Heart Failure Risk in Patients with Diabetes, Hypertension or Myocardial Infarction

1
Background and baseline
Frans J Van de Werf MD PhD Professor and
Chairman Department of Cardiology University
Hospital Gasthuisberg Leuven, Belgium
2
New fibrinolytics
mortality at 4 weeks(major fibrinolytic RCTs)
GUSTO I 19901993
GUSTO III 19951997
ASSENT-2 19971998
InTIME-II19971998
tPA
nPA
3
Aspirin in acute MI
ISIS-2
20
15
13.2
35-day mortality ()
10
10.7
10.4
8.0
5
4300
4300
4295
4292
0
placebo
ASA
SK
SKASA
ISIS-2. Lancet 19882(8607)349-360
4
GP IIb/IIIa blockade
resting platelet GP IIb/IIIa ligand-incompetent
inhibition of platelet aggregationby GP IIb/IIIa
blockade
GP IIb/IIIa antagonist
agonist (ADP, thrombin, epi)
fibrinogen
activated platelet GP IIb/IIIa ligand-competent
aggregating platelets fibrinogen occupies GP
IIb/IIIa, forming bridges between adjacent
platelets
aggregating platelets fibrinogen occupies GP
IIb/IIIa, forming bridges between adjacent
platelets
Lefkovits J, et al. N Engl J Med
19953321553-1559
5
Pilot trials of abciximab in AMI
6
TIMI 14
abciximab and tPA in acute MI
100
tPAabciximab
80
tPA
79
71
69
60
62
61
90-minute TIMI 3 flow ()
58
54
53
40
abciximab 0.30 mg/kg
38
20
146
36
40
50
28
46
34
36
31
0
bol inf(60)
bol inf(30)
bol inf(60)
bol inf(60)
acceler tPA
bol
bol
bol inf(30)
bol
100 mg
20 mg
35 mg
50 mg
65 mg
7
Abciximab and fibrinolysis
abciximab improves myocardialreperfusion TIMI
14 trial
100
tPA alone
80
abciximabreduced-dose tPA
69
60
of patients with complete(gt70) ST resolution
p0.0004
59
p0.001
40
44
37
20
n125
n221
n80
n151
0
all patients
patients with TIMI 3 flow at 90 minutes
de Lemos JA, et al. Circulation 2000101239-243
8
SPEED
abciximab and reteplase in acute MI
dose-confirmation phase(core laboratory
assessment)
100
TIMI 3
TIMI 2
80
21.6
28.7
60
patency ()
54.9
40
47.5
20
n115
n109
0
rPA 55 Uabciximab
rPA 1010 U
9
Trial design
abciximab and low-dose reteplase in acute MI
randomization
standard-dose reteplase (1010 U double bolus)
abciximab reduced-dose reteplase (55 U double
bolus)
heparin 5000 U 1000 U/h (800 U/hr for lt70 kg)
heparin 60 U/kg (max 5000 U) 7 U/kg/h
primary endpoint 30-day death
10
Treatment regimens
11
Endpoints
primary 30-day mortality (all-cause) secondary mor
tality (30-day) or non-fatal disabling
stroke(in-hospital or 7-day) hemorrhagic stroke
(in-hospital or 7-day) mortality by 1 year
reinfarction coronary revascularization other
prespecified complications of MI
12
Pre-specified statistical methods
superiority testing 1-sided type I errorlt2.5 for
control mortality rates ranging from
59 approximately 80 power to detect 15
reduction if control mortality rate7.4 non-infer
iority testing defined as less than 10 relative
increase in mortality (ie upper bound of 95 CI
for relative risk?1.10) 1-sided type I error
ranges from 2.0512.627 for control mortality
rates ranging from 59 interim
analyses conducted by SEMC at 1000, 2500, 5000,
8300, and 12 450 patients enrolled Lans-DeMets
stopping criteria
13
Demographics
14
Risk factors
15
Enrollment event
16
Medications
17
Heparin