Safety and efficacy of intravenously administered tedisamil for rapid conversion of recent-onset atrial fibrillation or atrial flutter.

Abstract

OBJECTIVES:

The goal of the present study was to assess the efficacy and safety of intravenous tedisamil, a new antiarrhythmic compound, for conversion of recent-onset atrial fibrillation (AF) or atrial flutter (AFL) to normal sinus rhythm (NSR).

BACKGROUND:

Tedisamil is a novel antiarrhythmic drug with predominantly class III activity. Its efficacy and safety for conversion of recent onset AF or AFL to NSR is not known.

METHODS:

This was a multicenter, double-blind, randomized, placebo-controlled, sequential ascending dose-group trial. A total of 201 patients with symptomatic AF or AFL of 3 to 48 h duration were enrolled in a two-stage study. During stage 1, patients were randomized to receive tedisamil at 0.4 mg/kg body weight or matching placebo; during stage 2, patients received tedisamil at 0.6 mg/kg body weight or matching placebo. Treatments were given as single intravenous infusions. The primary study end point consisted of the percentage of patients converting to NSR for at least 60 s within 2.5 h.

RESULTS:

Of 175 patients representing the intention-to-treat sample, conversion to NSR was observed in 41% (25/61) of the tedisamil 0.4 mg/kg group, 51% (27 of 53) of the tedisamil 0.6 mg/kg group, and 7% (4/59) of the placebo group (p < 0.001 for both tedisamil groups vs. placebo). Average time to conversion was 35 min in patients receiving tedisamil. There were two instances of self-terminating ventricular tachycardia: one episode of torsade de pointes and one of monomorphic ventricular tachycardia, both in patients receiving 0.6 mg/kg tedisamil.

CONCLUSIONS:

Tedisamil at dosages of 0.4 and 0.6 mg/kg was superior to placebo in converting AF or AFL. Tedisamil has a rapid onset of action leading to conversion within 30 to 40 min in the majority of responders.

• Authors: Stefan H Hohnloser, Paul Dorian, Matthias Straub, Katrin Beckmann, Peter Kowey
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 44 Issue 1 Pg. 99-104 (Jul 07 2004) ISSN: 0735-1097 [Print] United States
• PMID: 15234416 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Arrhythmia Agents
• Bridged Bicyclo Compounds, Heterocyclic
• Cyclopropanes
• tedisamil

Topics

• Aged
• Aged, 80 and over
• Anti-Arrhythmia Agents (administration & dosage)
• Atrial Fibrillation (drug therapy, mortality, physiopathology)
• Atrial Flutter (mortality, physiopathology, therapy)
• Bridged Bicyclo Compounds, Heterocyclic (administration & dosage)
• Combined Modality Therapy
• Cyclopropanes (administration & dosage)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Electric Countershock
• Electrocardiography
• Endpoint Determination
• Female
• Heart Conduction System (drug effects, physiopathology)
• Humans
• Injections, Intravenous
• Male
• Middle Aged
• Survival Analysis
• Treatment Outcome