A large analysis of electronic health records found that adults with epilepsy who started levetiracetam while already taking a direct oral anticoagulant (DOAC) had almost twice the risk of a serious blood clot, and about 60 percent higher mortality, compared with peers who started lamotrigine or lacosamide.
The finding, published online in JAMA Neurology by researchers at the University of Liverpool and the University of Zurich, is being described by the team as a safety signal rather than proof that the drug directly causes these outcomes.
Levetiracetam, sold under the brand name Keppra as well as Keppra XR, Elepsia XR, Spritam and various generics, is one of the most widely used antiseizure medications in the world.
It is often preferred for patients on blood thinners because it has generally been assumed to have few drug interactions.
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What the study actually measured
The researchers used the international TriNetX network to identify 9,529 adults with epilepsy who started an antiseizure medication while already on a DOAC, drawing from a pool of more than 2.29 million adults with epilepsy across 165 healthcare organizations.
Roughly 57 percent of the cohort initiated levetiracetam. The average age was 63, and just over half of participants were women.
Compared with an active reference of lamotrigine or lacosamide, the study reported a hazard ratio of 1.98 for the primary thromboembolic outcome, which combined ischemic stroke, heart attack, and pulmonary or systemic embolism.
All-cause mortality carried a hazard ratio of 1.60. Major bleeding rates did not differ significantly between the groups.
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DOACs are a class of blood thinners that includes apixaban and rivaroxaban.
They are widely prescribed for atrial fibrillation, an irregular heart rhythm that raises stroke risk.
The UK research team estimates that around 36,000 of the 600,000 people living with epilepsy in the United Kingdom are on both a DOAC and an antiseizure medication at the same time, or roughly 6 percent of the epilepsy population.
What patients should do next
The single most important message from the researchers is that no one should change their own regimen based on this study.
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Patients should not stop or change their antiseizure medication or anticoagulant without medical advice, Mbizvo said.
Stopping a seizure medication abruptly can trigger seizures, and stopping a DOAC can raise the risk of the very strokes it is meant to prevent.
For readers already taking both Keppra and a DOAC, the practical step is to bring up the study at the next scheduled appointment with the neurologist or cardiologist managing the prescriptions.
The UK Medicines and Healthcare products Regulatory Agency has been notified of the findings and is expected to review the signal.
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This article is made and published by Ida-Marie Palm Varbæk, who may have used AI in the preparation.