cardiogenic shock
• % of subjects with ST-segment resolution >70% from
pretreatment baseline when assessed 60-90 minutes
after randomization

Adapted from Ellis, Oral presentation ESC 2007

Safety Endpoints
• Major Safety Endpoints
– Nonintracranial TIMI major or minor bleeding through
discharge or day 7
– Intracranial Hemorrhage (ICH) including hemorrhagic
transformation through discharge or day 7
• Other
– Disabling stroke or ICH through discharge/day 7
– Non-disabling stroke through discharge/day 7
– TIMI major or minor bleeding through discharge/day 7
– Transfusions
– Thrombocytopenia
– AEs and SAEs through discharge/day 7
Adapted from Ellis, Oral presentation ESC 2007
Key Inclusion/ Exclusion Criteria
• Inclusion Criteria
  21 years of age
– Symptom duration ≥ 20 min to 6 hrs
– STEMI or new left bundle branch block (LBBB)
• Exclusion Criteria
– Local inferior infarction in patients aged < 60 years
– Angiography and PCI expected < 60 min or > 4 hrs after
qualifying ECG
– Prohibited medications (eg. planned use of direct thrombin
inhibitor during PCI, use of fibrinolytic or LMWH within 24hrs)
– Contraindications for abciximab (eg: active bleeding, recent
major surgery; history of stroke or TIA within the previous 2
years or any stroke with a residual neurological deficit)
– Protocol-specified ceiling dose of UFH (40 U/kg, 3000 U max.)
or aPTT 70 sec is exceeded before enrollment
Adapted from Ellis et al. AHJ 2004; 147: e16
FINESSE Enrollment (2002-2006):
Projection vs Actual

N=2452

Enrollment
Terminated
Dec 30, 2006

Adapted from Ellis, Oral presentation ESC 2007

Baseline Demographics/Medical History
Primary PCI Abx Reteplase/Abx
with in Lab Abx Facilitated PCI Facilitated PCI
Variable (n = 806) (n = 818) (n = 828)

Age (years, mean) 62.5 61.9 62.6

Gender (% Female) 26% 26% 26%
Race (% Caucasian) 98% 98% 98%
Smoker (past or current) 65% 67% 65%
HTN or Rx’ed HTN 46% 50% 48%
Anterior MI (%) 46% 49% 48%
Diabetes 17% 15% 16%
Prior MI 10% 10% 13%
Killip Class >1 10% 11% 9%
Prior PCI 4% 5% 7%
Prior Stroke 2% 2% 2%
High Risk (Anterior MI,
Age >70, Killip >I or HR >100) 65% 68% 67%
Adapted from Ellis, Oral presentation ESC 2007
Primary Composite Endpoint

10.7%
10.5%
9.8%

Adapted from Ellis, Oral presentation ESC 2007

Major Secondary Endpoints
All Cause Mortality Complications of MI

8.9%
7.5%
5.5% 7.4%
5.2%
4.5%

Adapted from Ellis, Oral presentation ESC 2007

 TIMI Flow in IRA Pre-PCI
% Subjects with TIMI 2/3 (Patency) Pre-PCI
120%
p<0.0001
100%

80% p<0.0001
61%
Percentage

60%
25% TIMI 2
40% 25% 26%

20% 12% 11% 36% TIMI 3

13% 15%
0%
Primary PCI (in lab Abciximab Facilitated Reteplase/Abciximab
Abciximab) (n=790) PCI (n=809) Facilitated PCI (n=815)
Ave Time from First Abciximab Bolus
to Angiogram In Facilitated Groups: 74min 76min
Modified ITT Population with Index PCI: ITT, PCI and any dose of study drug (active or placebo); Investigator assessment

Adapted from Ellis, Oral presentation ESC 2007

 TIMI Flow Post-PCI
% Subjects with TIMI 2/3 Post-PCI
120%
p=0.126
110%
p=0.042
98% 98% 99%
100%
Percentage

7% 8% TIMI 2
7%
90% * *

80%
91% 90% 92% TIMI 3
70%

60%
Primary PCI (in lab Abciximab Facilitated Reteplase/Abciximab
Abciximab) (n=718) PCI (n=746) Facilitated PCI (n=741)
* All p=NS for TIMI 3 flow

Modified ITT Population with Index PCI: ITT, PCI and any dose of study drug (active or placebo); Investigator assessment

Adapted from Ellis, Oral presentation ESC 2007

 ST Segment Resolution (>70%)
at 60-90 Min: Core Lab
% Evaluable Subjects with ST Segment Resolution
100%
p=0.003 p=0.010 p=NS
80% p=0.013 p=0.011
64%
Percentage

57%
60% 51%
44%
36%
40% 31% 33%
23% 24%
20%

0%
All (n=745) Prior to Balloon After Balloon
Inflation (n=525) Inflation (n=154)
Primary PCI with in lab Abciximab (n=242)
Abciximab Facililated PCI (n=257)
Reteplase/Abciximab Facilitated PCI (n=246)

*Half of subjects randomly selected for Core Lab over-read

Adapted from Ellis, Oral presentation ESC 2007

TIMI Major or Minor Bleeding
(nonintracranial) through Discharge/Day7
TIMI Bleeding through Discharge/Day 7
30%
p<0.001 p<0.001
P=0.025
25% P=0.006
P=0.008
P=0.547
20%
Percentage

P=0.141 P=0.025
P=0.127
14.5%
15%
9.7% 10.1%
10% 6.9%
6.0%
4.1% 4.8% 4.3%
5% 2.6%

0%
TIMI Major TIMI Minor TIMI Major or Minor

Primary PCI with In Lab Abciximab (n=795)

Abciximab Facililated PCI (n=805)
Abciximab/Reteplase Facilitated PCI (n=814)

Adapted from Ellis, Oral presentation ESC 2007

Stroke
Stroke through Discharge/Day 7
5%
p=NS p=NS p=NS

4% p=0.218
Percentage

p=0.062
3%
p=0.497
2%
1.0% 1.1%
0.9%
1% 0.6% 0.5% 0.5% 0.5% 0.4%
0.1% 0.0% 0.0% 0.0%
0%
ICH (n=6) Ischemic (n=15) Total Stroke Fatal Stroke
(n=21) (n=3)

Primary PCI with In Lab Abciximab (n=795)

Abciximab Facililated PCI (n=805)
Reteplase/Abciximab Facilitated PCI (n=814)

Adapted from Ellis, Oral presentation ESC 2007

Conclusions
• Neither facilitated PCI strategy tested provided
clinical benefit compared with Primary PCI with in lab
Abciximab
• Reteplase/Abciximab facilitation, and to a lesser
extent Abciximab facilitation, increased bleeding
compared to the in lab administration of Abciximab
• Primary PCI with in lab Abciximab provides a better
benefit:risk profile than the 2 facilitated strategies in
patients with STEMI who can undergo PCI within 4
hours of first medical contact

Adapted from Ellis, Oral presentation ESC 2007