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CLINICAL STUDY

Antiarrhythmic effects of azimilide in atrial fibrillation: efficacy and dose-response

Edward L. C. Pritchett, MD^a, Richard L. Page, MD, FACC^*, Stuart J. Connolly, MD, FACC, Stephen R. Marcello, MD, FACC, Daniel J. Schnell, PhD, William E. Wilkinson, PhD the Azimilide Supraventricular Arrhythmia Program 3 (SVA-3) Investigators

^a Department of Medicine, Divisions of Cardiology and Clinical Pharmacology, Duke University Medical Center, Durham, North Carolina, USA
^* Department of Medicine, Cardiovascular Division, University of Texas Southwestern Medical Center, Parkland Memorial Hospital, Dallas, Texas, USA
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Procter and Gamble Pharmaceuticals, Cincinnati, Ohio, USA
Department of Community and Family Medicine, Division of Biometry, Duke University Medical Center, Durham, North Carolina, USA

Manuscript received July 2, 1999; revised manuscript received March 1, 2000, accepted April 13, 2000.

Reprint requests and correspondence: Dr. Edward L.C. Pritchett, Room 04280, Duke South Hospital, DUMC-3477, Durham, North Carolina 27710
ed.pritchett{at}duke.edu

OBJECTIVES

The purpose of this study was to assess the effectiveness of azimilide, a class III antiarrhythmic drug, in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation, atrial flutter or both.

BACKGROUND

Atrial fibrillation is an increasingly common disorder of the heart rhythm, and most patients with this problem are identified because they have symptoms associated with their arrhythmia. New antiarrhythmic therapies are needed to treat patients with this problem.

METHODS

A total of 384 patients with a history of atrial fibrillation, atrial flutter or both were randomly assigned to receive once daily doses of placebo or azimilide; recurrent symptomatic arrhythmias were documented using transtelephonic electrocardiogram (ECG) recording. Azimilide 50 mg, 100 mg or 125 mg was tested; the primary efficacy analysis compared the time to first symptomatic recurrence in the combined azimilide 100 mg and 125 mg dose groups with that in the placebo group using the log-rank test.

RESULTS

In the primary efficacy analysis, the time to first symptomatic arrhythmia recurrence was significantly prolonged in the combined azimilide 100 mg and 125 mg daily dose group compared with the placebo group (chi-square 7.96, p = 0.005); the hazard ratio (placebo:azimilide) for this comparison was 1.58 (95% confidence interval [CI] = 1.15, 2.16). In comparisons between individual doses and placebo, the hazard ratio for the 50 mg daily dose was 1.17 (95% CI = 0.83, 1.66; p = 0.37); for the 100 mg group, dose was 1.38 (95% CI = 0.96, 1.98; p = 0.08), and for the 125 mg group, dose was 1.83 (95% CI = 1.24, 2.70; p = 0.002).

CONCLUSIONS

Azimilide significantly lengthened the symptomatic arrhythmia-free interval in patients with a history of atrial fibrillation, atrial flutter or both.

Abbreviations and Acronyms   AF = atrial fibrillation   BID = twice daily   CI = confidence interval   ECG = electrocardiogram   QD = daily

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