DENVER (EGMN) – The investigational intravenous antiarrhythmic agent vernakalant proved superior to amiodarone for conversion of recent-onset atrial fibrillation in the European AVRO trial.

The rate of conversion to sinus rhythm within 90 minutes – the primary study end point – was 10 times greater with vernakalant than with intravenous amiodarone. Moreover, vernakalant proved safe and well tolerated, Dr. A. John Camm reported at the annual meeting of the Heart Rhythm Society.

AVRO (A Phase III Superiority Study of Vernakalant vs. Amiodarone in Subjects With Recent Onset Atrial Fibrillation) involved 232 adults with symptomatic AF of 3-48 hours duration. For 29% of participants, it was their first-ever episode of the arrhythmia; at the other extreme, 34% had more than three prior episodes.

Participants received either a 10-minute infusion of vernakalant at 3 mg/kg followed, if needed after a 10-minute observation period, by an additional 10-minute infusion at 2 mg/kg; or a 60-minute infusion of amiodarone at 5 mg/kg followed by a maintenance infusion of 50 mg given over 60 minutes.

The conversion rate to sinus rhythm within the first 90 minutes was 51.7% with vernakalant compared with 5.2% with amiodarone. Twenty-four percent of patients in the vernakalant group converted within 10 minutes and 42% within 25 minutes, compared with 0.9% and 2.6%, respectively, in the amiodarone group. The median time to conversion among vernakalant responders was 11 minutes.

Nearly 54% of the vernakalant group had no AF symptoms at 90 minutes, compared with 33% of the amiodarone group. Patients’ perception of well-being measured 2 hours after the start of infusion was significantly greater in the vernakalant group as reflected in a mean 10.9-point improvement from a baseline of 66 on the EQ-5D quality of life visual analog scale, compared with a 5.6-point improvement with amiodarone, reported Dr. Camm of St. George’s University of London.

Side effects associated with vernakalant were mainly mild and transient nausea, cough, and sneezing. One patient developed short, nonsustained ventricular tachycardia. There were no cases of ventricular fibrillation, torsades de pointes, or sustained or polymorphic ventricular tachycardia.

Audience members griped that amiodarone was something of a straw man as a comparator. Why not choose a faster-acting currently available agent such as ibutilide or procainamide? The answer, Dr. Camm explained, is that AVRO was conducted in response to a European Medicines Agency request for additional data to assist in its regulatory decision making. In the European countries where the trial was conducted, neither ibutilide nor procainamide is universally available and amiodarone is considered the current standard of care. A request for marketing approval for vernakalant is also under review at the U.S. Food and Drug Administration.

丹佛(EGMN)——欧洲的AVRO试验显示，试验用静脉内抗心律失常制剂维那卡兰(vernakalant)对新发心房颤动(AF)的转复效果优于胺腆酮。

 

维那卡兰组90min内的窦性心律转复率——此项研究的主要终点——是静脉用胺腆酮组的10倍多。此外，研究证实维那卡兰安全性和耐受性良好，A. John Camm博士在心律协会年会上报告说。

 

AVRO(“比较维那卡兰和胺腆酮对新发房颤转复效果的III期优势临床试验”)纳入了232例房颤症状持续3~48h的成年患者。其中有29%是首次出现此型心律失常，而34%的患者以前出现过3次以上。

 

这些研究对象或者应用维那卡兰3mg/kg输注10min，在10min观察期后，如有必要，再以2mg/kg的剂量输注10min；或者应用胺腆酮5mg/kg输注60min，然后再用50mg维持输注60min以上。

 

维那卡兰组在第一个90min内窦性心律的转复率是51.7%，胺腆酮组是5.2%。维那卡兰组有24%的患者在10min内转复，42%的患者在25min内转复；而胺腆酮组以上数据分别为0.9%和2.6%。维纳卡兰有效者的中位转复时间是11min。

 

在第90min时，维那卡兰组近54%的患者房颤症状消失，胺腆酮组33%。维那卡兰组开始输注后2h患者的满意度明显强于胺腆酮组，表现为EQ-5D生活质量视觉模拟量表(VAS)评分从基线时的66分平均提高10.9分，与之相比，胺腆酮组提高了5.6分。伦敦大学圣乔治学院的Camm博士报告说。

 

维那卡兰的不良反应主要是一过性的轻微恶心、咳嗽和喷嚏。有一例患者出现了短暂的非持续性室性心动过速。未出现心室颤动、尖端扭转型或持续性或多型性室性心动过速病例。

 

与会者认为将胺腆酮拿来做比较多少有些挡箭牌的意味。为什么不选择诸如伊布利特(ibutilide)或者普鲁卡因胺(procainamide)这样现今可用且起效快的药物进行比较？Camm博士解释说：AVRO是应欧洲药品管理局需要更多资料来协助进行决策的要求进行的。在进行此试验的欧洲国家，伊布利特和普鲁卡因胺尚未得到普遍应用，而胺腆酮被视为当前治疗的标准药物。美国食品药品管理局也在审核维那卡兰的上市许可申请。

 

AVRO试验的资金来自Cardiome制药公司。Camm博士透露说他是此公司的顾问，并为其进行有报酬的演讲工作。

 

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