Author + information
- Received December 1, 2003
- Revision received February 10, 2004
- Accepted March 16, 2004
- Published online July 7, 2004.
- Stefan H. Hohnloser, MD*,* (, )
- Paul Dorian, MD†,
- Matthias Straub, MD‡,
- Katrin Beckmann‡ and
- Peter Kowey, MD§
- ↵*Reprint requests and correspondence:
Dr. Stefan H. Hohnloser, J. W. Goethe University, Department of Cardiology, Division of Electrophysiology, Theodor-Stern-Kai 7, 60596 Frankfurt/Main, Germany.
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.
☆ Sponsored by an unrestricted grant from Solvay Pharmaceuticals. Drs. Hohnloser, Dorain, and Kowey are serving as scientific advisors to Solvay Pharmaceuticals, and Dr. Straub and Mrs. Beckmann are employees of Solvay Pharmaceuticals.
- Received December 1, 2003.
- Revision received February 10, 2004.
- Accepted March 16, 2004.
- American College of Cardiology Foundation