Transcript Results following EM

Clinical Trial Commentary
PACT
MUSTT
Dr Eric Topol
Chairman and Professor, Department of Cardiology
Director of the Joseph J Jacobs Center for Thrombosis
and Vascular Biology at the Cleveland Clinic
Dr Robert Califf
Professor of Cardiology
Associate Vice Chancellor for
Clinical Research at Duke University
PACT trial
Plasminogen-activator Angioplasty
Compatibility Trial





multicenter, randomized, double-blind trial
606 AMI patients
< 75 years old, low-risk infarctions
50 mg IV bolus of rtPA vs placebo
followed by rescue PTCA if TIMI-3 flow not
immediately achieved
Ross AM, et al. J Amer Coll Cardiol 1999;34:1954-1962
PACT trial
Reperfusion and LV function:
rtPA vs placebo
rtPA
(n=302)
Frequency of TIMI-3 flow
33%
immediately following drug treatment
Placebo
(n=304)
15%
LVEF immediately following drug
treatment
59.4%±13.81 57.7%±14.12
Frequency of TIMI-3 flow achieved
following rescue PTCA
78.6%3
1
2
3
4
80.5%4
ventriculograms available for analysis for only 220 patients
ventriculograms available for analysis for only 224 patients
in 169 patients with TIMI 0, 1, or 2 flow following drug treatment
in 231 patients with TIMI 0, 1, or 2 flow following drug treatment
Ross AM, et al. J Amer Coll Cardiol 1999;34:1954-1962
PACT trial
Adverse clinical outcomes:
rtPA vs placebo
rtPA
(n=302)
Placebo
(n=304)
Recurrent ischemia*
17.9%
13.5%
Reinfarction
3.0%
2.6%
Reocclusion†
5.9% (11/187)
3.7% (7/189)
Emergent CABG
2.0%
4.6%
Intracerebral hemorrhage
0.3%
0.3%
30-day mortality
3.6%
3.3%
Rate of major hemorrhaging
12.9%
13.5%
as noted on the patient’s case report form
† angiographically defined
*
Ross AM, et al. J Amer Coll Cardiol 1999;34:1954-1962
PACT trial
“The bottom line is that the combination
therapy did not improve LV function or
change outcome…Enhancing reperfusion
by 10, 15, or 20 minutes hasn’t proven
to be an added benefit. So why would
you adopt that type of therapy?”
Dr Cindy Grines
William Beaumont Hospital, Detroit
PACT trial ignites clash of opinions…
heartwire. theheart.org. December 2, 1999.
MUSTT trial eligibility criteria
• EF < 40%
• CAD
• spontaneous nonsustained
ventricular tachycardia (VT-NS)
Eligible patients randomized to
• electrophysiologic (EP)-guided
antiarrhythmic therapy
• no antiarrhythmic therapy
Buxton AE, et al. N Engl J Med 1999;341:1882-1890
MUSTT:protocol
Electrophysiologic studies
Registry
(n=1435)
Randomization
(n=704)
sustained VT
not inducible
sustained VT
inducible
Conservative
therapy (n=353)
EP-guided therapy
(n=351)
ACE-inhibitors and
beta-blockers
ACE-inhibitors and
beta-blockers
Buxton AE, et al. N Engl J Med 1999;341:1882-1890
MUSTT results
EP guided therapy showed a reduction in
primary endpoints
 27% reduction in arrhythmic death and
cardiac arrest
 trend toward overall reduction in mortality
(20% risk reduction)
 entire benefit derived from EP-guided therapy
was due to treatment with implantable
defibrillators
Buxton AE, et al. N Engl J Med 1999;341:1882-1890
MUSTT and implantable defibrillators
Benefit was derived from implantable
defibrillators, however:
 trial was not designed to test efficacy of
ICD therapy
 patients were not randomized to receive
ICD implantation
 ICD was only undertaken after patients
failed antiarrhythmic drug therapy
A second look at the Multicenter UnSustained
Tachycardia Trial (MUSTT). Clinical trials.
theheart.org. December 7, 1999.
Sudden Cardiac Death in Heart Failure
Trial (SCD-HeFT): randomization
Control group
Heart failure Rx
Blinded placebo
Amiodarone group
Heart failure Rx
Blinded amiodarone
ICD group
Heart failure Rx
Single-lead, pectoral ICD
SCD-HeFT eligibility criteria
•
EF < 35%
•
CHF treatment with ACE-I > 3 months
•
NYHA II and III, ischemic or nonischemic
•
Age > 18 years
• projected enrollment 2 500
• minimum 2.5 year follow-up
SCD-HeFT endpoints
Primary endpoint:
overall mortality
Secondary endpoints:
1. arrhythmic vs nonarrhythmic cardiac
mortality
2. comparison of morbidity
3. comparison of quality of life
4. analysis of cost effectiveness
5. categorizing arrhythmias in ICD arm
MUSTT trial
“…it is an implantable device. But if we
had these results in a study looking at
aspirin, do you really think we'd be
sitting here arguing over would I
withhold aspirin therapy from a defined
sub-risk group…what we're really
talking about here is economics, that's
the bottom line.”
Dr Eric Prystowski
St Vincent Hospital
A second look at the Multicenter UnSustained
Tachycardia Trial (MUSTT). Clinical trials.
theheart.org. December 7, 1999.
CABG Patch trial eligibility criteria
•
EF < 36%
•
scheduled for CABG
•
abnormalities on signal averaged ECG’s
•
Age < 80 years
• patients (n=900) randomly assigned to ICD
vs control
• average follow-up 32 + 16 months
Bigger J, et al. New Engl J Med 1997;337:1569-75.
CABG Patch results
Mortality by treatment arm in the CABG Patch trial
ICD group
(n=446)
Control group
(n=454)
Hazard ratio
p value
Overall mortality*
101
95
p=0.64
Cardiac deaths
71
72
-
* primary endpoint
Bigger J, et al. New Engl J Med 1997;337:1569-75.