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癫痫患者和抗癫痫药物使用者的院外心脏骤停风险。

Risk of out-of-hospital cardiac arrest in patients with epilepsy and users of antiepileptic drugs.

机构信息

Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.

Department of Experimental and Clinical Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

Br J Clin Pharmacol. 2022 Aug;88(8):3709-3715. doi: 10.1111/bcp.15313. Epub 2022 Mar 26.

Abstract

AIMS

A few studies suggested that epilepsy and antiepileptic drugs with sodium channel-blocking properties were independently associated with out-of-hospital cardiac arrest (OHCA). However, these findings have not yet been replicated.

METHODS

Using Danish registries, we conducted a nested case-control study in a cohort of individuals between 1 June 2001 and 31 December 2015. Cases were defined as OHCA from presumed cardiac causes, and were matched with non-OHCA-controls based on sex, and age on the date of OHCA. Exposure of interest was epilepsy or antiepileptic drug use. To study the association between individual antiepileptic drug use and the rate of OHCA, we compared each antiepileptic drug with valproic acid. Cox regression with time-dependent covariates was conducted to calculate hazard ratio (HR) and 95% confidence interval (CI).

RESULTS

We identified 35 195 OHCA-cases and 351 950 matched non-OHCA controls. Epilepsy (cases: 3.58%, controls: 1.60%) was associated with increased rate of OHCA compared with the general population (HR: 1.76, 95%CI: 1.64-1.88) when common OHCA risk factors were taken into account. When we studied antiepileptic drug use, we found that 2 antiepileptic drugs without sodium channel blockage, clonazepam (HR: 1.88, 95%CI: 1.45-2.44) and pregabalin (HR: 1.33, 95%CI: 1.05-1.69), were associated with OHCA, whereas none of the antiepileptic drugs with sodium channel blockage were associated with OHCA.

CONCLUSION

Epilepsy is associated with increased rate of OHCA. Our findings do not support a possible association between antiepileptic drugs with sodium channel-blocking properties and OHCA.

摘要

目的

有几项研究表明,癫痫和具有钠通道阻断特性的抗癫痫药物与院外心脏骤停(OHCA)独立相关。然而,这些发现尚未得到复制。

方法

我们使用丹麦登记处,在 2001 年 6 月 1 日至 2015 年 12 月 31 日期间的队列中进行了一项嵌套病例对照研究。病例定义为推定心源性 OHCA,并根据性别和 OHCA 发生日期与非 OHCA 对照相匹配。感兴趣的暴露是癫痫或抗癫痫药物的使用。为了研究个体抗癫痫药物使用与 OHCA 发生率之间的关系,我们将每种抗癫痫药物与丙戊酸进行了比较。使用时间依赖性协变量的 Cox 回归计算了危险比(HR)和 95%置信区间(CI)。

结果

我们确定了 35195 例 OHCA 病例和 351950 例匹配的非 OHCA 对照。考虑到常见的 OHCA 危险因素,与普通人群相比,癫痫(病例:3.58%,对照:1.60%)与 OHCA 发生率增加相关(HR:1.76,95%CI:1.64-1.88)。当我们研究抗癫痫药物的使用时,我们发现 2 种没有钠通道阻断作用的抗癫痫药物,氯硝西泮(HR:1.88,95%CI:1.45-2.44)和普瑞巴林(HR:1.33,95%CI:1.05-1.69)与 OHCA 相关,而没有一种具有钠通道阻断作用的抗癫痫药物与 OHCA 相关。

结论

癫痫与 OHCA 发生率增加有关。我们的研究结果不支持具有钠通道阻断特性的抗癫痫药物与 OHCA 之间可能存在关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad05/9542728/b5d69e42ee42/BCP-88-3709-g002.jpg

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