Key result
Mixture model reconciles discordant trial outcomes between MADIT and CABG Patch defibrillator trials.
Why the study?
The CABG Patch Trial showed no mortality benefit from implantable defibrillator placement despite a similar patient population to MADIT, which showed a mortality reduction, motivating exploration of differences in VT inducibility.
May reconcile discrepant ICD trial results; leaves open whether missing data explain CABG Patch null findings.
The Multicenter Automatic Defibrillator Implantation Trial (MADIT) showed a conclusive 54 per cent reduction in mortality in patients with inducible sustained monomorphic ventricular tachycardia (VT) and impaired left ventricular function who received an implantable defibrillator compared with those who did not. The Coronary Artery Bypass Graft (CABG) Patch Trial, which studied a patient population with a similar extent of left ventricular dysfunction and overall cardiovascular risk, demonstrated no mortality benefit from placement of an implantable defibrillator. All patients in the MADIT trial were 'VT inducible', while this criterion was neither required nor evaluated for entry into the CABG Patch Trial. A statistical approach to estimating with good accuracy the fraction of CABG Patch patients who were inducible at the time of their randomization from the prevalence of VT inducibility in the surviving CABG Patch Trial control population during follow-up is presented. This more generally applicable approach estimates the mixing percentage using missing data techniques. We present the mathematical and physiological basis of the assumptions underpinning the mixture model and its estimation procedure. The mixture model forms the basis for the electrophysiological substudy to the CABG Patch Trial, which directly tests the hypothesis that the difference in the frequency of inducible VT between the MADIT and CABG Patch patients populations is sufficient to account for the difference in effect on mortality.
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Rottman et al. (1999) studied impaired left ventricular function and cardiovascular risk. Missing data techniques (mixture model) was evaluated. A statistical mixture model using missing data techniques was proposed to explain why implantable defibrillators reduced mortality by 54% in MADIT but showed no benefit in the CABG Patch Trial.
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