Pause-dependent polymorphic ventricular tachycardia during long-term treatment with dofetilide: a placebo-controlled, implantable cardioverter-defibrillator-based evaluation

Alexander Mazur; Mark E Anderson; Sharon Bonney; Dan M Roden

doi:10.1016/S0735-1097(01)01106-8

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Pause-dependent polymorphic ventricular tachycardia during long-term treatment with dofetilide: a placebo-controlled, implantable cardioverter-defibrillator-based evaluation

Journal article

Open access

Peer reviewed

Pause-dependent polymorphic ventricular tachycardia during long-term treatment with dofetilide: a placebo-controlled, implantable cardioverter-defibrillator-based evaluation

Alexander Mazur, Mark E Anderson, Sharon Bonney and Dan M Roden

Journal of the American College of Cardiology, Vol.37(4), pp.1100-1105

03/15/2001

DOI: 10.1016/S0735-1097(01)01106-8

PMID: 11263615

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Abstract

To compare the incidence of pause-dependent polymorphic ventricular tachycardia (PVT) in patients with implantable cardioverter-defibrillators (ICDs) randomly assigned to the QT-prolonging antiarrhythmic dofetilide or placebo. Drug-related torsade de pointes (TdP) is usually recognized within days of initiating therapy, but its incidence during long-term therapy is unknown. We assessed the frequency of TdP and ICD electrograms compatible with TdP in a multicenter study that randomized ICD patients to placebo (n = 87) or dofetilide (n = 87). As reported elsewhere, the number of patients with a primary trial end point (ICD intervention for VT or ventricular fibrillation) was similar in the two groups. For this analysis, a qualifying event was TdP (on electrocardiogram) or an intracardiac electrogram showing pause-dependent PVT. A total of 620 electrograms obtained in 131 patients were analyzed blindly by prospectively defined criteria for episodes of pause-dependent polymorphic VT. These were identified in 15/87 (17%) patients receiving dofetilide and 5/87 (6%) patients on placebo (p < 0.05). Five of these episodes were early (<3 days), all of which were TdP on dofetilide. There were 15 late events, 10 on dofetilide and five on placebo (p = 0.29). The median time to a late event was 22 days (range 6 to 107 days) for dofetilide and 99 days (range 34 to 207 days) for placebo. Pause-dependent PVT was more common among patients receiving dofetilide, although total VT incidence was similar in the two groups. These data suggest that in ICD patients either long-term dofetilide therapy is associated with an increased risk of TdP or the drug alters VT morphology.

Arrhythmias, Cardiac - therapy

Double-Blind Method

Humans

Middle Aged

Tachycardia, Ventricular - chemically induced

Torsades de Pointes - chemically induced

Male

Anti-Arrhythmia Agents - therapeutic use

Arrhythmias, Cardiac - drug therapy

Sulfonamides - therapeutic use

Anti-Arrhythmia Agents - adverse effects

Phenethylamines - adverse effects

Defibrillators, Implantable

Phenethylamines - therapeutic use

Tachycardia, Ventricular - diagnosis

Electrocardiography

Sulfonamides - adverse effects

Female

Torsades de Pointes - diagnosis

Details

Title: Subtitle: Pause-dependent polymorphic ventricular tachycardia during long-term treatment with dofetilide: a placebo-controlled, implantable cardioverter-defibrillator-based evaluation
Creators: Alexander Mazur - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Mark E Anderson
Sharon Bonney
Dan M Roden
Resource Type: Journal article
Publication Details: Journal of the American College of Cardiology, Vol.37(4), pp.1100-1105
DOI: 10.1016/S0735-1097(01)01106-8
PMID: 11263615
NLM abbreviation: J Am Coll Cardiol
ISSN: 0735-1097
eISSN: 1558-3597
Grant note: HL46681 / NHLBI NIH HHS HL03727 / NHLBI NIH HHS HL49989 / NHLBI NIH HHS
Language: English
Date published: 03/15/2001
Academic Unit: Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984094775402771

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