Ну, вот и кордарон побил.
AVRO Published: Vernakalant Beats Amiodarone for New Onset AF Conversion
January 11, 2011 (London, United Kingdom) — Vernakalant (Merck/Cardiome Pharma), a novel intravenous pharmacologic agent that blocks early-activating K+ channels and frequency-dependent Na+ channels, is more effective than amiodarone for the rapid conversion of atrial fibrillation (AF) to sinus rhythm, the AVRO trial results show [1]. In addition, patients treated with vernakalant had significantly greater symptom relief at 90 minutes and a greater perceived feeling of well-being at two hours, report investigators.
The results of the trial, previously presented during the Heart Rhythm Society (HRS) 2010 Scientific Sessions by lead investigator Dr A John Camm (St George's University, London, UK), are now published in the January 18, 2011 issue of the Journal of the American College of Cardiology.
Despite the publication of the AVRO trial, vernakalant remains stuck in regulatory limbo in the US. In December 2007, a Food and Drug Administration advisory panel voted six to two in favor of making the drug available, but vernakalant has not yet been approved because of concerns about hypotension as well as questions about its use in patients with heart failure and acute coronary syndromes. The ACT 5 study, the phase 3 trial specifically requested by the FDA in 2008, has halted enrollment following a single serious case of cardiogenic shock in a patient who received the drug.
To heartwire , a spokesperson for Astellas Pharma US, the company that holds the US rights to vernakalant, confirmed that enrollment in the ACT 5 trial is still on hold, but the company has not changed its projection on the study's date of completion. At present, the earliest results for the primary end point--a composite of hypotension, ventricular arrhythmias, and death verified by the clinical events committee and the successful conversion to normal sinus rhythm for at least one minute--are expected in May 2011.
Vernakalant has been approved for use in the European Union, Iceland, and Norway for the rapid conversion of recent-onset AF to sinus rhythm in adults for nonsurgical patients with AF of duration of seven days or less and for post–cardiac-surgery patients with AF of duration of three days or less.
The AVRO Trial
The AVRO investigators enrolled 254 adult patients with recent-onset AF (duration of three hours to 48 hours) eligible for cardioversion. Individuals randomized to vernakalant 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, the conversion to normal sinus rhythm, 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). At 90 minutes, significantly more patients treated with vernakalant were without AF symptoms when compared with those treated with amiodarone (53% vs 33%, p=0.0012).
Reducing the Cost of Care
In an editorial accompanying the published study, Dr Bruce Lindsay (Cleveland Clinic, OH) points out that 35% of patients included in the AVRO trial had structural heart disease, making the cohort representative of many patients seen with new-onset AF [2]. As Camm noted last year during the HRS late-breaking clinical session, the study was requested by the European Medicines Agency, and amiodarone selected as the comparator agent, because other antiarrhythmic drugs are inappropriate in patients with underlying structural heart disease.
Lindsay noted that amiodarone has a low efficacy for conversion of AF to sinus rhythm and that it is extensively used in the emergency department, telemetry floors, and intensive care unit. Other agents, particularly ibutilide, are not available in all European countries, just as intravenous formulations of flecainide and propafenone are not available in the US, making such comparisons in a clinical trial difficult.
Overall, the vernakalant trials suggest that serious drug-related adverse events occur in about 2% of patients, but the drug does not appear to be associated with a significant risk of torsades de pointes or sustained ventricular arrhythmias, writes Lindsay. "The relatively high conversion rate for new-onset AF would facilitate treatment of patients in the emergency department and could reduce cost of care if patients could be discharged with follow-up in the office as opposed to the need for admission to the hospital," he writes.
The AVRO trial was sponsored by Cardiome Pharma. Camm has received consulting fees from Sanofi-Aventis, Cardiome Pharma, ARYx, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, Astellas, and Merck; research grants from Daiichi, Sanofi-Aventis, Servier, Bristol-Myers Squibb, and Pfizer; and lecture fees from Sanofi-Aventis, St Jude
Medical, Medtronic, Boston Scientific, Boehringer Ingelheim, Merck Sharp & Dohme, and Bristol-Myers Squibb. Disclosures for the coauthors are listed in the paper. Lindsay has received speaker honoraria from Medtronic and has served as a consultant to Biosense Webster, Cardioinsight, and Siemens.
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