[Intermediary and substitution criteria in the development of anti-arrhythmia agents].

The traditional view that the suppression of arrhythmias (risk factor) after myocardial infarction can only be beneficial, has been queried by the results of the Cardiac Arrhythmia Suppression Trial (CAST) which showed increased mortality in two treatment groups. The methodology of trials of secondary prevention of myocardial infarction by antiarrhythmic agents partially explains why the reduction of anti-arrhythmias has come to be considered as a substitute for mortality in the assessment of drug efficacy. The authors define substitutive criteria and describe their three advantages (facility, correspondence, estimation). A meta-analysis of 6 trials of secondary prevention of myocardial infarction by Class I antiarrhythmics, in which the antiarrhythmic effect was evaluated (Holter monitoring) in parallel with mortality, shows that anti-arrhythmias were significantly reduced by nearly 60% (p = 10-8) whereas mortality remained unchanged (p = 0.41). A special graphic presentation of the results of these 6 trials shows that, even before the results of the CAST, it was clear that the suppression of antiarrhythmics was not a suitable substitutive end point for mortality.