A randomized, placebo-controlled study of vernakalant (oral) for the prevention of atrial fibrillation recurrence after cardioversion.

ABSTRACT

BACKGROUND: Vernakalant, a relatively atrial-selective antiarrhythmic drug, has previously demonstrated efficacy for the acute conversion of atrial fibrillation (AF) to sinus rhythm. This study was designed to determine the most appropriate oral dose of vernakalant for the prevention of AF recurrence postcardioversion. METHODS AND RESULTS: Patients with nonpermanent AF were randomized to 150, 300, or 500 mg vernakalant or placebo twice daily for up to 90 days. The efficacy analysis was conducted on 605 of 735 patients who entered the maintenance phase on day 3 after cardioversion. The time to the first recurrence of symptomatic sustained AF was significantly longer in the 500 mg vernakalant group, with a median of >90 days versus 29 days in the placebo group (hazard ratio, 0.735; P=0.0275). No significant effect was seen at the lower doses. The percent of patients in sinus rhythm at day 90 was 41%, 39%, and 49% in the 150-mg (n=147), 300-mg (n=148), and 500-mg (n=150) vernakalant groups, respectively, compared with 36% in the placebo group (n=160). There were no vernakalant-related proarrhythmic events. Related serious adverse events occurred in 2 patients in the 150-mg vernakalant group and in 1 patient in each of the other groups. CONCLUSIONS: Vernakalant, 500 mg twice daily, appears to be effective and safe for the prevention of AF recurrence after cardioversion. The absence of proarrhythmia and favorable safety profile is an important finding for the drug. CLINICAL TRIAL REGISTRATION URL http//www.clinicaltrials.gov. Unique identifier NCT00526136.