Washout of long-term treatment with flecainide and propafenone in patients with complex ventricular arrhythmias and cardiac disease

Abstract To assess the spontaneous variability of ventricular arrhythmias after withdrawal of apparently successful antiarrhythmic therapy, we enrolled in a washout protocol 40 patients who had completed a randomized controlled 2-year study of antiarrhythmic drugs (the Antiarrhythmic Drug Evaluation Group [ADEG] study). All of them had heart disease and were first seen with high-grade ventricular arrhythmias (Lown class 4a and 4b) at enrollment. After 2 years all of them had responded to propafenone or flecainide; patients who completed the study on a regimen of amiodarone were not considered for the washout study. A total of 27 patients discontined flecainide and 13 propafenone. Seven days after withdrawal they underwent 24- or 48-hour ECG testing and were classified as true responders (TR) if the arrhythmias were present at the same level as 2 years previously and false responders (FR) if they were below the ADEG responsiveness level. TR patients had a third 24-hour ECG 7 days later, after rechallenge with the same treatment, and FR patients had a third ECG without drugs. Adherence to the protocol was ascertained by measuring drug plasma concentrations at every 24-hour ECG recording. No differences were found in distribution of heart disease and grade of ventricular arrhythmias between patients in the washout study and the remaining group of the ADEG trial. Twenty-four of 40 patients (60%) were true responders. In 4 of the 17 patients who had a third 24 hour ECG, the responsiveness to the same drug was not confirmed. Sixteen of 40 patients were false responders (40%); in all but 1 of 15 patients who had a third 24-hour ECG, the FR status was confirmed. No difference was found between FR and TR patients with regard to heart disease, basal level of ventricular arrhythiias, echo parameters at enrollment, number of drugs changed during the ADEG trial, and last drug taken. Long-term variability of ventricular ectopic beats, couplets, and runs ≥3 consecutive beats (ratio between log of arrhythmic events in washout and enrollment 24-hour ECGs) was significantly higher in FR patients. Our data suggest that an average proportion of patients with heart disease and complex ventricular arrhythmias has a spontaneous reduction of the same arrhythmias over 2 years. No variables predictive of this behavior were found. A periodic reassessment of arrhythmic patterns after drug washout is therefore needed and, as shown, is feasible.