New drug for conversion of AF

MONTREAL, CANADA. Although most atrial fibrillation (AF) episodes experienced by lone afibbers are self-terminating, some do require medical intervention in order to convert to normal sinus rhythm (NSR). Electrical cardioversion has an immediate success rate of about 90%. But only 25-50% of patients remain in NSR for a year. The efficacy is improved if patients are replete in potassium when the conversion is attempted and is very much decreased if the patient is on digoxin (Lanoxin) at the time of the cardioversion.

Pharmacologic conversion is also used and employs intravenous infusions of such drugs as ibutilide (Corvert), flecainide (Tambocor), and propafenone (Rythmol). Although these drugs result in conversion in 30-60% of cases, they must be used with caution as they can cause dangerous ventricular arrhythmias and serious hypotension. A group of researchers from Canada, Scandinavia and the United States completed a phase III clinical trial to evaluate the safety and effectiveness of vernakalant hydrochloride (RSD1235). Vernakalant is an atrium-selective potassium and sodium channel blocker and has, in animal studies, been found to prolong the atrial refractory period.

The clinical trial involved 336 patients enrolled at 44 different centers. The patients were divided into two groups. Group I (220 patients) consisted of AF patients who had been in afib for 3 hours to 7 days, while Group II (116 patients) was made up of those who had been in afib for 8 to 45 days. None of the patients had heart failure (class IV), had experienced a heart attack, or had previously failed electrical cardioversion. They were randomized to receive a 10-minute infusion of vernakalant (3.0 mg/kg) or placebo followed by a 15-minute observation period. If conversion to NSR was not achieved, an additional dose of vernakalant (2.0 mg/kg) or placebo was administered. Patients were then observed in the hospital for a minimum of 8 hours.

Successful conversion was defined as converting to NSR for at least one minute within 90 minutes of the initiation of drug infusion. In Group I (short-duration AF), 51.7% of patients were successfully converted as compared to 4% in the placebo group. Most (76%) of those who converted with vernakalant did so with a single dose and within a median time of 11 minutes. All but one of the 75 patients who converted remained in NSR for more than 24 hours. The success rate in Group II was much lower at 7.9% among vernakalant-infused patients, and 0% among those receiving placebo.

There was a clear trend for the procedure to be more successful the shorter time the patient had been in afib. Thus, those who were treated no more than 48 hours from the onset of their episode experienced a 62.1% conversion rate versus 4.9% with placebo. Overall, 83 of the 221 patients (37.6%) given vernakalant successfully converted versus 2.6% in the placebo group. There were no reports of torsade de pointes or ventricular fibrillation during the first 24 hours after infusion; however, three patients did develop serious adverse events (hypotension and heart block) probably related to vernakalant administration. Minor adverse effects included impaired sense of taste experienced by almost 30% of patients treated with vernakalant, sneezing experienced by 16%, nausea by 9%, and hypotension by 6.3%.

The researchers conclude that vernakalant is safe and effective for conversion of short-duration atrial fibrillation. NOTE: This study was sponsored by the manufacturer of vernakalant, and 8 of the 13 authors had received financial compensation form the manufacturer and/or other pharmaceutical companies.

Roy, D, et al. Vernakalant hydrochloride for rapid conversion of atrial fibrillation. Circulation, Vol. 117, March 25, 2008, pp. 1518-25

Editorís comment: Vernakalant would appear to be a useful drug for intravenous, pharmacological conversion of short-duration afib. However, it does require a trip to the ER so most lone afibbers would likely be better off using the pill-in-the-pocket approach (with flecainide or propafenone), which has a conversion effectiveness around 90%.