From TheHeart.org, 17 May 2010 (Heart Rhythm Society Annual Conference, Denver)
Denver, CO – The use of vernakalant (Merck/Cardiome Pharma) is more effective than amiodarone for the rapid conversion of atrial fibrillation (AF) to sinus rhythm and is associated with a higher rate of symptom relief, according to the results of a new study . Vernakalant was shown to be safe and well tolerated and was also associated with greater improvements in quality of life.
The results of the study, known as the AVRO trial, were presented by Dr A John Camm (St George’s University, London, UK) during the late-breaking clinical-trials session here at the Heart Rhythm Society 2010 Scientific Sessions.
As reported earlier by heartwire, vernakalant is a novel intravenous pharmacologic agent developed for the acute conversion of AF. The drug works by blocking early-activating K+ channels and frequency-dependent Na+ channels. In the Atrial Arrhythmia Conversion Trial I (ACT I) trial, also reported by heartwire, researchers showed that the antiarrhythmic agent successfully converted more patients to normal sinus rhythm than placebo.
Speaking during the late-breaking clinical-trials session, Camm said that the AVRO study, a randomized, double-blind, multicenter superiority trial, was requested by the European Medicines Agency and was conducted in patients with underlying structural heart disease, making certain antiarrhythmic drugs inappropriate for use. For that reason, amiodarone, which is widely available across Europe where the study was conducted, was selected as the comparator agent.
Still not approved by the FDA
In total, 254 adult patients with AF were enrolled in the study, with 116 patients in each group receiving at least one dose of the study drug. Approximately 30% of patients in both treatment arms had no AF episodes prior to the initial diagnosis, whereas one-third had three or more episodes. For treatment, those in the vernakalant study arm received a 10-minute infusion of 3 mg/kg followed by an additional 10-minute infusion of 2 mg/kg if needed after a 15-minute observation period. Amiodarone patients received a 60-minute infusion of 5 mg/kg followed by an additional 60-minute maintenance infusion of 50 mg.
Regarding the primary end point of the study, the proportion of patients in sinus rhythm at 90 minutes, 51.7% of patients were converted from AF to sinus rhythm in the vernakalant arm, compared with just 5.2% of those in the amiodarone arm (p<0.0001). Treatment with vernakalant resulted in a rapid conversion to sinus rhythm, with a median conversion time of 11 minutes. For the secondary end point, 53% of patients treated with vernakalant were without AF symptoms at 90 minutes, compared with 33% of the amiodarone-treated patients. Significant improvements in quality-of-life scores were also reported among the vernakalant-treated patients.
Camm noted that among the vernakalant-treated patients there was an atrial thrombus detected by imaging, chest pain diagnosed as angina pectoris by the attending clinician, an episode of syncope, and some tingling regarded as sensitivity to the drug. There were no reported cases of torsades de pointes, ventricular fibrillation, sustained ventricular tachycardia, or drug-related deaths. Side effects reported were those primarily related to nausea as well as a distorted sense of taste, cough, and sneezing.
“All of these symptoms were transient and were not seen after the two-hour period,” said Camm.
In December 2007, vernakalant cleared one regulatory hurdle when a Food and Drug Administration advisory panel voted six to two in favor of making the drug available. Despite the vote for approval, some concerns were raised about the use of vernakalant in the setting of hypotension, as well as in certain subgroups, such as patients with heart failure or an acute coronary syndrome. The FDA has since requested more information on the drug, and it is still not approved in the US.