[Proarrhythmic effects of anti-arrhythmia agents]

Abstract

Antiarrhythmic medications are widely used either at the ventricular or supraventricular level. However, those drugs can induce severe side effects. Actually, antiarrhythmic drugs are paradoxically able to favour the occurrence of new arrhythmias or aggravate the preexisting arrhythmia for which they were indicated. These proarrhythmic effects have been found in 10 to 20% of patients, as evidenced by literature. Moreover, the CAST study showed a significant increase in mortality in patients with non sustained ventricular arrhythmias after myocardial infarction who were treated with either flecainide or encainide, compared to the placebo group. This overmortality seems to be due, in large, to the proarrhythmic effects of antiarrhythmic drugs. Several mechanisms have been evoked, related to the type of antiarrhythmic drug and to the presenting arrhythmia: early post-depolarization due to slow calcium and sodium inward currents in the case of torsades de pointes, facilitation of intraventricular reentries in the case of class 1c antiarrhythmic drugs, facilitation of the ventricular response of atrial arrhythmias. These deleterious effects, that can be very serious, are unpredictable, not toxicity-related and all antiarrhythmic drugs are involved. Their detection appears to be difficult and is based upon ECG, Holter monitoring, treadmill test and possibly electrophysiologic study. The use of antiarrhythmic drugs requires the knowledge of their proarrhythmic effects, the analysis of the benefit-risk ratio--particularly if left ventricular function is impaired--and careful monitoring.