ARB therapy is associated with a lower risk of subsequently developing epilepsy when compared to drugs from other anti-hypertensives classes
Angiotensin receptor blocker (ARB) therapy is associated with a reduced risk of epilepsy development over the next 5 years compared to other anti-hypertensive agents according to a cohort analysis by German researchers.
The epilepsies are one of the most common serious brain disorders and which can occur at any age with different presentations and causes. The World Health Organisation estimates that globally, around 5 million people are diagnosed with epilepsy each year and that across the world, roughly 50 million people are affected.
Interestingly, it has been suggested that based on both preclinical and clinical studies, that hypertension may be a cause of seizures and epilepsy through direct or indirect mechanisms and that the renin-angiotensin system might play a central role. Indeed, animal studies indicate that one class of antihypertensive medicines, ARB therapy and in particular, losartan, might be effective against seizure activity and neuronal damage in co-morbid hypertension and epilepsy.
Moreover, a study on cognition and prognosis in the Elderly with the ARB drug candesartan found that it may also have positive effects on cognitive function and quality of life. Taken to together, these findings would suggest that ARB therapy by protecting cognitive function may also reduce the risk of epilepsy development.
Since there are no data to support the theory that ARB therapy may affect the development of epilepsy, in the present study, the German researchers set out to compare the incidence of epilepsy after patients had been initiated on a range of different anti-hypertensive drug classes.
The team included adult patients with hypertension and an initial prescription for beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEi) and ARB therapy. These four anti-hypertensive classes were propensity matched 1:1:1:1 according to sex, age, index year and diagnosis. The researchers set the main outcome of interest as the incidence of epilepsy associated with ARB therapy compared to the other drug classes.
ARB therapy and epilepsy development
A total of 168,612 patients with a mean age of 62.3 years (48.6% male) were included with 42,153 individuals prescribed a drug from each of the different classes were followed-up for 5 years.
After 1 year, 0.27% of patients prescribed ARB therapy developed epilepsy and this increased to 0.99% after 5 years. In comparison, after 5 years, 1.47% of those prescribed beta-blockers and 1.48% of those given calcium channel blockers developed epilepsy.
ARB therapy was associated with a significantly reduced incidence of epilepsy (Hazard ratio, HR = 0.77, 95% CI 0.65 – 0.90, p < 0.002) compared with other anti-hypertensives drug classes. However, while this reduced risk in comparison to other drug classes was lower for all drugs within the ARB class examined, the association was only statistically significant for losartan.
The authors concluded that there was an association between a lower incidence of epilepsy in hypertensive patients prescribed ARB therapy compared to other anti-hypertensive drug classes. They called for additional research to better understand whether this relationship was causal and suggested that anti-hypertensives may represent a novel approach to the management of epilepsy in hypertensive patients.
Doege C et al. Association Between Angiotensin Receptor Blocker Therapy and Incidence of Epilepsy in Patients With Hypertension JAMA neurol 2022.