Association Between Angiotensin Receptor Blocker Therapy and Incidence of Epilepsy in Patients With Hypertension

Abstract

ImportanceArterial hypertension is associated with an increased incidence of epilepsy. Results from animal studies suggest that angiotensin receptor blocker (ARB) therapy could inhibit epileptic seizures. However, there is a lack of clinical data to support the use of ARB therapy in humans.ObjectiveTo assess whether ARB therapy is associated with a decreased incidence of epilepsy in patients with hypertension.Design, Setting, and ParticipantsThis cohort study obtained data from the Disease Analyzer database (IQVIA) on patients aged 18 years or older who had hypertension and at least 1 antihypertensive drug prescription. Patients were treated at 1274 general practices between January 2010 and December 2020 in Germany. Data were available for 1 553 875 patients who had been prescribed at least 1 antihypertensive drug. Patients diagnosed with epilepsy before or up to 3 months after the index date were excluded. A total of 168 612 patients were included in propensity score matching. Patients treated with 1 of 4 antihypertensive drug classes (β-blockers, ARBs, angiotensin-converting enzyme inhibitors, and calcium channel blockers [CCBs]) were matched to each other using propensity scores.Main Outcomes and MeasuresThe main outcome of the study was the incidence of epilepsy associated with ARB therapy compared with other antihypertensive drug classes. Cox regression models were used to study the association between the incidence of epilepsy and ARBs compared with all other antihypertensive drug classes as a group.ResultsThe study included a total of 168 612 patients, with 42 153 in each antihypertensive drug class. The mean [SD] age of patients was 62.3 [13.5] years, and 21 667 (51.4%) were women. The incidence of epilepsy within 5 years was lowest among patients treated with ARBs (0.27% at 1 year, 0.63% at 3 years, 0.99% at 5 years) and highest among patients receiving β-blockers and CCBs (0.38% for both β-blockers and CCBs at 1 year; 0.91% for β-blockers and 0.93% for CCBs at 3 years; β-blockers, 1.47%; and CCBs, 1.48% at 5 years). Angiotensin receptor blocker therapy was associated with a significantly decreased incidence of epilepsy (hazard ratio, 0.77; 95% CI, 0.65-0.90) compared with the other drug classes as a group.Conclusions and RelevanceIn this cohort study of patients with hypertension, ARB therapy was associated with a significantly decreased incidence of epilepsy. The findings suggest antihypertensive drugs could be used as a novel approach for preventing epilepsy in patients with arterial hypertension.

Knockdown ofNeuroD2leads to seizure-like behaviour, brain neuronal hyperactivity and a leaky blood-brain barrier in aXenopus laevistadpole model of DEE75

“…A recent retrospecJve study showed significantly reduced epilepsy incidence in a cohort of arterial hypertension paJents from Germany who were being treated with six different angiotensin II receptor blockers (Losartan, Valsartan, Telmisartan, Olmesartan, Candesartan, Irbesartan). The same study showed that Losartan alone associated with a significantly lower incidence of epilepsy (DOEGE et al 2022). Losartan was also effecJve at reducing seizures and associated neuronal damage in a mouse model of hypertension and epilepsy (TCHEKALAROVA et al 2016).…”

Anti-Epileptogenesis: Some Roads Lead to Losartan

“…In this study, 5 the authors tried to answer the questions by analyzing a large German insurance claims database covering 3% of all outpatient practices in Germany. The study was based on ICD-10 codes, and included adults with an International Classification of Diseases (ICD-10) code for hypertension and prescription of an antihypertensive agent; beta-blockers (BB), calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEi), and angiotensin receptor blockers (ARB).…”

Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy

“…Losartan, an ARB medication, has been shown to block astrocyte activation and maintain the integrity of the blood brain barrier (BBB) in animal and human studies . A retrospective analysis of a health administrative database in Germany found a lower incidence of epilepsy in ARB users compared with other classes of antihypertensive medications . However, the study results have not been extrapolated to the US population.…”