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. 2023 May 19;25(5):euad087.
doi: 10.1093/europace/euad087.

In atrial fibrillation epilepsy risk differs between oral anticoagulants: active comparator, nested case-control study

Katharina Platzbecker  1 , Helge Müller-Fielitz  2 , Ronja Foraita  1 , Matthias J Koepp  3 , Annemarie Voss  1 , René Pflock  2 , Roland Linder  4 , Iris Pigeot  1   5 , Tania Schink  1 , Markus Schwaninger  2   6
Affiliations

In atrial fibrillation epilepsy risk differs between oral anticoagulants: active comparator, nested case-control study

Katharina Platzbecker et al. Europace. .

Abstract

Aims: Atrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC).

Methods and results: We performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004. In 2011-17, 227 707 AF patients initiated treatment with a DOAC or PPC, of which 1828 cases developed epilepsy on current treatment with an oral anticoagulant. They were matched to 19 084 controls without epilepsy. Patients with DOAC treatment for AF had an overall higher risk of epilepsy with an odds ratio of 1.39, 95% CI (1.24; 1.55) compared to current PPC treatment. Cases had higher baseline CHA2DS2-VASc scores and more frequently a history of stroke than controls. After excluding patients with ischaemic stroke prior to the diagnosis of epilepsy, the risk of epilepsy was still higher on DOACs than on PPC. In contrast, within a cohort of patients with venous thromboembolism, the risk of epilepsy on treatment with DOACs was less elevated [adjusted odds ratio 1.15, 95% CI (0.98; 1.34)].

Conclusion: In patients with AF initiating oral anticoagulation, treatment with a DOAC was associated with an increased risk of epilepsy compared to the vitamin K antagonist PPC. Covert brain infarction may explain the observed elevated risk of epilepsy.

Keywords: Anticoagulation; Atrial fibrillation; Direct oral anticoagulants; Epilepsy; Silent stroke; Vitamin K antagonist.

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Conflict of interest statement

Conflict of interest: The funder of the study, Federal Joint Committee in Germany, had no influence on the design and conduct of the study, the interpretation of the data, or the decision to publish. K.P., R.F., A.V., I.P., and T.S. are working at an independent, non-profit research institute, the Leibniz Institute for Prevention Research and Epidemiology—BIPS. Unrelated to this study, BIPS occasionally conducts studies financed by the pharmaceutical industry. Almost exclusively, these are post-authorization safety studies requested by health authorities. The design and conduct of these studies as well as the interpretation and publication are not influenced by the pharmaceutical industry. No financial relationships with any organizations that might have an interest in the submitted work in the previous three years; No other relationships or activities that could appear to have influenced the submitted work.

Figures

Graphical Abstract
Graphical Abstract
Created by BioRender.com.
Figure 1
Figure 1
Flowchart of the study cohort according to the defined inclusion and exclusion criteria. The diagnosis of epilepsy at any time before cohort entry (exclusion criteria) was based on the International Classification of Diseases, 10th revision, German modification (ICD-10-GM) codes listed in Supplementary material online, Table S7.
Figure 2
Figure 2
Forest plot of the estimated risk of epilepsy or seizures comparing current use of a direct oral anticoagulant with current use of phenprocoumon in patients with atrial fibrillation (A) and in patients with venous thromboembolism (B), respectively. Results are presented as matched adjusted odds ratios with corresponding 95% confidence intervals. AF, atrial fibrillation; DOAC, direct oral anticoagulant; PPC, phenprocoumon; VTE, venous thromboembolism.
See this image and copyright information in PMC

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