Angiotensin Receptor Blockers Associated With Lower Epilepsy Risk in Hypertension

An observational study that analyzed medical records of 2.26 million patients with hypertension found a roughly 30% decrease in risk for new-onset epilepsy for patients receiving angiotensin receptor blockers (ARBs) compared with other antihypertensive agents.

The retrospective cohort study, published in JAMA Neurology,¹ used propensity score matching to evaluate 619,858 patients for ARBs vs angiotensin-converting enzyme (ACE) inhibitors; 619,828 patients for ARBs vs β-blockers; and 601,002 patients for ARBs vs calcium channel blockers (CCBs).

Patients who took an ARB exhibited a significantly lower incidence of epilepsy compared with ACE inhibitors (adjusted HR [aHR], 0.75; 95% CI, 0.58-0.96), β-blockers (aHR, 0.70; 95% CI, 0.54-.090), or other hypertensive medication classes (aHR, 0.72; 95% CI, 0.56-0.95). No significant association with the incidence of epilepsy was found when comparing ARBs and CCBs (aHR, 0.80; 95% CI, 0.61-1.04).

Kimford J. Meador, MD, FAAN, FAES, FRCPE, Stanford Neuroscience Health Center | Image Credit: Stanford University

“Angiotensin was originally developed for blood pressure treatment because it is very effective in regulating blood pressure. But now we see that this drug has a whole different role in the body, of regulating inflammation,” said study coauthor Kimford J. Meador, MD, FAAN, FAES, FRCPE, professor in the Department of Neurology & Neurological Sciences at Stanford University School of Medicine’s Stanford Neuroscience Health Center.

“I think that the underlying mechanisms may be that it is affecting inflammation, which may apply not just to risk of epilepsy in people with hypertension, but might apply to people with head trauma or some other risk factor for epilepsy,” he added.

The findings corroborated a previous study from Germany, as well as animal studies that had discovered that losartan consistently lowered epilepsy risk compared with other individual or combined antihypertensive medications. No statistically significant association was found when comparing high and low doses of losartan, but that finding could change with a larger sample size for the 2 dose subgroups, the authors concluded.

The findings were consistent across subgroups, except for sex when comparing ARBs with ACE inhibitors. Female patients using ARBs exhibited a 34% lower incidence of epilepsy (aHR, 0.66; 95% CI, 0.47-0.94), while male ARB users had no significant change in epilepsy risk (aHR, 0.87; 95% CI, 0.60-1.28) compared with the ACE inhibitor patient group.

The study analyzed data from a national health administrative database for January 2010 to December 2017. All patients were privately insured adults diagnosed with primary hypertension, with no preexisting stroke or cardiovascular disease. Researchers selected only patients who had been dispensed at least 1 ARB, ACE inhibitor, β-blocker, or CCB between January 2010 and December 2017. Patients were excluded from the study if they had a diagnosis of epilepsy at or before the start of the study, which was conducted from April 2022 to April 2024, or if they were dispensed an antiseizure medication 12 months before or 90 days after starting the study medications. Patients who developed stroke during the study or follow-up period were also excluded. Each patient was monitored until one of the following occurred: the first diagnosis of epilepsy or stroke, a switch of study medications, loss of insurance eligibility, or the end of the study period.

In 2017, 81.7 million American adults had a diagnosis of primary hypertension and 76% reported using antihypertensive medications, according to the study. Nearly 3 million American adults had epilepsy in 2021, and health care costs related to epilepsy ran into the billions, according to the CDC.²

“This is very exciting, because we don't have drugs that are truly antiepileptics. Here's a drug on the open market that looks like it can protect against epilepsy. The reduction is about 30%,” said Meador. “We just need a randomized clinical trial to see if it’s really true. If it is, I think it will really alter practice.”

References

1. Wen X, Otoo M, Tang J, et al. Angiotensin receptor blockers for hypertension and risk of epilepsy. JAMA Neurol. 2024:e241714. doi:10.1001/jamaneurol.2024.1714.

2. Epilepsy facts and stats. CDC. Accessed June 24, 2024. https://www.cdc.gov/epilepsy/data-research/facts-stats/index.html#:~:text=Key%20points,12%20months%20(or%20both)