Logic and empiricism in the selection of antiarrhythmic agents. The role of drug combinations.

Advances in investigative techniques of cardiac arrhythmias through invasive procedures (clinical electrophysiology) or through ambulatory electrocardiographic monitoring provide a better understanding of the mechanism responsible for these disturbances and a better assessment of therapeutic efficacy. Yet, it cannot be inferred that the selection of antiarrhythmic agents is orientated in all cases by logical reasoning. Too many factors are unknown, especially those regarding the spontaneous mechanism of initiation of clinical arrhythmias. Patient management very often remains mainly empirical. The problem becomes even more complex when dealing with arrhythmias resistant to single-agent therapy. Drug combinations are then used, often successfully, particularly those combining membrane-stabilising agents with amiodarone or beta-adrenergic blocking agents or combining amiodarone with verapamil. Explanations of the efficacy of these combinations at reduced doses become less certain, but it is more important to achieve efficacy than to understand its mechanism, which does not always amount to a simple increase in plasma drug levels. When attempting to determine the reasons behind the theoretically logical selection of an antiarrhythmic agent, it appears that, in spite of advances in electrophysiology and pharmacology, the logic of this selection owes more to chance than to reason. The problem becomes further complicated when drug combinations are to be used which, in clinical practice, are often the therapeutic solution in difficult cases. Advances made in recent years bring up the question of knowing whether or not logic is near to replacing empiricism.