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European Heart Journal 2001 22(23):2180-2191; doi:10.1053/euhj.2001.2679
Copyright © 2001 by the European Society of Cardiology.
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A multicentre, double-blind randomized crossover comparative study on the efficacy and safety of dofetilide vs sotalol in patients with inducible sustained ventricular tachycardia and ischaemic heart disease

G. Boriania,f1, A. Lubinskib, A. Capuccic, P. Niederled, Z. Kornacewicz-Jacke, A.M. Wnuk-Wojnarf, M. Borggrefeg, J. Brachmannh, M. Biffia and G.S. Butrousi on behalf of Ventricular Arrhythmias Dofetilide Investigators

a Istituto di Cardiologia, Università di Bologna, Bologna, Italy
b II Klinica Chorob Serca, Academii Medyczency Gdansku, Gdansk, Poland
c Divisione di Cardiologia, Ospedale Civile, Piacenza, Italy
d Na Homolce, Prague, Czech Republic
e Department of Cardiology, Pomerian Medical Academy, Szczecin, Poland
f Institut Kardiologii, Slaskiej Academii Medyczenej, Klinica Kardiologii, Katowice, Poland
g Inner Medizin, Wesfalische Wilhelms, Universitat, Munster, Germany
h Klinikum der Universitat Heidelberg, Abteilung Kardiology, Heidelberg, Germany
i Pfizer Central Research, Sandwich, U.K.

revised February 20, 2001; accepted February 21, 2001

Abstract

Background Antiarrhythmic drugs are still used for the treatment of ventricular tachyarrhythmias, in combination with implantable cardioverter-defibrillators or without them.

Aim of the study In a double-blind randomized crossover design, the short- and long-term efficacy and safety of oral dofetilide or oral sotalol were compared in 135 patients with ischaemic heart disease and inducible sustained ventricular tachycardia.

Methods The inducibility of ventricular tachycardia was determined by programmed electrophysiological stimulation at baseline. Patients were then blindly randomized to receive either oral dofetilide 500µg twice daily or oral sotalol 160mg twice daily, for 3 to 5 days. Suppression of inducible ventricular tachycardia on the drug was then assessed by programmed electrophysiological stimulation. After a wash-out period of at least 2·5 days, the patients received the alternative treatment for 3 to 5 days. Suppression of inducible ventricular tachycardia on the alternate drug was again determined by programmed electrophysiological stimulation. Selection of long-term treatment was allocated blindly according to programmed electrophysiological stimulation results.

Results During the acute phase, 128 patients received both dofetilide and sotalol. Sixty-seven patients were responders to either drug. Forty-six patients (35·9%) were responders to dofetilide compared with 43 (33·6%) to sotalol (P=ns). Only 23 patients responded to both dofetilide and sotalol. Adverse events, deemed to be treatment related, were seen in 2·3% of patients receiving dofetilide and 8·6% of patients receiving sotalol (P=0·016). Three patients on dofetilide had torsade de pointes. Two patients receiving sotalol died during the acute phase (one was arrhythmic death, and the other was due to heart failure). During the long-term phase, two of 42 patients (4·8%) receiving dofetilide and three of 27 patients (11·1%) receiving sotalol withdrew from treatment due to lack of efficacy. Overall, during the long-term phase, 23·8% of the patients receiving dofetilide and 37·0% of the patients receiving sotalol, withdrew from treatment with a similar pattern of withdrawals for the two drugs.

Conclusion Dofetilide was as efficacious as sotalol in preventing the induction of sustained ventricular tachycardia. There was no concordance in the response rate in two-thirds of the patients. Dofetilide was significantly better tolerated during the acute phase than sotalol. Both dofetilide and sotalol were well tolerated during the long term with no statistically significant difference in the adverse events.

Key Words: Antiarrhythmic agents, dofetilide, sotalol, ventricular tachycardia

f1 Correspondence: Giuseppe Boriani, MD, FESC, Institute of Cardiology, University of Bologna, Policlinico S. Orsola, Via Massarenti 9, 40138 Bologna, Italy.

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