This cohort study assesses whether the use of angiotensin receptor blocker therapy is associated with a reduced incidence of epilepsy in patients with hypertension.
Key Points
Question
Are angiotensin receptor blockers associated with a reduced incidence of epilepsy in patients with arterial hypertension?
Findings
In this cohort study of 168 612 outpatients with arterial hypertension, the use of angiotensin receptor blockers was associated with a significantly decreased incidence of epilepsy compared with other classes of antihypertensive drugs.
Meaning
The findings of this study suggest that use of angiotensin receptor blockers in patients with hypertension may be a novel approach for prevention of epilepsy in this population.
Abstract
Importance
Arterial 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.
Objective
To assess whether ARB therapy is associated with a decreased incidence of epilepsy in patients with hypertension.
Design, Setting, and Participants
This 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 Measures
The 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.
Results
The 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 Relevance
In 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.
Introduction
Epilepsy is a chronic neurological disease with a high prevalence that is heterogeneous with regard to seizure types, cause, and disease course.1 It is characterized by recurrent seizures owing to synchronous abnormal or excessive neural activity in the brain.2 The condition affects more than 50 000 000 people worldwide.3 There are various well-established antiseizure medications that can reliably prevent the recurrence of seizures in many patients. However, epilepsy is refractory to the established therapies in some patients,4 and particularly in those with a refractory course of the disease, there is a risk of social and mental complications, such as depression and impaired cognitive abilities.4
The establishment of numerous innovative antiseizure medications with widely varying mechanisms of action has greatly expanded the spectrum of therapeutic approaches.5 Whether the availability of these medications has improved the overall outcomes of patients with epilepsy remains controversial.6 The need for new therapeutic approaches to treat and prevent epilepsy therefore remains. In this context, the association of epilepsy with cerebral and noncerebral comorbidities recognized in recent years could be a starting point. Arterial hypertension is 1 noncerebral comorbidity associated with the occurrence of epilepsy,7 with the renin-angiotensin-aldosterone system appearing to act as a central mediating signaling pathway.7 Antihypertensive drugs that inhibit the renin-angiotensin-aldosterone system may also have a pleiotropic antiepileptic treatment effect. Initial studies suggest that angiotensin II receptor blockers (ARBs) have a possible antiepileptic treatment effect.8,9 In animal studies, losartan displays an antiepileptogenic effect by inhibiting the albumin-induced transforming growth factor β (TGFB) signaling cascade, which has been implicated in enhancing neuronal excitability and excitatory synaptogenesis after blood-brain barrier damage and inflammation.10 Retrospective clinical studies support the assumption that ARBs offer relative neuroprotection compared with other antihypertensive drugs.11,12
The aim of the present study was to assess whether an association exists between use of ARB therapy and the incidence of epilepsy and to compare the incidence of the disease associated with different groups of antihypertensive drugs in a large sample of patients with hypertension.
Methods
Database
This retrospective cohort study was based on data from the Disease Analyzer database (IQVIA), which was obtained directly and anonymously from computer systems used in general practitioner and specialist practices.13 The database covers approximately 3% of all outpatient practices in Germany. IQVIA monitors diagnoses (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes), prescriptions (according to the Anatomical Therapeutic Chemical [ATC] classification system), basic medical and demographic characteristics, and the quality of reported data. The panel of practices included in the Disease Analyzer database is representative of general and specialized practices in Germany.13 In addition, this database has already been used in previous studies focusing on epilepsy.14,15,16,17 This study was approved by the local ethics committee of Christian-Albrechts-University (CAU) Kiel, Germany, with a waiver of the informed consent requirement because we used only anonymized data. This study was performed in accordance with the Declaration of Helsinki, the Good Practice of Secondary Data Analysis guidelines,18 and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Study Population
The study included adult patients (aged ≥18 years) with an arterial hypertension (ICD-10 code I10) and an initial prescription of plain antihypertensive medication (β-blockers, ATC code C07A; calcium channel blockers [CCBs], ATC code C08A; angiotensin-converting enzyme [ACE] inhibitors, ATC code C09A; ARBs, ATC code C09A) who were treated at 1274 general practices in Germany between January 2010 and December 2020 (index date; Figure 1). Diuretic agents were not included because these were prescribed mainly to treat other diseases (heart failure, coronary heart disease, and kidney failure). Patients with an epilepsy or status epilepticus diagnosis (ICD-10 codes G40, G41) or antiseizure medication prescriptions (ATC code N03) before, on, or within 90 days after the index date were excluded from the analysis.
Figure 1. Flowchart of Study Population.
ACE indicates angiotensin-converting enzyme; CCBs, calcium channel blocker; ARBs, angiotensin receptor blockers; ICD-10, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10).
Four antihypertensive drug classes were matched to each other 1:1:1:1 by propensity scores according to sex, age, index year, and diagnoses documented within 12 months before or on the index date, including diabetes (ICD-10 codes E10 and E11), cerebrovascular diseases (ICD-10 codes I60-I69 and G45), Parkinson disease (ICD-10 codes G20 and G21), dementia and mild cognitive impairment (ICD-10 codes F00-F03, F06.7, and G30), and head injuries (ICD-10 codes S00-S09). These disorders have been found to be associated with late-onset epilepsy.17
Study Outcomes, Covariates, and Post Hoc Analysis
The main outcome of the study was the incidence of epilepsy (ICD-10 code G40) associated with ARB therapy compared with other antihypertensive drug classes. Each patient was followed up from day 91 after the index date for a period of up to 5 years until the first epilepsy diagnosis was documented or plain antihypertensive therapy ended (either switched to another plain antihypertensive therapy or added another drug class to the initial therapy).
We also assessed the mean blood pressure value per patient within 12 months before or on the index date to investigate whether there was an association between hypertension severity and ARB prescription. These values were available for 84 300 patients. Patients were also classified into 3 groups in accordance with the guidelines of the European Society of Cardiology19: patients with mild hypertension (140-159/90-99 mm Hg), moderate hypertension (160-179/100-109 mm Hg), and severe hypertension (≥180/≥110 mm Hg). Because dementia and stroke particularly predispose to the incidence of epilepsy, we identified these subgroups in the overall population to weight them equally in the groups (3 794 patients with dementia and 15 175 patients with stroke in each group).
Statistical Analysis
Differences in the sample characteristics between 4 antihypertensive drug classes were investigated using χ2 tests for categorical variables and Kruskal-Wallis tests for age. Conditional Cox regression models were used to assess the association between ARBs compared with all other antihypertensive drug classes as a group and each drug class separately. In addition, Cox regression models were prepared for each type of epilepsy separately, including focal (ICD-10 codes G40.0-G40.2), generalized (ICD-10 codes G40.3 and G40.4), other rare epilepsy syndromes (ICD-10 codes G40.5-G40.8), and unspecified epilepsy (ICD-10 code G40.9). Furthermore, a sensitivity analysis was conducted for all epilepsy diagnoses among patients without common risk factors for epilepsy (eg, cerebrovascular disease, Parkinson disease, dementia, and head injuries).
These analyses were repeated for 6 ARB drugs (losartan, valsartan, telmisartan, olmesartan, candesartan, irbesartan). Because of the large patient samples, 2-sided P < .01 was considered to be statistically significant. Analyses were conducted using SAS, version 9.4 (SAS Institute Inc).
Results
The study included 42 153 patients for each therapy class (168 612 patients total). The basic characteristics of the patients are displayed in Table 1. Because of the matched-pair study design, all 4 cohorts had the same age, sex, and comorbidity structure. The mean [SD] age was 62.3 [13.5] years; 21 667 (51.4%) were women and 20 486 (48.6%) were men. The prevalence of diabetes was 16.1% and cerebrovascular diseases was 3.6%, and Parkinson disease, dementia, and head injury were each diagnosed in less than 1% of patients.
Table 1. Basic Characteristics of Study Sample After Propensity Score Matchinga.
| Characteristic | Proportion of patients with hypertension (N = 168 612) | |||
|---|---|---|---|---|
| Treated with ACE inhibitors (n = 42 153) | Treated with β-blockers (n = 42 153) | Treated with CCBs (n = 42 153) | Treated with ARBs (n = 42 153) | |
| Age, mean (SD), y | 62.3 (13.5) | 62.3 (13.5) | 62.3 (13.5) | 62.3 (13.5) |
| Age, y | ||||
| ≤60 | 44.4 | 44.4 | 44.4 | 44.4 |
| 61-70 | 25.3 | 25.3 | 25.3 | 25.3 |
| 71-80 | 22.2 | 22.2 | 22.2 | 22.2 |
| >80 | 8.2 | 8.2 | 8.2 | 8.2 |
| Sex | ||||
| Female | 51.4 | 51.4 | 51.4 | 51.4 |
| Male | 48.6 | 48.6 | 48.6 | 48.6 |
| Diagnosis | ||||
| Cerebrovascular diseases | 3.6 | 3.6 | 3.6 | 3.6 |
| Parkinson disease | 0.6 | 0.6 | 0.6 | 0.6 |
| Dementia | 0.9 | 0.9 | 0.9 | 0.9 |
| Head injury | 0.6 | 0.6 | 0.6 | 0.6 |
Abbreviations: ARBs, angiotensin receptor blockers; ACE, angiotensin-converting enzyme; CCBs, calcium channel blockers.
For all characteristics, P > .99.
Cumulative Incidence of Epilepsy Diagnoses
Figure 2 shows the proportion of patients with a documented incident epilepsy diagnosis within 5 years after the index date. This proportion was at its lowest in patients treated with ARBs (0.27% at 1 year, 0.63% at 3 years, and 0.99% at 5 years) and at its 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; 1.47% for β-blockers and 1.48% for CCBs at 5 years). Of those patients with an epilepsy diagnosis, 10.8% had focal epilepsy, 5.6% had generalized epilepsy, 9.9% had other epilepsy, and 73.6% had unspecified epilepsy. In the substantially smaller groups with specific epilepsy syndromes, the lower hazard ratio (HR) observed with ARBs persisted, although the 95% CI included 1.0 (Table 2).
Figure 2. Proportion of Patients With Incident Epilepsy Diagnosis Treated With Different Antihypertensive Drugs.
ACE indicates angiotensin-converting enzyme; ARB, angiotensin receptor blocker; CCB, calcium channel blocker.
Table 2. Association Between Angiotensin Receptor Blockers and Incidence of Epilepsy Diagnoses in Patients in General Practices in Germany.
| ARBs vs all other antihypertensive drug classes, HR (95% CI)a | P value | ARBs vs β-blockers, HR (95% CI) | P value | ARBs vs CCBs, HR (95% CI) | P value | ARBs vs ACE inhibitors, HR (95% CI) | P value | |
|---|---|---|---|---|---|---|---|---|
| Type of drug | ||||||||
| All ARBs | 0.77 (0.65-0.90) | <.002 | 0.69 (0.57-0.83) | <.001 | 0.79 (0.65-0.97) | NA | 0.83 (0.68-1.02) | NA |
| Losartan | 0.44 (0.23-0.80) | <.007 | 0.40 (0.22-0.75) | <.004 | 0.43 (0.23-0.80) | <.008 | 0.48 (0.26-0.89) | NA |
| Valsartan | 0.87 (0.65-1.16) | NA | 0.80 (0.59-1.09) | NA | 0.87 (0.64-1.18) | NA | 0.96 (0.70-1.31) | NA |
| Telmisartan | 0.64 (0.36-1.16) | NA | 0.59 (0.34-1.05) | NA | 0.62 (0.35-1.10) | NA | 0.70 (0.39-1.24) | NA |
| Olmesartan | 0.86 (0.50-1.47) | NA | 0.79 (0.46-1.37) | NA | 0.89 (0.52-1.53) | NA | 0.97 (0.56-1.68) | NA |
| Candesartan | 0.81 (0.64-1.02) | NA | 0.73 (0.57-0.94) | NA | 0.80 (0.62-1.03) | NA | 0.87 (0.67-1.12) | NA |
| Irbesartan | 0.56 (0.25-1.28) | NA | 0.52 (0.23-1.19) | NA | 0.57 (0.25-1.30) | NA | 0.63 (0.28-1.45) | NA |
| Type of epilepsy | ||||||||
| Focal epilepsy | 0.70 (0.43-1.15) | NA | 0.78 (0.43-1.42) | NA | 0.72 (0.40-1.29) | NA | 0.60 (0.33-1.09) | NA |
| Generalized epilepsy | 0.45 (0.20-1.01) | NA | 0.45 (0.18-1.11) | NA | 0.40 (0.15-0.98) | NA | 0.53 (0.20-1.37) | NA |
| Other epilepsyb | 0.63 (0.36-1.10) | NA | 0.49 (0.26-0.92) | NA | 0.63 (0.34-1.17) | NA | 0.89 (0.44-1.79) | NA |
| Unspecified epilepsy | 0.82 (0.68-0.99) | NA | 0.72 (0.58-0.90) | <.004 | 0.87 (0.70-1.09) | NA | 0.89 (0.70-1.12) | NA |
Abbreviations: ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; CCBs, calcium channel blockers; HR, hazard ratio; NA, not applicable.
β-Blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers.
Other includes combined focal and generalized epilepsy, recurrent seizures, and rare epilepsy such as epilepsia partialis continua and Lance-Adams syndrome.
ARB Therapy, Incident Epilepsy, and Hypertension Severity
Angiotensin receptor blocker therapy was associated with a significantly decreased incidence of epilepsy (HR, 0.77; 95% CI, 0.65-0.90) compared with other antihypertensive medication classes as a group. An inverse association between the incidence of epilepsy and use of β-blockers was also observed. In drug-stratified analyses, the incidence of epilepsy was decreased with all ARB drugs; however, the association was significant only for losartan compared with β-blockers (HR, 0.40; 95% CI, 0.22-0.75; P < .01), CCBs (HR, 0.43; 95% CI, 0.23-0.80; P < .008), and all antihypertensive drug classes as a group (HR, 0.44; 95% CI, 0.23-0.80; P < .01) (Table 2).
Epilepsy has been found to be closely related to stroke20 and dementia.21 In the present study’s population, a previous diagnosis of stroke or dementia was associated with the occurrence of epilepsy (HR, 1.93; 95% CI, 1.65-2.67; P < .001 for stroke and HR, 1.66; 95% CI, 1.35-1.96; P < .001 for dementia). We investigated whether these diagnoses affected the association between ARBs and decreased incidence of epilepsy in the subgroup of patients who had a stroke or dementia before the initial diagnosis of epilepsy. In these patients, the association between ARBs and a decreased incidence of epilepsy was similar to that seen in the overall patient population (HR, 0.77; 95% CI, 0.65-0.89; P = .002). Among patients without the typical risk factors for epilepsy (eg, cerebrovascular disease, Parkinson disease, dementia, and head injuries), we observed similar associations: ARB therapy was associated with a significantly decreased incidence of epilepsy compared with other classes as a group (HR, 0.74; 95% CI, 0.65-0.85) and compared with β-blockers (HR, 0.72; 95% CI, 0.61-0.85) and CCBs (HR, 0.71; 95% CI, 0.60-0.83).
With regard to hypertension severity, there were no significant differences between intake of ARBs and the remaining drug groups. Compared with ARBs, the proportion of mild hypertension was higher in patients taking β-blockers, but there was no difference regarding severe hypertension (Table 3).
Table 3. Comparison of Hypertension Severity Between Patients Receiving Angiotensin Receptor Blockers and Other Drugs.
| Proportion of patients (n = 84 300) | |||||
|---|---|---|---|---|---|
| ARBs | All other antihypertensive drug classesa | P value for ARBs vs other antihypertensive drug classes | β-Blockers | P value for ARBs vs β-blockers | |
| Blood pressure values within 12 mo before or on index date | |||||
| Systolic, mean (SD), mm Hg | 147.8 (20.8) | 148.7 (21.4) | .07 | 144.0 (21.4) | <.001 |
| Diastolic, mean (SD), mm Hg | 87.4 (12.8) | 87.9 (12.4) | .10 | 86.2 (12.4) | <.001 |
| Hypertension groupb | |||||
| Mild | 65.1 | 63.7 | .08 | 71.5 | <.001 |
| Moderate | 23.6 | 24.1 | .48 | 18.5 | <.001 |
| Severe | 11.1 | 12.1 | .09 | 10.0 | .10 |
Abbreviation: ARBs, angiotensin receptor blockers.
β-Blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers.
Patients were placed into 3 groups based on hypertension guidelines of the European Society of Cardiology: mild hypertension, 140-159/90-99 mm Hg; moderate hypertension, 160-179/100-109 mm Hg; and severe hypertension, ≥180/≥110 mm Hg.
Discussion
This cohort study analyzed the association between the use of specific antihypertensive therapies and the new onset of epilepsy in a large cohort of patients with hypertension in Germany. Angiotensin receptor blocker therapy was associated with a decreased incidence of epilepsy compared with other antihypertensive drug classes (except ACE inhibitors). On analysis of individual drugs within the ARB drug class, only the use of losartan was associated with a statistically significant decrease in the incidence of epilepsy.
The association between arterial hypertension, which affects 20% to 45% of the adult population worldwide,19 and new onset of epilepsy is a novel field to be explored. Recent data show that arterial hypertension is one of the most common comorbidities of epilepsy. It is suspected that arterial hypertension may be a cause of seizures and epilepsy through direct or indirect mechanisms.7 For example, typical consequences of hypertension, such as stroke and small vessel disease, can cause brain lesions with the potential to induce epilepsy.7 Although no class of antihypertensive drugs has been shown to be superior in preventing cardiovascular events,22 it is conceivable that a reduced rate of stroke could be a mediator of the association between ARB intake and a reduced incidence of epilepsy. However, in the present study, when separately considering patients with stroke in the sample who subsequently developed epilepsy, we found that there was no significant difference in the association of ARB use and the incidence of epilepsy compared with the overall sample.
It has been postulated that the brain’s renin-angiotensin-aldosterone system plays a special mediating role in epilepsy pathology and may be associated with the hyperactivation of angiotensin II type 1 receptor and ACE signaling in astrocytes, oligodendrocytes, and microglia.23 Angiotensin receptor blockers act by blocking the angiotensin II type 1 receptors with concomitant stimulation of angiotensin II type 2 receptors and thus preventing the pathophysiologic factors mediated by the binding of angiotensin II to the type 1 receptor.
Numerous animal and in vitro studies in recent years indicate that ARBs, and losartan in particular, have primary antiepileptogenic and neuroprotective benefits. Various mechanisms could be involved in this process: angiotensin II and angiotensin I receptor expression is upregulated in models of epilepsy in rodents and expedites neuroinflammatory processes.24 By causing an angiotensin II type 1 receptor blockade, losartan can reduce neuronal loss and microglia-mediated inflammatory responses.25 Another important ARB-related mechanism is mediated via the TGFB signaling cascade: dysregulation of the TGFB pathway leads to abnormal cellular events and pathological hallmarks that are all part of neuronal pathology and epileptogenesis, such as breakdown of the blood-brain barrier, neuroinflammation, demyelination, synaptic loss, gliosis, and fibrosis.26
In resected hippocampus specimens from patients with hippocampal sclerosis, the relevant signaling molecules TGFB and TGFB receptor II as well as the downstream signaling molecule SMAD3 and phosphorylated SMAD3 were all substantially upregulated.27 Angiotensin receptor blockers downregulate the TGFB-mediated signaling cascade by preventing the phosphorylation of intracellular SMAD proteins and thereby displaying numerous neuroprotective benefits, such as diminishing neuroinflammation28 or reducing epilepsy severity and seizure frequency in a model of blood-brain barrier diffusion by albumin perfusion mimicking central nervous system insults.10 In rats undergoing amygdala kindling, use of losartan was associated with an increased threshold for stimuli-induced discharges and delayed onset of seizures.29 In a post–status epilepticus kainic acid model of temporal lobe epilepsy, losartan selectively displayed neuroprotective properties in the hippocampal CA1 region, favorably changed epilepsy-provoked behaviors, and was associated with reduced seizure frequency and duration.30 Some studies have found that losartan may be particularly effective in the modulation of epilepsy, evoking a plethora of benefits, both during the initial onset of epilepsy and also when spontaneous seizures chronify.8,10
These findings correspond with the results of the present study, which identified an association between use of losartan and a decreased incidence of epilepsy. These results allow the hypothesis that inhibition of the renin-angiotensin-aldosterone system may be associated with a reduced incidence of epilepsy over a long period of time. Although these findings do not prove causal associations, they point to the importance of antihypertensive drugs, especially the angiotensin antagonist group, in preventing secondary complications of arterial hypertension, such as epilepsy, and may be a new therapeutic option for epilepsy involving inhibition of the renin-angiotensin-aldosterone system. However, additional pathophysiologic studies are needed to further investigate this association. If future studies find a causal role of ARBs in the prevention of epilepsy, this finding may have the potential to change existing guidelines for the treatment of arterial hypertension.
Limitations
This study has limitations. First, the study was limited by its retrospective nature. Second, patients were not normalized with respect to the use of each class of antihypertensive drugs. All drug groups studied herein are considered first-line therapy for hypertension in accordance with the applicable guidelines.19 In practice, ACE inhibitors and β-blockers are most commonly prescribed as first-line therapy in Germany, followed by ARBs, CCBs, and diuretics.31 Third, prioritized prescription of ARBs for low-grade hypertension, which could represent a potential bias in our study, is not recommended by the guidelines and does not correspond with prescribing behavior in Germany. Fourth, the post hoc analysis (Table 3) does not indicate that patients with mild hypertension in the sample received ARBs in particular, making such a bias unlikely. Nevertheless, a prospective study with randomized allocation of drug groups would be a practical supplement to our study.
Fifth, we used the ICD-10 coding system, which sometimes involves misclassification and undercoding of certain diagnoses. Sixth, because the database does not offer data on the severity of cerebrovascular disease, we could not ensure that both groups were balanced in this regard. Data on mean blood pressure values were not available for all patients. Seventh, no data were available concerning the combined use of multiple antihypertensive drugs, which represents an interfering factor. In addition, no data on lifestyle factors, such as nicotine use or alcohol intake or social status, were available and could not be considered in the statistical analysis, especially in the propensity score matching. Other possible factors, such as genetic background, were not taken into account. In this regard, a possible bias cannot be ruled out with certainty. However, we believe that the broad database provides a good overview of general practitioner practices in Germany, and the association between ARBs and a decreased incidence of epilepsy that we identified may be important for the initiation of further studies on this issue.
Conclusion
In this cohort study, we found an association between decreased incidence of epilepsy in patients with hypertension and the use of ARB therapy. Additional research is needed on possible causal associations between hypertension and epilepsy and the signaling pathways involved in each. Findings of this study suggest that antihypertensive drugs may be a novel approach for preventing epilepsy in patients with arterial hypertension.
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