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Electrophysiologic profile and efficacy of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with sustained monomorphic ventricular tachycardia

Yaves Bashir, Poul-Erik B Thomsen, J Herre Kingma, Mogens Møller, Christopher Wong, Stuart M Cobbe, Luc Jordaens UGent, Ronald WF Campbell, Henrik S Rasmussen and A John Camm (1995) AMERICAN JOURNAL OF CARDIOLOGY. 76(14). p.1040-1044
abstract
There is increasing evidence that class III antiarrhythmic agents may be superior to class I agents for the long-term treatment of life-threatening ventricular tachyarrhythmias. This open study evaluated he acute electrophysiologic effects, antiarrhythmic efficacy, and safety of different doses of intravenous dofetilide, a new dass III drug, in 50 patients with sustained monomorphic ventricular tachycardia inducible by programmed electrical stimulation who had previously been unsuccessfully treated with 0 to 7 (median 3) other drugs. Intravenous dofetilide was administered over 60 minutes at he following dose levels: 1.5, 3.0, 6.0, 9.0, and 15.0 mu g/kg. Significant class III activity was apparent at doses of 3.0 to 15.0 mu g/kg, as evidenced by dose-related prolongation of the QTc interval by 13.4% to 14.2%, ventricular effective refractory period by 7.9% to 20.6%, and ventricular functional refractory period by 7.3% to 25.0%. The corresponding mean +/- SD plasma dofetilide concentrations ranged from 1.45 +/- 0.52 to 6.48 +/- 1.31 ng/ml, There was no evidence of reverse use-dependence. At these electrophysiologically active dose levels, intravenous dofetilide suppressed (complete response) or slowed (partial response) inducible ventricular tachycardia in 17 of 41 patients (41%) compared with 0 of 9 patients receiving only 1.5 mu g/kg. The response rate was fairly uniform among the groups receiving 3.0, 6.0, 9.0, and 15.0 mu g/kg. Intravenous dofetilide was hemodynamically well tolerated, Torsades de pointes (which was self-limiting) developed in only 1 patient, who was allocated to receive 15.0 mu g/kg. There were no other proarrhythmic episodes or serious adverse effects. Further evaluation of the therapeutic potential of dofetilide in the management of life-threatening ventricular arrhythmias is justified.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
AGENT, TACHYARRHYTHMIAS, THERAPY, POSITIVE INOTROPY, ANGINA-PECTORIS, INFARCTION, TRIALS, POTENT
journal title
AMERICAN JOURNAL OF CARDIOLOGY
Am. J. Cardiol.
volume
76
issue
14
pages
1040 - 1044
Web of Science type
Article
ISSN
0002-9149
DOI
10.1016/S0002-9149(99)80293-8
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
196051
handle
http://hdl.handle.net/1854/LU-196051
date created
2004-01-14 13:42:00
date last changed
2016-12-19 15:39:00
@article{196051,
  abstract     = {There is increasing evidence that class III antiarrhythmic agents may be superior to class I agents for the long-term treatment of life-threatening ventricular tachyarrhythmias. This open study evaluated he acute electrophysiologic effects, antiarrhythmic efficacy, and safety of different doses of intravenous dofetilide, a new dass III drug, in 50 patients with sustained monomorphic ventricular tachycardia inducible by programmed electrical stimulation who had previously been unsuccessfully treated with 0 to 7 (median 3) other drugs. Intravenous dofetilide was administered over 60 minutes at he following dose levels: 1.5, 3.0, 6.0, 9.0, and 15.0 mu g/kg. Significant class III activity was apparent at doses of 3.0 to 15.0 mu g/kg, as evidenced by dose-related prolongation of the QTc interval by 13.4\% to 14.2\%, ventricular effective refractory period by 7.9\% to 20.6\%, and ventricular functional refractory period by 7.3\% to 25.0\%. The corresponding mean +/- SD plasma dofetilide concentrations ranged from 1.45 +/- 0.52 to 6.48 +/- 1.31 ng/ml, There was no evidence of reverse use-dependence. At these electrophysiologically active dose levels, intravenous dofetilide suppressed (complete response) or slowed (partial response) inducible ventricular tachycardia in 17 of 41 patients (41\%) compared with 0 of 9 patients receiving only 1.5 mu g/kg. The response rate was fairly uniform among the groups receiving 3.0, 6.0, 9.0, and 15.0 mu g/kg. Intravenous dofetilide was hemodynamically well tolerated, Torsades de pointes (which was self-limiting) developed in only 1 patient, who was allocated to receive 15.0 mu g/kg. There were no other proarrhythmic episodes or serious adverse effects. Further evaluation of the therapeutic potential of dofetilide in the management of life-threatening ventricular arrhythmias is justified.},
  author       = {Bashir, Yaves and Thomsen, Poul-Erik B and Kingma, J Herre and M{\o}ller, Mogens and Wong, Christopher and Cobbe, Stuart M and Jordaens, Luc and Campbell, Ronald WF and Rasmussen, Henrik S and Camm, A John},
  issn         = {0002-9149},
  journal      = {AMERICAN JOURNAL OF CARDIOLOGY},
  keyword      = {AGENT,TACHYARRHYTHMIAS,THERAPY,POSITIVE INOTROPY,ANGINA-PECTORIS,INFARCTION,TRIALS,POTENT},
  language     = {eng},
  number       = {14},
  pages        = {1040--1044},
  title        = {Electrophysiologic profile and efficacy of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with sustained monomorphic ventricular tachycardia},
  url          = {http://dx.doi.org/10.1016/S0002-9149(99)80293-8},
  volume       = {76},
  year         = {1995},
}

Chicago
Bashir, Yaves, Poul-Erik B Thomsen, J Herre Kingma, Mogens Møller, Christopher Wong, Stuart M Cobbe, Luc Jordaens, Ronald WF Campbell, Henrik S Rasmussen, and A John Camm. 1995. “Electrophysiologic Profile and Efficacy of Intravenous Dofetilide (UK-68,798), a New Class III Antiarrhythmic Drug, in Patients with Sustained Monomorphic Ventricular Tachycardia.” American Journal of Cardiology 76 (14): 1040–1044.
APA
Bashir, Y., Thomsen, P.-E. B., Kingma, J. H., Møller, M., Wong, C., Cobbe, S. M., Jordaens, L., et al. (1995). Electrophysiologic profile and efficacy of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with sustained monomorphic ventricular tachycardia. AMERICAN JOURNAL OF CARDIOLOGY, 76(14), 1040–1044.
Vancouver
1.
Bashir Y, Thomsen P-EB, Kingma JH, Møller M, Wong C, Cobbe SM, et al. Electrophysiologic profile and efficacy of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with sustained monomorphic ventricular tachycardia. AMERICAN JOURNAL OF CARDIOLOGY. 1995;76(14):1040–4.
MLA
Bashir, Yaves, Poul-Erik B Thomsen, J Herre Kingma, et al. “Electrophysiologic Profile and Efficacy of Intravenous Dofetilide (UK-68,798), a New Class III Antiarrhythmic Drug, in Patients with Sustained Monomorphic Ventricular Tachycardia.” AMERICAN JOURNAL OF CARDIOLOGY 76.14 (1995): 1040–1044. Print.