ARB therapy associated with a reduced risk of epilepsy

ARB therapy is associated with a reduced risk of later developing epilepsy compared to drugs from other antihypertensive classes

According to a cohort analysis by German researchers, therapy with angiotensin receptor blockers (ARBs) is associated with a reduced risk of developing epilepsy over the next 5 years compared to other antihypertensive agents.

Epilepsy is one of the most common serious brain diseases and can occur at any age with different characteristics and causes. The World Health Organization estimates that approximately 5 million people are diagnosed with epilepsy worldwide each year and that it affects approximately 50 million people worldwide. Interestingly, based on preclinical and clinical studies, it has been suggested that hypertension may be a cause of seizures and epilepsy through direct or indirect mechanisms and that the renin-angiotensin system may play a central role. In fact, animal studies suggest that a class of antihypertensive drugs, ARB therapy and specifically losartan, may be effective against seizures and neuronal damage in comorbid hypertension and epilepsy. Additionally, a study of cognition and prognosis in older people using the ARB drug candesartan found that it may also have positive effects on cognitive function and quality of life. Taken together, these results would suggest that by protecting cognitive function, ARB therapy may also reduce the risk of developing epilepsy.

Because there are no data to support the theory that ARB therapy might affect the development of epilepsy, in the present study the German researchers wanted to compare the onset of epilepsy after patients were started on a number of different classes of antihypertensive drugs. The team included adult patients with hypertension and a primary prescription for beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEi), and ARB therapy. These four antihypertensive classes were matched in a 1:1:1:1 ratio based on gender, age, index year, and diagnosis. The researchers identified the main outcome of interest, namely the incidence of epilepsy associated with ARB therapy compared to the other classes of drugs.

ARB therapy and epilepsy development

A total of 168,612 patients with a mean age of 62.3 years (48.6% male) were enrolled, with 42,153 subjects prescribed a drug from each of the different classes followed for 5 years.

At 1 year, 0.27% of patients prescribed ARB therapy developed epilepsy, and this number increased to 0.99% at 5 years. In comparison, at 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 to other antihypertensive drug classes. However, while this reduced risk was lower for all drugs within the ARB class studied compared to other drug classes, 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 antihypertensive drug classes. They called for additional research to better understand whether this association was causal and suggested that antihypertensive drugs could represent a new approach to treating epilepsy in hypertensive patients.

Citation
Doege C et al. Association between angiotensin receptor blocker therapy and epilepsy incidence in patients with hypertension JAMA neurol 2022