ARBs Cut Epilepsy Risk in Patients with Hypertension

LOS ANGELES — Angiotensin receptor blockers (ARB) are more effective than other antihypertensive medications in reducing the risk for post-stroke epilepsy (PSE), new research showed.

Investigators found ARBs are better at cutting the PSE risk in individuals with high blood pressure than angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), and beta-blockers (BBs).

The results suggested ARBs could be a frontline strategy to proactively forestall development of epilepsy in patients with a history of stroke and hypertension, said the study’s co-lead investigator Giacomo Evangelista, MD, PhD, a resident in neurology at the Epilepsy Center at “G. d’Annunzio” University of Chieti-Pescara, Italy.

The findings were presented on December 9, 2024, at American Epilepsy Society (AES) 78th Annual Meeting 2024.

Stroke and Seizures Tightly Linked

Stroke is the most common cause of seizures in patients older than 60 years. About 6%-8% of new epilepsy diagnoses in older adult patients are associated with a brain ischemic event.

Hypertension is among the most common risk factors for both epilepsy and stroke. The European Society of Cardiology recommends ACE inhibitors and ARBs be considered first-line hypertension treatments.

ARBs seem to provide a protective effect in terms of seizures in the general population, but their possible preventive role in PSE has not been clear.

The retrospective, observational study included 528 patients (mean age, 71.4 years; 57.19% men) with hypertension and ischemic stroke without a history of epilepsy.

Researchers divided patients into those who developed PSE during the 2-year follow-up and those who didn’t. The main outcome was incidence of PSE associated with ARB therapy compared with other antihypertensive drug classes (ACE inhibitors, CCBs, and BBs).

Of the total, 7.2% of patients developed PSE. The study found patients treated with an ARB had a lower risk for PSE (P = .009). PSE incidence was higher among patients receiving CCBs (P = .019) and BBs (P = .008), but ACE inhibitors did not appear to affect PSE risk.

Further analysis showed patients taking a BB were 120% more likely to develop PSE, and those taking a CCB were 110% more likely to develop PSE than those taking an ARB. The corresponding comparison was 65% for those taking an ACE inhibitor.

Potential Mechanisms

ARBs block the angiotensin II type 1 receptor, which may lead to numerous neuroprotective benefits such as improved blood flow to the brain and less neuroinflammation. The blockage may also reduce epilepsy severity and seizure frequency.

ACE inhibitors work in the same system as ARBs but don’t bind directly to the angiotensin receptor. Experts believe these drugs may lead to inflammation that raises the risk for PSE.

CCBs and BBs may increase the likelihood of seizures by inducing excessive excitability in the brain, which can trigger seizures.

Other research presented at the meeting found ARBs reduce the risk for epilepsy in patients with hypertension even in the absence of stroke.

Using data from an US national administrative database, the retrospective cohort study included 2,261,964 eligible adult beneficiaries diagnosed with hypertension and dispensed at least one ARB, ACE inhibitor, BB, or CCB from 2010 to 2017.

The study found ARBs were associated with lower epilepsy incidence than ACE inhibitors (hazard ratio [HR], 0.75; 95% CI, 0.58-0.96), BBs (HR, 0.70; 95% CI, 0.54-0.90), and CCBs (HR, 0.80; 95% CI, 0.61-1.04).

The effect was most robust for the ARB losartan and among patients with no preexisting stroke or cardiovascular conditions.

Researchers ran the analysis excluding stroke and the association was still there, lead study author Kimford Meador, MD, professor of neurology and neurological sciences, Stanford University, Palo Alto, California, told Medscape Medical News. “People with hypertension who use ARBs — even if they don’t have a stroke — are less likely to develop epilepsy than if they use other major anti-hypertensives.”

Exciting and Suggestive

These new studies are “exciting” and “very suggestive,” said Meador. “We don’t have any true antiepileptic drugs; we have antiseizure medications. If we could reduce the incidence of epilepsy, that would be a very big thing.”

But the research to date hasn’t been “definitive” and is subject to bias, he said. “What we really need is a large randomized controlled trial to see if this is real because any observational study in humans has the potential for confounding from unmeasured variables.”

If such a study does show the effect is real, “that would change clinical practice,” said Meador.

As ARBs have anti-inflammatory effects, researchers are now investigating whether this class of drugs might be useful in other diseases linked to inflammation such as multiple sclerosis, said Meador.

Speaking to Medscape Medical News, Alain Zingraff Looti, MD, assistant professor of neurology and public health sciences, Penn State College of Medicine, Hershey, Pennsylvania, said this new research is “important” although still at a “very preliminary stage.”

As the studies so far have all been observational, “they showed an association, but that doesn’t mean causality,” said Looti. These studies just looked at known potential confounders, “and there may be some unknown confounders that could explain the association,” he added.

But he acknowledged the results make sense from a biological standpoint. He noted that infusing ARBs into rats causes a “cascade reaction” leading to reduced inflammation in the brain and then to less epilepsy. “Inflammation plays a major role in several models of epilepsy,” he added.

While these new results are important, Looti, too, would like to see a randomized controlled trial to confirm the findings.

Looti and Meador reported no relevant financial disclosures.