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Atrial Fibrillation (AF) is the most common arrhythmia requiring treatment in the emergency department and admission to the hospital. Early conversion of AF to sinus rhythm improves symptoms and prevents the detrimental effects of prolonged AF. However the number of drugs available to convert AF is modest and they are associated with a number of adverse effects. One of the promising new drugs for pharmacological cardioversion is Vernakalant. It blocks early activating K+ channels (IKur) and frequency-dependent Na+ channels. It is relatively atrial selective therefore its effects are more pronounced in the fibrillating atria than the ventricles.
Camm et al. (1) report the results of the AVRO trial (A Phase III Superiority Study of Vernakalant vs Amiodarone in Subjects With Recent Onset Atrial Fibrillation), which was a multicenter, randomized, blinded phase III clinical study comparing the investigational drug vernakalant with amiodarone for conversion of new-onset AF >3 h but <7 days in duration. They studied a total of 254 adult patients with AF eligible for cardioversion. Patients received either a 10-min infusion of vernakalant (3 mg/kg) followed by a 15-min observation period and a second 10-min infusion (2 mg/kg) if still in AF, plus a sham amiodarone infusion, or a 60-min infusion of amiodarone (5 mg/ kg) followed by a maintenance infusion (50 mg) over an additional 60 min, plus a sham vernakalant infusion. Some of the exclusion criteria were acute decompensated heart failure and acute coronary syndromes.
The study shows a conversion rate of 52% within 90 min when vernakalant was administered compared with 5% for amiodarone (p<0.0001). Vernakalant also resulted in rapid conversion (median time of 11 min in responders) and was associated with a higher rate of symptom relief compared with amiodarone. Although there were no cases of torsades de pointes, ventricular fibrillation, or polymorphic or sustained ventricular tachycardia, 8.6% of patients in the vernakalant arm converted from AF to atrial flutter.
In summary this study shows that vernakalant provides a superior and safe alternative to amiodarone for the acute conversion of recent-onset AF. It appears to have a low incidence of inducing ventricular arrhythmias. The high conversion rate would also facilitate early discharge of patients from emergency department. Although the results of this trial are encouraging further trials are needed to prove its safety in patients with more extensive heart disease.
1. Camm AJ, Capucci A, Hohnloser SH, Torp-Pedersen C, Van Gelder IC, Mangal B, Beatch G;
AVRO Investigators. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation.
J Am Coll Cardiol. 2011 Jan 18;57(3):313-21.
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