Varenicline and Ventricular Ectopy After Myocardial Infarction: A Randomized Phase 2 Study.

Cardiac nicotinic acetylcholine receptors (nAChRs) represent a novel electrophysiological target.

心脏烟碱型乙酰胆碱受体（nAChRs）代表了一种新的电生理靶点。

The aim of this exploratory, proof-of-concept phase 2 trial was to evaluate the effect of varenicline, a partial nAChR agonist, on frequent premature ventricular complexes (PVCs) after myocardial infarction (MI) and to assess its short-term safety and biological target engagement.

本项探索性、概念验证的二期试验旨在评估部分尼古丁型乙酰胆碱受体激动剂伐尼克兰对心肌梗死后频繁出现的室性早搏（PVCs）的影响，并评估其短期安全性和生物学靶点的参与度。

Methods

In this multicenter, randomized, double-blind, placebo-controlledtrial, adults with frequent PVCs (≥1,000/24 h) assessed using 72-hour ambulatory electrocardiographic monitoring at ≥4 weeks post-MI were randomly assigned (1:1) to varenicline 0.5 mg twice daily or matching placebo for 45 days, in addition to guideline-directed medical therapy.

在这项多中心、随机、双盲、安慰剂对照试验中，心肌梗死后≥4周，使用72小时动态心电图监测评估频繁PVCs（≥1,000/24小时）的成年患者被随机分配（1:1）接受伐尼克兰0.5毫克每日两次或匹配安慰剂治疗45天，此外还接受指南推荐的药物治疗。

The primary endpoint was the percentage change in 24-hour PVC count from baseline to week 6.

主要终点是24小时室性早搏(PVC)计数从基线到第6周的百分比变化。

Key secondary endpoints included responder rate (≥50% reduction in PVC count) and the incidenceof nonsustained ventricular tachycardia (VT).

关键次要终点包括反应者率（PVC计数减少≥50%）和非持续性室性心动过速(VT)的发生率。

Results

Among 118 randomized patients, varenicline produced a 60.1 percentage point greater reduction in PVC burden compared with placebo (95% CI: 21.3-98.8 percentage points; P = 0.001).

在118名随机患者中，与安慰剂相比，伐尼克兰使室性早搏（PVC）负荷减少了60.1个百分点（95%置信区间：21.3-98.8个百分点；P = 0.001）。

The responder rate was higher with varenicline (67.8% vs 30.5%; RR: 2.22; 95% CI: 1.46-3.39; P < 0.0001), and nonsustained VT incidencewas lower (20.3% vs 37.3%; RR: 0.49; 95% CI: 0.29-0.85; P = 0.007).

伐尼克兰的应答率更高（67.8%对比30.5%；相对风险RR: 2.22；95%置信区间：1.46-3.39；P < 0.0001），非持续性室性心动过速（VT）的发生率更低（20.3%对比37.3%；相对风险RR: 0.49；95%置信区间：0.29-0.85；P = 0.007）。

No deaths or malignant ventricular arrhythmias occurred in the varenicline group, with comparable adverse eventrates between groups.

在伐尼克兰组中，没有发生死亡或恶性室性心律失常，两组的不良事件发生率相当。

Conclusions

In this phase 2 trial, varenicline significantly reduced PVC burden and nonsustained VT incidencein post-MI patients without evidence of a proarrhythmic effects.

在这项2期试验中，伐尼克兰显著减少了心肌梗死（MI）后患者的室性早搏（PVC）负担和非持续性室性心动过速（VT）的发生率，且未显示出促心律失常效应。

These findings support cardiac nAChRs as a potential antiarrhythmic target and justify further evaluation in larger outcome-driven trials.

这些发现支持心脏尼古丁型乙酰胆碱受体（nAChRs）作为潜在的抗心律失常靶点，并证明了在更大规模的结果驱动试验中进一步评估的合理性。

(Efficacy of Varenicline Tartrate in Treating Frequent Premature Ventricular Contractions: A Multicenter, Randomized, Double-Blind, Placebo-ControlledTrial [Var-PVC]; NCT06780215).

(酒石酸伐尼克兰治疗频繁室性早搏的有效性：一项多中心、随机、双盲、安慰剂对照试验 [Var-PVC]; NCT06780215).