拉莫三嗪与心房颤动的关联：一项观察性队列研究。

Association of atrial fibrillation with lamotrigine: An observational cohort study.

作者信息

Kim Sodam, Welch Landon, Santos Bertha De Los, Radwański Przemysław B, Munger Mark A, Kim Kibum

机构信息

Department of Pharmacy Systems and Outcomes and Policy, University of Illinois at Chicago, Chicago, Illinois, USA.

Department of Pharmacotherapy, University of Utah Health, Salt Lake City, Utah, USA.

出版信息

Pharmacotherapy. 2025 Jan;45(1):20-32. doi: 10.1002/phar.4633. Epub 2024 Dec 13.

DOI:10.1002/phar.4633

PMID:39673065

Abstract

BACKGROUND

Drug-induced atrial fibrillation (AF) is recognized as an important causal association. Lamotrigine (LTG) is a widely prescribed neurological agent with Class IB antiarrhythmic properties at therapeutically relevant concentrations. The United States Food and Drug Administration has issued a warning for a higher risk of LTG proarrhythmic events in patients with structural heart disease (SHD) and/or myocardial ischemia. This study evaluated the incidence of AF with LTG use.

METHODS

A retrospective observational study was performed using a large healthcare claims database of adult participants analyzing 2 years AF incidence. The analytic cohort included adult participants with bipolar I disorder (BPD), partial seizures (PSZ), or generalized tonic-clonic seizures (GTSZ). Exposure to LTG was compared with commonly prescribed alternative agents as the control comparators (CTR). Participants were free from supraventricular or ventricular arrhythmias during the 6 months baseline period prior to the index LTG or CTR date. Kaplan-Meier estimator calculated 2 years cumulative AF incidence, with participants censored at last enrollment, treatment switching, or discontinuation. The AF association hazard ratios (HR) for LTG versus CTR were adjusted for baseline characteristics.

RESULTS

The analytic cohort with BPD, PSZ, and GTSZ consisted, respectively, of 150,470 LTG versus 204,704 CTR, 9565 LTG versus 21,595 CTR, and 5505 LTG versus 15,513 CTR patients. In a predominantly middle-aged female population at baseline, the prevalence of cardiovascular conditions was low. The 12 months cumulative incidence of AF for LTG versus CTR was 0.764% versus 0.642% among BPD, 0.833% versus 0.646% among PSZ, and 0.585% versus 0.338% among GTSZ, respectively. The adjusted 365-day HR [95% confidence interval CI] of AF for LTG versus CTR in the BPD, PSZ, and CTSZ groups was 1.257 [1.088-1.453], 1.651 [1.104-2.468], and 1.451 [0.770-2.734], respectively.

CONCLUSIONS

In adult AF-naïve participants, LTG has a strong association with increased AF risk compared with commonly prescribed alternatives.

摘要

背景

药物性心房颤动（AF）被认为是一种重要的因果关联。拉莫三嗪（LTG）是一种广泛使用的神经药物，在治疗相关浓度下具有IB类抗心律失常特性。美国食品药品监督管理局已发出警告，结构性心脏病（SHD）和/或心肌缺血患者发生LTG促心律失常事件的风险更高。本研究评估了使用LTG时AF的发生率。

方法

使用一个大型医疗保健索赔数据库对成年参与者进行回顾性观察研究，分析2年的AF发病率。分析队列包括患有双相I型障碍（BPD）、部分性癫痫（PSZ）或全身强直阵挛性癫痫（GTSZ）的成年参与者。将LTG暴露与常用的替代药物作为对照比较（CTR）。在索引LTG或CTR日期之前的6个月基线期内，参与者无室上性或室性心律失常。采用Kaplan-Meier估计器计算2年累积AF发病率，参与者在最后一次入组、治疗转换或停药时进行截尾。对LTG与CTR的AF关联风险比（HR）进行基线特征调整。

结果

BPD、PSZ和GTSZ的分析队列分别包括150470例LTG患者与204704例CTR患者、9565例LTG患者与21595例CTR患者以及5505例LTG患者与15513例CTR患者。在基线时以中年女性为主的人群中，心血管疾病的患病率较低。在BPD患者中，LTG与CTR的AF 12个月累积发病率分别为0.764%和0.642%；在PSZ患者中分别为0.833%和0.646%；在GTSZ患者中分别为0.585%和0.338%。BPD、PSZ和CTSZ组中，LTG与CTR的AF调整后365天HR[95%置信区间CI]分别为1.257[1.088-1.453]、1.651[1.104-2.468]和1.451[0.770-2.734]。