A multicentre, randomized trial on the benefit/risk profile of amiodarone, flecainide and propafenone in patients with cardiac disease and complex ventricular arrhythmias

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 andfollowedfor 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 At 2 years 18 patients haddied (9/18 suddenly), 19 had withdrawn because of major clinical events or severe ADR, 13 had dropped out, seven hadbeen non-responders throughout the entire sequence of drugs, whereas eight were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 thefirst drug. Median exposure time to amiodarone, 518 days . patienr', was higher than for flecainide and propafenone, 218 and 178, respectively, indicating better overall response to amiodarone (P<001). A total of50 ADRs led to drug with-drawal, with cardiovascular ADR being less frequent (P<003) 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% couldbe obtainedin theshort-term (7–28 days) and54% at 2years. Amiodarone has a morefavourable therapeutic profile than flecainide and propafenone in these patients, having less tendency to worsen heartfailure.