Vernakalant Hydrochloride Is Effective In Conversion To Normal Heart Rhythm
Normal Heart Rhythm
Investigational agent of Astellas Pharma US vernakalant hydrochloride increased conversion to normal heart rhythm (sinus rhythm, or SR) in patients with atrial fibrillation (AF) following coronary artery bypass graft (CABG) or valvular surgeries. AF is a potentially serious condition characterized by an irregular heart rhythm and a high heart rate. The study results were presented at the annual meeting of the American Heart Association.
"Postoperative AF is common after cardiac surgery, occurring in up to 40% of patients and has a significant effect on both the intensive care unit and overall hospital length of stay," said Peter Kowey, MD, William Wikoff Smith Chair in Cardiovascular Research at the Main Line Health System. "This study shows that vernakalant may be an effective treatment option for converting AF to SR following CABG or valvular surgeries."
The Atrial arrhythmia Conversion Trial or ACT II was a randomized, double-bind, placebo-controlled, parallel-group, multinational, multicenter study evaluating the efficacy and safety of vernakalant among patients who experienced AF or atrial flutter within 24 hours to 7 days after cardiac surgery.
Patients received vernakalant 3 mg/kg (n=107) or placebo (n=54) infused over 10 minutes. After 15 minutes, a second 10 minute infusion of vernakalant 2 mg/kg or placebo was given if AF or atrial flutter was present. The primary efficacy measure was the percentage of patients with treatment-induced conversion of AF/atrial flutter to SR for at least one minute within 90 minutes.
Patients demonstrating conversion within 90 minutes were categorized as responders. Other efficacy measures included time to conversion of all responders and percentage of AF patients demonstrating conversion to SR within 90 minutes for one minute.
Following CABG or valvular surgery, a significantly higher percentage of patients with AF/atrial flutter given vernakalant (45 percent) demonstrated conversion to SR within 90 minutes compared to patients given placebo (15 percent), p=.0002. In the subset of patients with AF at baseline, conversion was observed in 47 percent treated with vernakalant compared with 14 percent given placebo, p=.0001. Median time to conversion among vernakalant responders was 12 minutes and SR was maintained for patients with AF/atrial flutter for 24 hours in 60 percent and for seven days in 57 percent. Seventy-five percent of vernakalant responders required only one dose of drug. Vernakalant is not effective in atrial flutter.
The most common adverse events (AEs) in patients given vernakalant were AF (20 percent), nausea (6 percent), constipation (5 percent), weight increase (5 percent) and dyspnea (5 percent). Rates of serious AEs over the entire study were similar with placebo (11 percent) and vernakalant (9 percent). In the first 24 hours, only 2 patients (2 percent) given vernakalant experienced a serious AE (complete AV block and hypotension). There were no deaths or cases of torsade de pointes.