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 Placebo (n=302) (n=304) Frequency of TIMI-3 flow 33% 15% immediately following drug treatment LVEF immediately following drug 59.4%±13.81 57.7%±14.12 treatment Frequency of TIMI-3 flow achieved 78.6%3 80.5%4 following rescue PTCA 1 ventriculograms available for analysis for only 220 patients 2 ventriculograms available for analysis for only 224 patients 3 in 169 patients with TIMI 0, 1, or 2 flow following drug treatment 4 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 Placebo (n=302) (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 Randomization (n=1435) (n=704) sustained VT sustained VT not inducible inducible Conservative EP-guided therapy therapy (n=353) (n=351) ACE-inhibitors and ACE-inhibitors and beta-blockers 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 Control group Hazard ratio (n=446) (n=454) 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.
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