[Antiarrhythmic agents: current situation].

Abstract

Cardiac Arrhythmia Suppression Trial (CAST) had a profound impact on the practice of cardiology. This trial showed the importance of placebo controls in judging the effects of therapy and the pitfalls of using surrogate end points for mortality in clinical disorders. The number of new prescriptions of class I drugs fell progressively after CAST; there was a change in antiarrhythmic drug labelling as well as on research and the "suppression hypothesis" was no more valuable as a theoretical support to the antiarrhythmic treatment of prognostical significant ventricular arrhythmias. Several arguments favour generalization of CAST results to the whole class I drugs. So, all those drugs depress cardiac conductivity, which is potentially arrhythmogenic, and the results of several trials and overviews are in consonance with CAST ones. Beta-blockers are the sole drugs that consistently decreased cardiac sudden death after myocardial infarction. An ancillary study from CAST trial suggests that those drugs can have also an anti-proarrhythmic effect, which needs further confirmation. Beta-blockers can join an important place in malignant ventricular arrhythmias therapy, used lonely or specially in association with drugs from other classes. CAST conclusions are probably not applicable to class III drugs, as they do not depress conductivity, acting mainly by prolonging repolarization. So, they are the most promising drugs in post CAST era: some trials seem to confirm the advantages of amiodarone and DL-sotalol in clinical use, and there are several other new class III drugs in development. A few little and medium dimension amiodarone trials showed a decrease in mortality in myocardial infarction survivors and in patients with cardiac insufficiency. We are waiting the results of some large trials to get more definitive conclusions. In malignant ventricular arrhythmias, empiric amiodarone have been superior to electrophysiological guided therapy. Also in malignant ventricular arrhythmias, DL-sotalol was significantly best than six class I drugs in the prevention of new arrhythmias, the therapy being guided by Holter monitoring or electrophysiological studies. We conclude that in the present state of our knowledge, the greatest promise might hold in the area of complex molecules with a diversity of electrophysiological actions, seeming critical the existence of a sympathicolitic effect for an effective protection against sudden death.