Injection of the investigational agent vernakalant can rapidly convert short-duration atrial fibrillation to sinus rhythm, according to an article in the March 25 issue of Circulation.

The phase III Atrial arrhythmia Conversion Trial (ACT I) enrolled hemodynamically stable patients with symptomatic atrial fibrillation or nontypical atrial flutter; it was conducted at 44 sites in Canada, the United States and Scandinavia. The study assessed the safety and efficacy of vernakalant for the conversion of the dysrhythmia.

The efficacy and safety evaluable populations included 220 patients in the short-duration atrial fibrillation group and 116 patients in the long-duration atrial fibrillation group. Patients were randomized in a 2:1 ratio to vernakalant 3 mg/kg or placebo infused over 10 minutes. After 15 minutes, a second 10-minute infusion of drug or placebo was given if the dysrhythmia persisted or atrial flutter was present.

Primary efficacy measure was the percentage of patients demonstrating conversion to sinus rhythm for at least one minute within 90 minutes of dosing in the short-duration dysrhythmia group.

The researchers found that 75 of 145 (51.7 percent) patients with short-duration dysrhythmia (defined as 3 hours to 7 days) converted to sinus rhythm within 90 minutes compared with 3 of 75 (4.0 percent) of placebo patients.

The subgroup of vernakalant patients whose atrial fibrillation had lasted 3 to 48 hours had the highest conversion rate (62.1 percent) compared with 4.9 percent with placebo. The median time to conversion to sinus rhythm for the 75 patients receiving vernakalant who converted was 11 minutes. Only 1 of the 75 drug-treated patients who converted to sinus rhythm relapsed to dysrhythmia at 24 hours.

The most common adverse events reported within the first 24 hours in drug-treated patients were taste disturbance (29.9 percent), sneezing (16.3 percent), skin sensation (10.9 percent), nausea (9 percent), and hypotension (6.3 percent). These events were generally self-limited. Four serious adverse events possibly or probably related to drug treatment occurred in three patients and included hypotension (2 events), complete atrioventricular block, and cardiogenic shock.

"Due to the importance of treating atrial fibrillation quickly, we're pleased that vernakalant displayed such a rapid conversion of atrial fibrillation to sinus rhythm," said Edward Pritchett, MD, Consulting Professor of Medicine, Divisions of Cardiology and Clinical Pharmacology, Duke University Medical Center and consultant for Astellas Pharma US, the drug's manufacturer.