Memantine for Premature Atrial Contractions: A Phase 2 Randomized Clinical Trial.

Experimental studies have identified a functional cardiac glutamatergic system in which N-methyl-D-aspartate receptors regulate atrial electrophysiology.

实验研究发现了一种功能性心脏谷氨酸能系统，其中N-甲基-D-天冬氨酸受体调节心房电生理学。

Preclinical studies show that pharmacological antagonism of N-methyl-D-aspartate receptors with memantine suppresses atrial arrhythmias.

临床前研究表明，使用美金刚对N-甲基-D-天冬氨酸受体进行药理拮抗可以抑制房性心律失常。

Methods

We conducted an investigator-initiated, phase 2, multicenter, randomized, double-blind, placebo-controlledtrial. Symptomatic adults with frequent PACs (≥1000/24 h) were randomly assigned to receive memantine or placebo for 6 weeks.

我们进行了一项由研究者发起的、II期、多中心、随机、双盲、安慰剂对照试验。有症状的成年人，其频繁的房性早搏（≥1000/24小时）被随机分配接受美金刚或安慰剂治疗，为期6周。

The primary end point was the percentage change in mean 24-hour PAC count from baseline to the end of treatment.

主要终点是基线至治疗结束时24小时平均醛固酮（PAC）计数的百分比变化。

The primary analysis was performed in the intention-to-treatpopulation.

主要分析是在意向治疗人群中进行的。

Prespecified secondary end points included the responder rate (≥50% PAC reduction), percentage change in nonsustained atrial tachycardia burden, and cumulative incidenceof new-onset atrial fibrillation.

预先设定的次要终点包括反应者率（≥50% PAC 减少）、非持续性房性心动过速负荷的百分比变化以及新发房颤的累积发生率。

Results

Among 241 patients included in the efficacy analysis, memantine resulted in a greater reduction in PAC count than placebo (between-group difference, 47.1 percentage points; P=0.0045).

在纳入疗效分析的241名患者中，与安慰剂相比，美金刚导致PAC计数的更大减少（组间差异，47.1个百分点；P=0.0045）。

The responder rate was higher with memantine than with placebo (52.4% versus 23.1%; P<0.0001).

与安慰剂相比，美金刚的反应者率更高（52.4%对23.1%；P<0.0001）。

Memantine also reduced nonsustained atrial tachycardia burden (between-group difference, 30.98 percentage points; P=0.0043) and was associated with a lower cumulative incidenceof new-onset atrial fibrillation (4.8% versus 23.9%; P<0.0001).

美金刚还减少了非持续性房性心动过速的负担（组间差异30.98个百分点；P=0.0043），并与其较低的新发房颤累积发生率相关（4.8%对23.9%；P<0.0001）。

No clinically meaningful differences were observed in electrocardiographic intervals or left ventricular function, and no drug-related serious adverse events occurred.

在心电图间期或左心室功能方面未观察到有临床意义的差异，且未发生与药物相关的严重不良事件。

Conclusions

In patients with frequent symptomatic PACs, memantine reduced atrial ectopy and atrial tachyarrhythmia burden and demonstrated a favorable safety profile.

在频繁出现症状性房性早搏（PACs）的患者中，美金刚减少了房性期外收缩和房性心动过速的负担，并显示出良好的安全性。

These findings provide proof of concept for a novel, non-ion channel-based therapeutic strategy targeting the cardiac glutamatergic system.

这些发现为一种新颖的非离子通道靶向心脏谷氨酸能系统的治疗策略提供了概念验证。

registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT06501638.

网址：https://www.clinicaltrials.gov；唯一标识符：NCT06501638。