Abstract 3697: RSD1235 Effectively Converts Atrial Fibrillation to Sinus Rhythm Independent of Background Use of Oral Rate- or Rhythm-Control Medications
Background: The efficacy and safety of intravenous RSD1235, a novel, early-activating K+ and frequency-dependent Na+ channel blocker, in converting atrial fibrillation (AF) to sinus rhythm (SR) were evaluated in 2 multicenter, placebo (PBO)-controlled Atrial Arrhythmia Conversion Trials (ACT I and ACT III). A pooled analysis from ACT I and ACT III, which assessed RSD1235 based on patients’ use of background oral rate- or rhythm-control medication and AF duration (3 h to 7 d and 3 h to 45 d), is reported.
Methods: Patients with AF lasting 3 h to 45 d were randomly assigned to RSD1235 3 mg/kg or PBO infused over 10 min, followed by a 15-min observation period. A second 10-min infusion of RSD1235 2 mg/kg or PBO was given if AF did not terminate. The primary efficacy measure was the percentage of patients who demonstrated conversion to SR for at least 1 min within 90 min of dosing. Background medication (BM) consisted of any rate- or rhythm-control medication taken during the 7-d period before the study.
Results: Of 575 patients receiving treatment (mean age, 62 y; 68% were male), 390 had AF lasting 3 h to 7 d. The percentage of BM use was similar in patients in both AF duration groups (Table⇓). Overall, the rate of AF-to-SR conversion was significantly higher with RSD1235 than with PBO in patients with AF lasting 3 h to 7d (51.1% vs 3.8%; P<.0001) and lasting 3 h to 45 d (36.9% vs 3%; P<.0001). Conversion of AF to SR with RSD1235 was not affected by use of beta-blockers or calcium channel blockers. RSD1235 was numerically more efficacious in patients taking sotalol and numerically less efficacious in those taking digoxin or class I or III antiarrhythmics. Because the numbers of patients taking these BMs were small, definite conclusions regarding the differences in efficacy with these BMs are uncertain. Use of BM did not affect the incidence of adverse events.
Conclusion: RSD1235 effectively converts AF lasting 3 h to 7 d or 3 h to 45 d to SR in patients who used background oral rate- or rhythm-control medication.