J Clin Pharmacol
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First published on January 7, 2009, doi:10.1177/0091270008329549

The Journal of Clinical Pharmacology 2009;49:312.

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©© 2009 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology, 10.1177/0091270008329549


Article

Rapid Conversion of Persistent Atrial Fibrillation to Sinus Rhythm by Intravenous AZD7009

J. Christoph Geller 1*, Kenneth Egstrup 2, Piotr Kulakowski 3, Mårten Rosenqvist 4, Maria Aunes Jansson 5, Anders Berggren 5, Nils Edvardsson 5, Philip Sager 5, and Harry J. Crijns 6

1 Zentralklinik, Bad Berka
2 Svendborg Sygehus, Denmark
3 Grochowski Hospital, Warszaw
4 Södersjukhuset, Stockholm
5 AstraZeneca, Sweden and United States
6 Academic Hospital, Maastricht

* To whom correspondence should be addressed. E-mail: c.geller.kar{at}zentralklinik-bad-berka.de.


   Abstract
This randomized, double-blind trial compared cardioversion rates between AZD7009 infusion (15-minute 3.25 mg/min, 15-minute 4.4 mg/min, or 30-minute 3.25 mg/min) and placebo infusion (15 or 30 minutes) in patients with atrial fibrillation (AF) scheduled for DC cardioversion. One hundred sixty-eight patients were randomized, 167 received study treatment, and 159 were included in perprotocol analyses. The mean duration of current AF episode was 47 days (range, 0.892). In the AZD7009 30-minute 3.25 mg/min group, 21 of 42 patients converted within 90 minutes, compared with 7 of 39, 7 of 36, and 0 of 42 patients in the 15-minute 3.25 mg/min, 15-minute 4.4 mg/min, and combined placebo groups, respectively. Patients not converted within 90 minutes underwent DC cardioversion. In patients with AF episodes ≤30 days, conversion rates with AZD7009 30-minute 3.25 mg/min and after placebo followed by DC cardioversion were 82% and 83%, respectively. AZD7009 was generally well tolerated. Mean QTc increased by 15% to 20% in the AZD7009 treatment groups. One patient experienced a ventricular tachyarrhythmia of 7 beats, with features of torsades de pointes. AZD7009 was associated with a 50% conversion rate in the best-dose group. In patients with AF episodes ≤30 days, the conversion rates after AZD1305 and placebo followed by DC cardioversion were observed to be similar.
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