A multicentre, randomized trial on the benefit/risk profile of amiodarone, flecainide and propafenone in patients with cardiac disease and complex ventricular arrhythmias. Antiarrhythmic Drug Evaluation Group (A.D.E.G.).

The long-term benefit/risk profiles of amiodarone, flecainide and propafenone were compared in 141 patients with complex ventricular arrhythmias and cardiac disease, in a trial designed to mimic the clinical decision-making process. The patients were randomized to various sequences of the three drugs, at two dose levels and followed for 2 years. Drug or doses were changed to deal with insufficient reduction of arrhythmias at 24 h ECG or severe adverse drug reaction (ADR). At 2 years 18 patients had died (9/18 suddenly), 19 had withdrawn because of major clinical events or severe ADR, 13 had dropped out, seven had been non-responders throughout the entire sequence of drugs, whereas eight were non-responders only at the last visit. Thus, 76 patients (54%) were responders after 2 years. Of these, 57 were responders for 2 years with the first drug. Median exposure time to amiodarone, 518 days.patient-1, was higher than for flecainide and propafenone, 218 and 178, respectively, indicating better overall response to amiodarone (P less than 0.01). A total of 50 ADRs led to drug withdrawal, with cardiovascular ADR being less frequent (P less than 0.03) for amiodarone (2/11) than for flecainide (13/16) and propafenone (16/23). In conclusion, with sequences of amiodarone, flecainide and propafenone, an overall response rate of 79% could be obtained in the short-term (7-28 days) and 54% at 2 years. Amiodarone has a more favourable therapeutic profile than flecainide and propafenone in these patients, having less tendency to worsen heart failure.

RCT Entities:   Population Interventions Outcomes