Association Between Sartan Therapy and Lower Incidence of Epilepsy in Hypertensive Patients?
Arterial hypertension (AH) is one of the non-cerebral comorbidities of epilepsy, with the renin-angiotensin system possibly being the central mediator of the connection between these diseases. The German study cited below therefore examined whether therapy with AT1 receptor blockers for angiotensin II (ARBs, i.e., sartans) reduces the risk of epilepsy in patients with AH as suggested by animal studies.
Study Methodology and Assessed Population
This retrospective cohort study included 168,612 adult patients (51.4% women; average age 62.3 years) from over 1.5 million hypertensives in the IQVIA database who were treated for AH by general practitioners between January 2010 and December 2020 and were first prescribed one of the 4 classes of antihypertensives as monotherapy: beta-blockers (BB), ARBs, angiotensin-converting enzyme inhibitors (ACEi), and calcium channel blockers (CCB). Each subgroup included 41,153 patients with a matching propensity score (according to age, gender, year of initiation of antihypertensive treatment, comorbidities, and head injuries) with comparable representation of dementias and cerebrovascular accidents (CVA) in medical history as risk factors for epilepsy. Patients with a diagnosis of epilepsy/antiepileptic drug use prior to or within 90 days of the initial antihypertensive prescription were excluded from the study.
The primary monitored parameter was the 5-year incidence of epilepsy. A total of 84,300 patients for whom this data was available were divided into subgroups according to the severity of hypertension during the 12 months before the monitored period (mild 140–159/90–99 mmHg, moderate 160–179/100–109 mmHg, and severe ≥ 180/≥ 110 mmHg). The authors assessed any association between the severity of hypertension and ARB prescription.
Findings
The lowest 5-year incidence of epilepsy was observed in the group of patients treated with sartans (0.27% at 1 year, 0.63% at 3 years, 0.99% at 5 years). This was a statistically significantly lower 5-year incidence of epilepsy compared to patients in the combined group with any other antihypertensive (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.65–0.90), compared to patients with BB (5-year incidence of epilepsy 1.47%) and with CCB (5-year incidence of epilepsy 1.48%).
When stratified by individual ARBs, a significant association with lower incidence of epilepsy was found only with losartan compared to BB, CCB, and the combined group of patients with any other class of antihypertensives.
CVA and dementia in the medical history were, as expected, associated with a higher risk of epilepsy (HR 1.93; 95% CI 1.65–2.67; p < 0.001, respectively HR 1.66; 95% CI 1.35–1.96; p < 0.001). Even in these patients, the association between sartan use and lower incidence of epilepsy was confirmed as in the entire study population, similarly noted in patients with a history of cerebrovascular disease, dementia, Parkinson's disease, or head trauma.
Regarding the severity of hypertension, no significant difference in the prescription of individual classes of antihypertensives was observed, except patients treated with BB more frequently had mild hypertension than patients with ARBs.
Conclusion
In the above-presented study, hypertension therapy with sartans was associated with a significantly lower risk of developing epilepsy compared to beta-blocker therapy, calcium channel blockers, and any other antihypertensive. These findings suggest that prescribing antihypertensives from the ARB group could represent a new approach to epilepsy prevention in hypertensive patients.
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Source: Doege C., Luedde M., Kostev K. Association between angiotensin receptor blocker therapy and incidence of epilepsy in patients with hypertension. JAMA Neurol 2022; 79 (12): 1296–1302, doi: 10.1001/jamaneurol.2022.3413.
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