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

Katharina Platzbecker, Helge Müller-Fielitz, Ronja Foraita, Matthias J Koepp, Annemarie Voss, René Pflock, Roland Linder, Iris Pigeot, Tania Schink, Markus Schwaninger

Journal: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2023;25(5):euad087

PMID: 37013704

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.

© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.

Address: Leibniz Institute for Prevention Research and Epidemiology-BIPS, Achterstraße 30, 28359 Bremen, Germany.; Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany.; Department of Clinical and Experimental Epilepsy, University College London Queen Square Institute of Neurology, Queen Square, Box 29, London WC1N 3BG, United Kingdom.; Techniker Krankenkasse, Bramfelder Straße 140, 22305 Hamburg, Germany.; Faculty of Mathematics and Computer Science, University of Bremen, Bibliothekstraße 5, 28334 Bremen, Germany.; DZHK (German Research Centre for Cardiovascular Research), Hamburg-Lübeck-Kiel, Germany.
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