Beatch Gregory N, Mangal Brian
Cardiome Pharma Corp., 1441 Creekside Drive 6th Floor, Vancouver, BC, V6J 4S7, Canada.
PAREXEL International Corp., Lowell, MA, USA.
BMC Cardiovasc Disord. 2016 May 28;16:113. doi: 10.1186/s12872-016-0289-0.
Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with significant health risks. One strategy to mitigate the risks associated with long-term AF is to convert AF to sinus rhythm (SR). This study assessed the efficacy and safety of vernakalant hydrochloride for the pharmacological conversion of AF to SR.
Patients with recent-onset (duration >3 h- ≤ 7 days) symptomatic AF and no evidence or history of congestive heart failure were randomized in a 2:1 ratio to receive vernakalant or placebo. Patients received an infusion of vernakalant (3 mg/kg) or placebo over 10 min, followed by a second infusion of vernakalant (2 mg/kg) or placebo 15 min later if AF had not been terminated. The primary efficacy endpoint was conversion of AF to SR for at least 1 min within 90 min of the start of drug infusion. The primary safety endpoint was a composite of: occurrence of clinically significant hypotension, clinically significant ventricular arrhythmia (including torsades de pointes, ventricular tachycardia or ventricular fibrillation) or death within 2 h of starting the drug infusion.
A total of 217 patients were randomized to receive vernakalant (n = 145) or placebo (n = 72). Of the 129 individuals who received vernakalant, 59 (45.7 %) converted to SR compared with one of the 68 patients (1.5 %) who received placebo (p < 0.0001). Conversion to SR was significantly faster with vernakalant than with placebo (p < 0.0001), and a greater proportion of patients who received vernakalant than those who received placebo reported no AF-related symptoms at 90 min (p = 0.0264). The primary composite safety endpoint was observed in one patient receiving vernakalant and in no patients receiving placebo. In the vernakalant arm, dysgeusia, paraesthesia and sneezing were the most common treatment-emergent adverse events, and three serious adverse events occurred that were considered to be related to study drug.
Vernakalant resulted in rapid cardioversion of recent-onset AF in almost half of the study population and was generally well tolerated. The safety outcomes affirmed the need for careful selection and management of haemodynamically stable candidates for cardioversion.
NCT00989001 .
心房颤动（AF）是一种常见的心律失常，与重大健康风险相关。减轻长期AF相关风险的一种策略是将AF转为窦性心律（SR）。本研究评估了盐酸维纳卡兰将AF转为SR的有效性和安全性。
近期发作（持续时间>3小时至≤7天）的有症状AF且无充血性心力衰竭证据或病史的患者按2:1比例随机分组，接受维纳卡兰或安慰剂治疗。患者在10分钟内输注维纳卡兰（3mg/kg）或安慰剂，若AF未终止，15分钟后再输注一次维纳卡兰（2mg/kg）或安慰剂。主要疗效终点是在药物输注开始后90分钟内AF转为SR至少1分钟。主要安全终点是以下情况的综合：药物输注开始后2小时内发生具有临床意义的低血压、具有临床意义的室性心律失常（包括尖端扭转型室速、室性心动过速或心室颤动）或死亡。
共有217例患者随机接受维纳卡兰（n = 145）或安慰剂（n = 72）治疗。在接受维纳卡兰的129例患者中，59例（45.7%）转为SR，而接受安慰剂的68例患者中有1例（1.5%）转为SR（p < 0.0001）。维纳卡兰使转为SR的速度明显快于安慰剂（p < 0.0001），且接受维纳卡兰的患者中在90分钟时报告无AF相关症状的比例高于接受安慰剂的患者（p = 0.0264）。在接受维纳卡兰的1例患者中观察到主要综合安全终点，接受安慰剂的患者中未观察到。在维纳卡兰组，味觉障碍、感觉异常和打喷嚏是最常见的治疗中出现的不良事件，发生了3例被认为与研究药物相关的严重不良事件。
维纳卡兰使近一半的研究人群中近期发作的AF快速复律，且总体耐受性良好。安全性结果证实了对血流动力学稳定的复律候选者进行仔细选择和管理的必要性。
NCT00989001 。
