Antiarrhythmic actions of amiodarone: a profile of a paradoxical agent

Amiodarone, a complex compound with variegated electropharmacologic and pharmacokinetic properties and an equally complex side-effect profile, continues to have a critical role in the control of ventricular and supraventricular tachyarrhythmias as the use of class I agents has declined. Such is also the case with sotalol. Unlike other so-called class III agents, amiodarone non-competitively blocks sympathetic stimulation, and its effects on repolarization are not associated with reverse use dependency. Rarely does it produce torsades de pointes despite its propensity to induce significant bradycardia and marked prolongation of the QT interval. During long-term therapy with the drug, there is no impairment of ventricular function; in fact, there are significant increases in the left ventricular ejection fraction during protracted amiodarone therapy in patients with heart failure. Long-term amiodarone administration consistently demonstrates marked efficacy in a wide spectrum of arrhythmias. The major limitation of amiodarone during long-term therapy is its unusual side-effect profile, although the increasing trend for low-dose drug therapy has demonstrated a major decline in the overall incidence of serious adverse reactions. Amiodarone is effective in controlling symptomatic ventricular tachycardia and fibrillation (VT/VF) in > 60-70% of patients when conventional agents (especially class I) are ineffective or not well tolerated. The efficacy of amiodarone compared with that of an implantable cardioverter-defibrillator in patients with VT/VF and in survivors of cardiac arrest remains uncertain when total mortality is used as the primary endpoint of comparison. Amiodarone suppresses ventricular ectopy and markedly suppresses nonsustained VT. It prevents inducible VT/VF in a small number of patients, but slows VT rate in a larger number. The role of the drug in prolonging survival in the postmyocardial infarction patient is unclear, although preliminary data from blinded studies suggest that the drug decreases arrhythmia-related mortality. Similarly, in heart failure, amiodarone has the potential to reduce total mortality but appears to be selectively effective in nonischemic rather than in ischemic cardiomyopathy. Intravenous amiodarone was recently introduced in the United States for the control of recurrent destabilizing VT or VF resistant to conventional therapy. There is also evolving data indicating that the drug might be the most potent agent in maintaining sinus rhythm in patients with atrial fibrillation or flutter converted chemically or electrically to sinus rhythm. However, blinded controlled comparative studies involving sotalol, quinidine, or pure class III drugs have not been carried out. The available data nevertheless suggest that, barring its side-effect profile, amiodarone is a desirable prototype of a broad-spectrum antifibrillatory and antiarrhythmic compound.