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1.
CNS Neurosci Ther ; 30(8): e14890, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39097910

ABSTRACT

AIMS: To explore the role of voltage-gated calcium channels (VGCC) in 5-HT2A/2C receptor agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride's improvement of spinal cord injury (SCI) induced detrusor sphincter dyssynergia and the expressions of the 5-hydroxy tryptamine (5-HT) 2A receptors and VGCCs in lumbosacral cord after SCI. METHODS: Female Sprague-Dawley rats were randomized into normal control group and SCI group (N = 15 each). Cystometrogram (CMG), simultaneous CMG, and external urethral sphincter electromyography (EUS-EMG) were conducted in all groups under urethane anesthesia. Drugs were administered intrathecally during CMG and EUS-EMG. Rats were euthanized and L6-S1 spinal cord were acquired for immunofluorescence. RESULTS: In SCI rats, intrathecal administration of 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride or L-type VGCC blocker, nifedipine, could significantly increase voiding volume, voiding efficiency, and the number of high-frequency oscillations. They could also prolong EUS bursting activity duration on EUS-EMG. Moreover, the effect of 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride can be eliminated with the combined administration of L-type VGCC agonist, (±)-Bay K 8644. No significant differences were observed in CMG after intrathecal administration of T-type VGCC blocker TTA-P2. Additionally, immunofluorescence of the lumbosacral cord in control and SCI rats showed that the 5-HT2A receptor and Cav1.2 immunolabeling-positive neurons in the anterior horn of the lumbosacral cord were increased in SCI rats. CONCLUSIONS: Our study demonstrated that 5-HT2A/2C agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride may improve SCI-induced DSD by inhibiting the L-type voltage-gated calcium channel in lumbosacral cord motoneurons.


Subject(s)
Calcium Channels, L-Type , Rats, Sprague-Dawley , Spinal Cord Injuries , Animals , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/complications , Female , Calcium Channels, L-Type/metabolism , Calcium Channels, L-Type/drug effects , Rats , Calcium Channel Blockers/pharmacology , Calcium Channel Blockers/therapeutic use , Receptor, Serotonin, 5-HT2A/metabolism , Receptor, Serotonin, 5-HT2A/drug effects , Amphetamines
2.
PLoS One ; 19(8): e0307258, 2024.
Article in English | MEDLINE | ID: mdl-39159218

ABSTRACT

BACKGROUND: Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. Patients with HFpEF are often elderly and their primary chronic symptom is severe exercise intolerance. Due to the frequent coexistence of hypertension in HFpEF patients, the use of anti-hypertensive medications is common in their treatment. While many cohort studies and several randomized controlled trials (RCTs) have examined the effectiveness of various anti-hypertensive drugs such as beta-blockers and renin-angiotensin system inhibitors in HFpEF, the role of calcium channel blockers (CCBs) remains uncertain. Despite several RCTs and cohort studies exploring the effects of CCBs on prognosis and exercise capacity in HFpEF patients, the findings have been inconsistent, likely due to limited statistical power and/or variations in study design. Therefore, our aim is to conduct a systematic review and meta-analysis of studies on the effects of CCBs in these patients. METHODS: This meta-analysis will include RCTs and cohort studies on the effect of CCBs in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, and Scopus. The primary outcome of interest will be prognosis. The secondary outcome of interest will be exercise capacity. DISCUSSION: Synthesizing our meta-analytical results with expert consensus could contribute to the formulation of updated clinical guidelines. Our systematic review and meta-analysis will provide directions for future research on the use of CCBs in HFpEF patients. SYSTEMATIC REVIEW REGISTRATION: INPLASY202430097.


Subject(s)
Calcium Channel Blockers , Heart Failure , Meta-Analysis as Topic , Stroke Volume , Systematic Reviews as Topic , Humans , Heart Failure/drug therapy , Heart Failure/physiopathology , Calcium Channel Blockers/therapeutic use , Stroke Volume/drug effects , Prognosis
3.
Int Immunopharmacol ; 138: 112586, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-38955030

ABSTRACT

Nimodipine, a calcium antagonist, exert beneficial neurovascular protective effects in clinic. Recently, Calcium channel blockers (CCBs) was reported to protect against liver fibrosis in mice, while the exact effects of Nimodipine on liver injury and hepatic fibrosis remain unclear. In this study, we assessed the effect of nimodipine in Thioacetamide (TAA)-induced liver fibrosis mouse model. Then, the collagen deposition and liver inflammation were assessed by HE straining. Also, the frequency and phenotype of NK cells, CD4+T and CD8+T cells and MDSC in liver and spleen were analyzed using flow cytometry. Furthermore, activation and apoptosis of primary Hepatic stellate cells (HSCs) and HSC line LX2 were detected using α-SMA staining and TUNEL assay, respectively. We found that nimodipine administration significantly attenuated liver inflammation and fibrosis. And the increase of the numbers of hepatic NK and NKT cells, a reversed CD4+/CD8+T ratio, and reduced the numbers of MDSC were observed after nimodipine treatment. Furthermore, nimodipine administration significantly decreased α-SMA expression in liver tissues, and increased TUNEL staining adjacent to hepatic stellate cells. Nimodipine also reduced the proliferation of LX2, and significantly promoted high level of apoptosis in vitro. Moreover, nimodipine downregulated Bcl-2 and Bcl-xl, simultaneously increased expression of JNK, p-JNK, and Caspase-3. Together, nimodipine mediated suppression of growth and fibrogenesis of HSCs may warrant its potential use in the treatment of liver fibrosis.


Subject(s)
Hepatic Stellate Cells , Killer Cells, Natural , Liver Cirrhosis , Liver , Mice, Inbred C57BL , Nimodipine , Thioacetamide , Animals , Nimodipine/pharmacology , Nimodipine/therapeutic use , Hepatic Stellate Cells/drug effects , Hepatic Stellate Cells/immunology , Liver Cirrhosis/drug therapy , Liver Cirrhosis/chemically induced , Liver Cirrhosis/pathology , Liver Cirrhosis/immunology , Mice , Liver/drug effects , Liver/pathology , Liver/immunology , Male , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Calcium Channel Blockers/pharmacology , Calcium Channel Blockers/therapeutic use , Apoptosis/drug effects , Humans , Disease Models, Animal , Cell Line , Cellular Microenvironment/drug effects , Myeloid-Derived Suppressor Cells/drug effects , Myeloid-Derived Suppressor Cells/immunology
4.
BMC Public Health ; 24(1): 1808, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971775

ABSTRACT

BACKGROUND: Single-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective. METHODS: A cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty. RESULTS: Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61-1.14), with a mean cost differential of -€12 (95% CI -9,719-8,131), making it the dominant strategy (ICER = -14, 95% CI -€15,871-€7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17-7,813) and €2,027 (95% CI 19-8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574-10,640 vs. €3,710, 95% CI 263-11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status. CONCLUSIONS: The SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.


Subject(s)
Antihypertensive Agents , Cost-Benefit Analysis , Hypertension , Humans , Antihypertensive Agents/economics , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/therapeutic use , Male , Female , Middle Aged , Aged , Italy , Hypertension/drug therapy , Adult , Drug Combinations , Angiotensin-Converting Enzyme Inhibitors/economics , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Calcium Channel Blockers/economics , Calcium Channel Blockers/therapeutic use , Calcium Channel Blockers/administration & dosage , Markov Chains , Drug Therapy, Combination , Aged, 80 and over , Computer Simulation , Diuretics/administration & dosage , Diuretics/economics , Diuretics/therapeutic use
5.
J Clin Neurosci ; 127: 110768, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39079423

ABSTRACT

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) patients are given calcium channel blockers (CCBs) to prevent brain vessel vasospasm. We hypothesized that preinjury antihypertensive use may protect against vasospasm. It remains unclear whether the timing of in-hospital CCB initiation affects the vasospasm risk in this population. METHODS: This retrospective cohort study included aSAH patients (≥18 y/o) at a Comprehensive Stroke Center (1/18-11/21). Patients taking prehospital antihypertensives [CCBs, Angiotensin-converting enzyme (ACE) inhibitors or Angiotensin II receptor blockers (ARBs)] were compared to those who were not. Results were stratified by patients receiving vasospasm prophylaxis ('in-hospital CCBs') ≤1.2 h of arrival vs. >1.2 h from arrival. Outcomes included vasospasm, hospital length of stay (LOS), and mortality. RESULTS: Of 251 patients, 18% were taking prehospital antihypertensives. Patients were comparable in baseline characteristics. There was no difference in the rate of vasospasm when compared by prehospital antihypertensive use. For those on prehospital antihypertensives, the time to in-hospital CCBs was significantly longer for patients who developed vasospasm than for those who did not (1.2 vs. 4.9 h, respectively, p = 0.02). For those on prehospital antihypertensives, receipt of in-hospital CCBs within 1.2 h of arrival was associated with a significantly lower vasospasm rate (6% vs. 39%, p = 0.03) and LOS (14 vs. 20 d, p = 0.01) when compared to receiving in-hospital CCBs > 1.2 h of arrival, respectively. The mortality rate (50% vs. 26%, p = 0.06) was statistically similar between groups, respectively. These results were not observed among patients who were not on prehospital antihypertensives. The timing to in-hospital CCB initiation had no effect on vasospasm (p = 0.23), death (p = 0.08), or LOS (p = 0.31) for patients not on prehospital antihypertensives. CONCLUSIONS: Enhancing the efficiency of in-hospital CCB initiation for patients on prehospital antihypertensives may decrease the occurrence of vasospasm and lead to a shorter LOS.


Subject(s)
Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Calcium Channel Blockers , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Humans , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/drug therapy , Vasospasm, Intracranial/etiology , Vasospasm, Intracranial/prevention & control , Female , Male , Middle Aged , Retrospective Studies , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/therapeutic use , Aged , Angiotensin Receptor Antagonists/administration & dosage , Angiotensin Receptor Antagonists/therapeutic use , Treatment Outcome , Adult , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/therapeutic use , Length of Stay/statistics & numerical data , Time Factors
6.
J Am Heart Assoc ; 13(15): e035177, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39056339

ABSTRACT

BACKGROUND: Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin-converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin-converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear. METHODS AND RESULTS: We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age 68 years [Q1 63, Q3 73]), of whom 1024 reached the trial end point over median follow-up of 2.8 years. Predictors of acute declines in eGFR>15% over 3 months included assignment to hydrochlorothiazide (versus amlodipine) and higher baseline albuminuria. Overall, declines in eGFR ≥15% (versus <15%) were associated with a 26% higher hazard of cardiovascular outcomes (95% CI, 1.07-1.48). In spline-based analysis, risk for cardiovascular outcomes was higher in the hydrochlorothiazide arm at every level of decline in eGFR compared with the same magnitude of eGFR decline in the amlodipine arm. CONCLUSION: Combined use of benazepril and amlodipine remains superior to benazepril and hydrochlorothiazide for cardiovascular outcomes, regardless of the magnitude of the decline in eGFR that occurred with initiation of therapy.


Subject(s)
Amlodipine , Angiotensin-Converting Enzyme Inhibitors , Antihypertensive Agents , Benzazepines , Drug Therapy, Combination , Glomerular Filtration Rate , Hydrochlorothiazide , Hypertension , Humans , Amlodipine/therapeutic use , Amlodipine/adverse effects , Hydrochlorothiazide/therapeutic use , Hydrochlorothiazide/adverse effects , Male , Female , Glomerular Filtration Rate/drug effects , Aged , Middle Aged , Benzazepines/therapeutic use , Benzazepines/adverse effects , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Hypertension/drug therapy , Hypertension/physiopathology , Hypertension/diagnosis , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/adverse effects , Treatment Outcome , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/epidemiology , Kidney/physiopathology , Kidney/drug effects , Time Factors , Risk Factors , Risk Assessment , Calcium Channel Blockers/therapeutic use , Calcium Channel Blockers/adverse effects
7.
Stroke ; 55(8): 2034-2044, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39038094

ABSTRACT

BACKGROUND: Recent hypertension guidelines for the general population have included race-specific recommendations for antihypertensives, whereas current stroke-specific recommendations for antihypertensives do not vary by race. The impact of these guidelines on antihypertensive regimen changes over time, and if this has varied by prevalent stroke status, is unclear. METHODS: The use of antihypertensive medications was studied cross-sectionally among self-identified Black and White participants, aged ≥45 years, with and without history of stroke, from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Participants completed an in-home examination in 2003-2007 (visit 1) with/without an examination in 2013-2016 (visit 2). Stratified by prevalent stroke status, logistic regression mixed models examined associations between antihypertensive class use for visit 2 versus visit 1 and Black versus White individuals with an interaction adjusted for demographics, socioeconomic status, and vascular risk factors/vital signs. RESULTS: Of 17 244 stroke-free participants at visit 1, Black participants had greater adjusted odds of angiotensin-converting enzyme inhibitor usage than White participants (odds ratio [OR], 1.51 [95% CI, 1.30-1.77]). This difference was smaller in the 7476 stroke-free participants at visit 2 (OR, 1.16 [95% CI, 1.08-1.25]). In stroke-free participants at visit 1, Black participants had lower odds of calcium channel blocker (CCB) usage than White participants (OR, 0.47 [95% CI, 0.41-0.55]), but CCB usage did not differ significantly between Black and White stroke-free participants at visit 2 (OR, 1.02 [95% CI, 0.95-1.09]). Among 1437 stroke survivor participants at visit 1, Black participants had lower odds of CCB use than White participants (OR, 0.34 [95% CI, 0.26-0.45]). In 689 stroke survivor participants at visit 2, CCB use did not differ between Black and White participants (OR, 0.80 [95% CI, 0.61-1.06]). CONCLUSIONS: Racial differences in the use of guideline-recommended antihypertensives decreased between 2003-2007 and 2013-2016 in stroke-free individuals. In stroke survivors, racial differences in CCB usage narrowed over the time periods. These findings suggest there is still a mismatch between race-specific hypertension guidelines and recent clinical practice.


Subject(s)
Antihypertensive Agents , Black or African American , Hypertension , Stroke , Aged , Female , Humans , Male , Middle Aged , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Cross-Sectional Studies , Hypertension/drug therapy , Hypertension/ethnology , Stroke/drug therapy , Stroke/ethnology , Stroke/epidemiology , White
8.
Cochrane Database Syst Rev ; 7: CD003598, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39082471

ABSTRACT

BACKGROUND: The comparative effects of specific blood pressure (BP) lowering treatments on patient-important outcomes following kidney transplantation are uncertain. Our 2009 Cochrane review found that calcium channel blockers (CCBs) improved graft function and prevented graft loss, while the evidence for other BP-lowering treatments was limited. This is an update of the 2009 Cochrane review. OBJECTIVES: To compare the benefits and harms of different classes and combinations of antihypertensive drugs in kidney transplant recipients. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 3 July 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating any BP-lowering agent in recipients of a functioning kidney transplant for at least two weeks were eligible. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risks of bias and extracted data. Treatment estimates were summarised using the random-effects model and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) processes. The primary outcomes included all-cause death, graft loss, and kidney function. MAIN RESULTS: Ninety-seven studies (8706 participants) were included. One study evaluated treatment in children. The overall risk of bias was unclear to high across all domains. Compared to placebo or standard care alone, CCBs probably reduce all-cause death (23 studies, 3327 participants: RR 0.83, 95% CI 0.72 to 0.95; I2 = 0%; moderate certainty evidence) and graft loss (24 studies, 3577 participants: RR 0.84, 95% CI 0.75 to 0.95; I2 = 0%; moderate certainty evidence). CCBs may make little or no difference to estimated glomerular filtration rate (eGFR) (11 studies, 2250 participants: MD 1.89 mL/min/1.73 m2, 95% CI -0.70 to 4.48; I2 = 48%; low certainty evidence) and acute rejection (13 studies, 906 participants: RR 10.8, 95% CI 0.85 to 1.35; I2 = 0%; moderate certainty evidence). CCBs may reduce systolic BP (SBP) (3 studies, 329 participants: MD -5.83 mm Hg, 95% CI -10.24 to -1.42; I2 = 13%; low certainty evidence) and diastolic BP (DBP) (3 studies, 329 participants: MD -3.98 mm Hg, 95% CI -5.98 to -1.99; I2 = 0%; low certainty evidence). CCBs have uncertain effects on proteinuria. Compared to placebo or standard care alone, angiotensin-converting-enzyme inhibitors (ACEi) may make little or no difference to all-cause death (7 studies, 702 participants: RR 1.13, 95% CI 0.58 to 2.21; I2 = 0%; low certainty evidence), graft loss (6 studies, 718 participants: RR 0.75, 95% CI 0.49 to 1.13; I2 = 0%; low certainty evidence), eGFR (4 studies, 509 participants: MD -2.46 mL/min/1.73 m2, 95% CI -7.66 to 2.73; I2 = 64%; low certainty evidence) and acute rejection (4 studies, 388 participants: RR 1.75, 95% CI 0.76 to 4.04; I2 = 0%; low certainty evidence). ACEi may reduce proteinuria (5 studies, 441 participants: MD -0.33 g/24 hours, 95% CI -0.64 to -0.01; I2 = 67%; low certainty evidence) but had uncertain effects on SBP and DBP. Compared to placebo or standard care alone, angiotensin receptor blockers (ARB) may make little or no difference to all-cause death (6 studies, 1041 participants: RR 0.69, 95% CI 0.36 to 1.31; I2 = 0%; low certainty evidence), eGRF (5 studies, 300 participants: MD -1.91 mL/min/1.73 m2, 95% CI -6.20 to 2.38; I2 = 57%; low certainty evidence), and acute rejection (4 studies, 323 participants: RR 1.00, 95% CI 0.44 to 2.29; I2 = 0%; low certainty evidence). ARBs may reduce graft loss (6 studies, 892 participants: RR 0.35, 95% CI 0.15 to 0.84; I2 = 0%; low certainty evidence), SBP (10 studies, 1239 participants: MD -3.73 mm Hg, 95% CI -7.02 to -0.44; I2 = 63%; moderate certainty evidence) and DBP (9 studies, 1086 participants: MD -2.75 mm Hg, 95% CI -4.32 to -1.18; I2 = 47%; moderate certainty evidence), but has uncertain effects on proteinuria. The effects of CCBs, ACEi or ARB compared to placebo or standard care alone on cardiovascular outcomes (including fatal or nonfatal myocardial infarction, fatal or nonfatal stroke) or other adverse events were uncertain. The comparative effects of ACEi plus ARB dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone were rarely evaluated. Head-to-head comparisons of ACEi, ARB or thiazide versus CCB, ACEi versus ARB, CCB or ACEi versus alpha- or beta-blockers, or ACEi plus CCB dual therapy versus ACEi or CCB monotherapy were scarce. No studies reported outcome data for cancer or life participation. AUTHORS' CONCLUSIONS: For kidney transplant recipients, the use of CCB therapy to reduce BP probably reduces death and graft loss compared to placebo or standard care alone, while ARB may reduce graft loss. The effects of ACEi and ARB compared to placebo or standard care on other patient-centred outcomes were uncertain. The effects of dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone and the comparative effects of different treatments were uncertain.


Subject(s)
Antihypertensive Agents , Calcium Channel Blockers , Hypertension , Kidney Transplantation , Randomized Controlled Trials as Topic , Humans , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Hypertension/drug therapy , Graft Survival/drug effects , Graft Rejection/prevention & control , Cause of Death , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Bias , Adult , Glomerular Filtration Rate/drug effects , Blood Pressure/drug effects
9.
Stroke ; 55(7): 1914-1922, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38860370

ABSTRACT

BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat. METHODS: Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age. RESULTS: Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (P=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (P<0.001) and more prompt responses (P<0.01), and less habituation upon repeated stimulation (P<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (P=0.015) and an increase in blood flow velocity (P=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (P<0.001) in the treated animals. CONCLUSIONS: Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.


Subject(s)
Calcium Channel Blockers , Cerebral Small Vessel Diseases , Cognition , Disease Models, Animal , Nimodipine , Rats, Inbred SHR , Animals , Nimodipine/pharmacology , Nimodipine/therapeutic use , Male , Cerebral Small Vessel Diseases/drug therapy , Rats , Cognition/drug effects , Calcium Channel Blockers/pharmacology , Calcium Channel Blockers/therapeutic use , Cerebrovascular Circulation/drug effects , Cognition Disorders/etiology , Cognition Disorders/drug therapy , Cognition Disorders/prevention & control
10.
J Assoc Physicians India ; 72(4): 54-58, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38881084

ABSTRACT

Calcium channel blockers (CCBs) are widely used antihypertensive agents due to their effectiveness in reducing blood pressure (BP), along with their good tolerability and evidence of reducing hypertension (HTN)-related cardiovascular and renal diseases. Cilnidipine, a unique dihydropyridine calcium antagonist, exhibits potent inhibitory action on both N-type and L-type voltage-dependent calcium channels. With excellent oral absorption and a prolonged duration of action, it demonstrates a significant antihypertensive effect. It effectively reduces BP both systolic and diastolic while providing renal, neurological, and cardiovascular protection. Unlike L-type CCBs, cilnidipine does not increase pulse rates (PRs) and is associated with reduced occurrence of pedal edema. Cilnidipine is an effective treatment choice for individuals with mild to moderate essential HTN, whether it is administered alone or in conjunction with other treatment modalities.


Subject(s)
Antihypertensive Agents , Calcium Channel Blockers , Dihydropyridines , Hypertension , Dihydropyridines/therapeutic use , Dihydropyridines/pharmacology , Humans , Calcium Channel Blockers/therapeutic use , Hypertension/drug therapy , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/pharmacology , Calcium Channels, N-Type/drug effects , Blood Pressure/drug effects , Calcium Channels, L-Type
11.
Medicine (Baltimore) ; 103(24): e37856, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38875375

ABSTRACT

BACKGROUND: Currently, most studies primarily focus on directly comparing the efficacy and safety of angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs), the two major classes of antihypertensive drugs. Moreover, the majority of studies are based on randomized controlled trials and traditional meta-analyses, with few exploring the efficacy and safety comparisons among various members of ACEIs and CCBs. METHODS: ACEIs and CCB were searched for in randomized controlled trials in CNKI, Wanfang, VIP, China Biology Medicine Disc (Si-noMed), PubMed, EMbase, and Cochrane Library databases. The search can be conducted till November 2022. Stata software (version 16.0) and R 4.1.3 was used for statistical analysis and graphics plotting, applying mvmeta, gemtc, and its packages. Meta-regression analysis was used to explore the inconsistencies of the studies. RESULTS: In 73 trials involving 33 different drugs, a total of 9176 hypertensive patients were included in the analysis, with 4623 in the intervention group and 4553 in the control group. The results of the analysis showed that, according to the SUCRA ranking, felodipine (MD = -12.34, 95% CI: -17.8 to -6.82) was the drug most likely to be the best intervention for systolic blood pressure, while nitrendipine (MD = -8.01, 95% CI: -11.71 to -4.18) was the drug most likely to be the best intervention for diastolic blood pressure. Regarding adverse drug reactions, nifedipine (OR = 0.32, 95% CI: 0.14-0.74) was the drug most likely to be the safest. CONCLUSION: The research findings indicate that nifedipine is the optimal intervention for reducing systolic blood pressure in hypertensive patients, nitrendipine is the optimal intervention for reducing diastolic blood pressure in hypertensive patients, and felodipine is the optimal intervention for safety.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Calcium Channel Blockers , Hypertension , Humans , Calcium Channel Blockers/therapeutic use , Hypertension/drug therapy , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Network Meta-Analysis , Antihypertensive Agents/therapeutic use , Randomized Controlled Trials as Topic , Treatment Outcome , Nifedipine/therapeutic use
12.
Blood Press ; 33(1): 2350981, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38824645

ABSTRACT

OBJECTIVE: Few studies have evaluated the performance of non-drug-adjusted primary aldosteronism (PA) screening. Therefore, we aimed to examine the consistency between PA screening results with and without drug adjustment and to explore the effectiveness of screening without drug adjustment. METHODS: This prospective study included 650 consecutive patients with a high risk of incidence PA. Patients who initially screened positive underwent rescreening with drug adjustments and confirmatory tests. Regarding the remaining patients, one of every three consecutive patients underwent rescreening with drug adjustments and confirmatory tests. The changes in aldosterone and renin concentrations were compared between patients with essential hypertension (EH) and those with PA before and after drug adjustment. Sensitivity and specificity were used to assess the diagnostic performance of screening without drug adjustment, using the confirmatory test results as the reference. RESULTS: We screened 650 patients with hypertension for PA. Forty-nine patients were diagnosed with PA and 195 with EH. Regarding drugs, 519 patients were taking angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), or diuretics alone or in combination. Forty-one patients were taking beta-blockers. Ninety patients were taking beta-blockers in combination with other drugs. In patients treated with ACEIs, ARBs, CCBs, or diuretics alone, or in combination, or beta-blockers alone, PA positivity was determined using the criteria, aldosterone-to-renin ratio (ARR) >38 pg/mL/pg/mL and plasma aldosterone concentration (PAC) >100 pg/mL, and negativity, using the criteria, ARR <9 pg/mL/pg/mL; the sensitivity and specificity were 94.7% and 94.5%, respectively. After drug adjustment, the sensitivity and specificity of screening were 92.1% and 89%, respectively. CONCLUSIONS: In patients not treated with beta-blockers combined with others, when ARR >38 pg/mL/pg/mL and plasma aldosterone concentration (PAC) >100 pg/mL, or, ARR <9 pg/mL/pg/mL, non-drug-adjusted screening results were identical to with drug adjustment. Non-drug-adjusted screening could reduce the chance of medication adjustment, enable patients to continue their treatments and avoiding adverse effects, is of clinical importance.


Primary aldosteronism (PA) is the most common form of endocrine hypertension. The risk of stroke, myocardial infarction, heart failure, atrial fibrillation, and deterioration of kidney function is higher in PA than in essential hypertension (EH), even with the same blood pressure (BP) levels. However, many patients remain undiagnosed because most antihypertensive drugs substantially interfere with PA screening results, which makes drug adjustment necessary. This can be a time-consuming and unsafe process, requiring 4­6 weeks, and could lead to a hypertensive crisis and other complications. Some studies have suggested that certain antihypertensive drugs can be continued during PR screening. However, few studies have evaluated the performance of non-drug-adjusted PA screening. Therefore, in this prospective study, we aimed to compare patients with hypertension and a high risk of PA before and after drug adjustment and to use confirmatory test results as a reference to explore the diagnostic or exclusion effect. We found that non-drug-adjusted screening performs similarly to drug-adjusted screening in a particular group of patients. Our findings could aid in preventing unnecessary drug adjustment for PA screening, thereby reducing the risk in these patients.


Subject(s)
Aldosterone , Hyperaldosteronism , Humans , Hyperaldosteronism/diagnosis , Hyperaldosteronism/blood , Hyperaldosteronism/drug therapy , Female , Middle Aged , Male , Prospective Studies , Aldosterone/blood , Renin/blood , Adult , Calcium Channel Blockers/therapeutic use , Hypertension/drug therapy , Hypertension/blood , Hypertension/diagnosis , Antihypertensive Agents/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Mass Screening/methods , Aged , Angiotensin Receptor Antagonists/therapeutic use
13.
Eur J Pharmacol ; 977: 176718, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38849040

ABSTRACT

Nimodipine is used to prevent delayed ischemic deficit in patients with aneurysmal subarachnoid hemorrhage (aSAH). Spreading depolarization (SD) is recognized as a factor in the pathomechanism of aSAH and other acute brain injuries. Although nimodipine is primarily known as a cerebral vasodilator, it may have a more complex mechanism of action due to the expression of its target, the L-type voltage-gated calcium channels (LVGCCs) in various cells in neural tissue. This study was designed to investigate the direct effect of nimodipine on SD, ischemic tissue injury, and neuroinflammation. SD in control or nimodipine-treated live mouse brain slices was induced under physiological conditions using electrical stimulation, or by subjecting the slices to hypo-osmotic stress or mild oxygen-glucose deprivation (mOGD). SD was recorded applying local field potential recording or intrinsic optical signal imaging. Histological analysis was used to estimate tissue injury, the number of reactive astrocytes, and the degree of microglia activation. Nimodipine did not prevent SD occurrence in mOGD, but it did reduce the rate of SD propagation and the cortical area affected by SD. In contrast, nimodipine blocked SD occurrence in hypo-osmotic stress, but had no effect on SD propagation. Furthermore, nimodipine prevented ischemic injury associated with SD in mOGD. Nimodipine also exhibited anti-inflammatory effects in mOGD by reducing reactive astrogliosis and microglial activation. The results demonstrate that nimodipine directly inhibits SD, independent of nimodipine's vascular effects. Therefore, the use of nimodipine may be extended to treat acute brain injuries where SD plays a central role in injury progression.


Subject(s)
Brain Ischemia , Brain , Cortical Spreading Depression , Nimodipine , Animals , Nimodipine/pharmacology , Mice , Cortical Spreading Depression/drug effects , Male , Brain/drug effects , Brain/pathology , Brain/metabolism , Brain Ischemia/drug therapy , Brain Ischemia/pathology , Mice, Inbred C57BL , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/pathology , Microglia/drug effects , Microglia/metabolism , Microglia/pathology , Calcium Channel Blockers/pharmacology , Calcium Channel Blockers/therapeutic use , Osmotic Pressure/drug effects
14.
BMJ ; 385: e079108, 2024 06 19.
Article in English | MEDLINE | ID: mdl-38897628

ABSTRACT

Resistant hypertension is defined as blood pressure that remains above the therapeutic goal despite concurrent use of at least three antihypertensive agents of different classes, including a diuretic, with all agents administered at maximum or maximally tolerated doses. Resistant hypertension is also diagnosed if blood pressure control requires four or more antihypertensive drugs. Assessment requires the exclusion of apparent treatment resistant hypertension, which is most often the result of non-adherence to treatment. Resistant hypertension is associated with major cardiovascular events in the short and long term, including heart failure, ischemic heart disease, stroke, and renal failure. Guidelines from several professional organizations recommend lifestyle modification and antihypertensive drugs. Medications typically include an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, a calcium channel blocker, and a long acting thiazide-type/like diuretic; if a fourth drug is needed, evidence supports addition of a mineralocorticoid receptor antagonist. After a long pause since 2007 when the last antihypertensive class was approved, several novel agents are now under active development. Some of these may provide potent blood pressure lowering in broad groups of patients, such as aldosterone synthase inhibitors and dual endothelin receptor antagonists, whereas others may provide benefit by allowing treatment of resistant hypertension in special populations, such as non-steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease. Several device based approaches have been tested, with renal denervation being the best supported and only approved interventional device treatment for resistant hypertension.


Subject(s)
Antihypertensive Agents , Hypertension , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/therapy , Antihypertensive Agents/therapeutic use , Drug Resistance , Drug Therapy, Combination , Calcium Channel Blockers/therapeutic use , Blood Pressure/drug effects , Blood Pressure/physiology
15.
J Drugs Dermatol ; 23(6): 446-449, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38834225

ABSTRACT

Acne vulgaris is a common chronic dermatological condition characterized by obstruction and inflammation of pilosebaceous units. Recent research on a different dermatologic condition has demonstrated that the use of vasodilatory medications is associated with a decreased relative risk of rosacea. This finding is significant due to the overlapping inflammatory pathways involved in rosacea and acne. Herein, a retrospective cohort study was designed to determine the correlation between vasodilator usage and the risk of developing acne within 5 years, contrasting it with thiazide diuretics, chosen as a control due to its non-vasodilatory antihypertensive mechanism and availability of data. Angiotensin-converting enzyme (ACE) inhibitors (RR, 0.775; 95% CI, 0.727-0.826; P<0.05), angiotensin receptor blockers (ARBs) (RR, 0.739; 95% CI, 0.685-0.797; P<0.05), beta-blockers (BB) (RR, 0.829; 95% CI, 0.777-0.885; P<0.05), and calcium channel blockers (CCB) usage (RR, 0.821, 95% CI, 0.773-0.873; P<0.05) were associated with a significantly lower risk of developing acne within 5 years of initiating therapy compared to thiazide diuretics. It is unclear if thiazide diuretics are more likely to cause acne within the adult population or if vasodilators are protective against the development of acne. Finding mechanisms and therapeutics that lower the risk of developing acne is of significant public health interest, and this study provides a step toward this endeavor. Further research is required to uncover the underlying mechanisms for this reduction in the development of acne.  J Drugs Dermatol. 2024;23(6):446-449.     doi:10.36849/JDD.8362.


Subject(s)
Acne Vulgaris , Vasodilator Agents , Humans , Acne Vulgaris/drug therapy , Acne Vulgaris/epidemiology , Retrospective Studies , Male , Adult , Female , Vasodilator Agents/administration & dosage , Middle Aged , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Sodium Chloride Symporter Inhibitors/therapeutic use , Sodium Chloride Symporter Inhibitors/adverse effects , Calcium Channel Blockers/therapeutic use , Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/adverse effects , Young Adult , Angiotensin Receptor Antagonists/adverse effects , Angiotensin Receptor Antagonists/administration & dosage , Angiotensin Receptor Antagonists/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Adrenergic beta-Antagonists/adverse effects
16.
Blood Press ; 33(1): 2368800, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38910347

ABSTRACT

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.


What is the context? Hypertension is a strong independent risk factor for development of chronic kidney disease (CKD) and progression of CKD to ESKD. Improved adherence to the guidelines in the treatment of CKD is believed to provide further reduction of cardiorenal events. European Society of Hypertension Excellence Centres (ESH-ECs) have been developed in Europe to provide excellency regarding management of patients with hypertension and implement guidelines. Numerous deficits regarding general practitioner CKD screening, use of nephroprotective drugs and referral to nephrologists prior to referral to ESH-ECs have been reported. In contrast, real-life management of these patients among ESH-ECs is unknown. Before implementation of strategies to improve guideline adherence in Europe, we aimed to investigate how patients with CKD are managed among the ESH-ECs.What is the study about? In this study, a survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-ECs. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed among their centres.What are the results? RAAS blockers are initiated in 90% of ESH-ECs in CKD patients, but the initiation of MRA and SGLT2i is less frequently done. Hyperkalemia is the main barrier for initiation or adequate dosing of RAAS blockade, and its most reported management was RAAS blockers dosage reduction. These findings will be crucial to implement strategies in order to improve management of patients with CKD and guideline adherence among ESH-ECs.


Subject(s)
Hypertension , Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Hypertension/drug therapy , Europe , Antihypertensive Agents/therapeutic use , Male , Surveys and Questionnaires , Female , Middle Aged , Calcium Channel Blockers/therapeutic use , Societies, Medical , Angiotensin Receptor Antagonists/therapeutic use
18.
Kardiologiia ; 64(5): 26-32, 2024 May 31.
Article in Russian | MEDLINE | ID: mdl-38841786

ABSTRACT

Based on a clinical case report, the article shows the individual selection of effective therapy for a patient with arterial hypertension and dyslipidemia. Taking into account the risk factors for cardiovascular diseases, Equamer® was selected as a fixed combination of amlodipine + lisinopril + rosuvastatin capsules 10 mg+20 mg+10 mg (Gedeon Richter Plc, Budapest, Hungary). In the patient with hypertension, ischemic heart disease was verified, and stenting of the anterior descending artery was performed. According to the clinical guidelines, when arterial hypertension is associated with ischemic heart disease, the drug therapy of choice should be a combination of dihydropyridine slow calcium channel blockers with an angiotensin-converting enzyme inhibitor. The fixed triple combination of amlodipine, lisinopril, and rosuvastatin is one of the most appropriate in this clinical situation; this combination targets the two major risk factors for cardiovascular diseases, arterial hypertension and dyslipidemia.


Subject(s)
Amlodipine , Drug Combinations , Dyslipidemias , Hypertension , Humans , Amlodipine/administration & dosage , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Dyslipidemias/drug therapy , Dyslipidemias/complications , Hypertension/drug therapy , Lisinopril/administration & dosage , Lisinopril/therapeutic use , Rosuvastatin Calcium/administration & dosage , Rosuvastatin Calcium/therapeutic use , Treatment Outcome
19.
Curr Probl Cardiol ; 49(9): 102669, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38823526

ABSTRACT

Atrial fibrillation (AF) is common, but there are limited data to guide selection of rate control medications (RCM). Reasons for selection are multivariable, and the impact on outcomes is unknown. We investigated prescribing patterns of RCM among patients with AF. Using a nationwide database, we identified 135,927 patients with AF. We stratified by baseline presence of heart failure with reduced ejection fraction (HFrEF) and examined prescription rates of RCM as a function of clinical variables. We also evaluated associations with clinical outcomes. Beta blockers (BB) were most commonly prescribed (44.6%), then calcium channel blockers (CCB) (14.0%) and digoxin (8.6%). Patients prescribed BB were more likely male (45.6% vs 43.4%, p < 0.0001), patients prescribed CCB were less likely male (12.0% vs 16.3%, p < 0.0001). There were higher rates of HF hospitalization (HFH) among females and those with Medicaid. Randomized trials are needed to define optimal choice of RCM.


Subject(s)
Adrenergic beta-Antagonists , Anti-Arrhythmia Agents , Atrial Fibrillation , Calcium Channel Blockers , Practice Patterns, Physicians' , Humans , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Female , Male , Aged , Practice Patterns, Physicians'/statistics & numerical data , Anti-Arrhythmia Agents/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , United States/epidemiology , Middle Aged , Calcium Channel Blockers/therapeutic use , Digoxin/therapeutic use , Heart Rate/physiology , Heart Rate/drug effects , Heart Failure/epidemiology , Heart Failure/drug therapy , Heart Failure/physiopathology , Treatment Outcome , Hospitalization/statistics & numerical data , Retrospective Studies , Databases, Factual , Aged, 80 and over , Stroke Volume/physiology
20.
JAMA Neurol ; 81(8): 866-874, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38884986

ABSTRACT

Importance: Animal and human studies have suggested that the use of angiotensin receptor blockers (ARBs) may be associated with a lower risk of incident epilepsy compared with other antihypertensive medications. However, observational data from the US are lacking. Objective: To evaluate the association between ARB use and epilepsy incidence in subgroups of US patients with hypertension. Design, Setting, and Participants: This retrospective cohort study used data from a national health administrative database from January 2010 to December 2017 with propensity score (PS) matching. The eligible cohort included privately insured individuals aged 18 years or older with diagnosis of primary hypertension and dispensed at least 1 ARB, angiotensin-converting enzyme inhibitor (ACEI), ß-blocker, or calcium channel blocker (CCB) from 2010 to 2017. Patients with a diagnosis of epilepsy at or before the index date or dispensed an antiseizure medication 12 months before or 90 days after initiating the study medications were excluded. The data analysis for this project was conducted from April 2022 to April 2024. Exposures: Propensity scores were generated based on baseline covariates and used to match patients who received ARBs with those who received either ACEIs, ß-blockers, CCBs, or a combination of these antihypertensive medications. Main Outcomes and Measures: Cox regression analyses were used to evaluate epilepsy incidence during follow-up comparing the ARB cohort with other antihypertensive classes. Subgroup and sensitivity analyses were conducted to examine the association between ARB use and epilepsy incidence in various subgroups. Results: Of 2 261 964 patients (mean [SD] age, 61.7 [13.9] years; 1 120 630 [49.5%] female) included, 309 978 received ARBs, 807 510 received ACEIs, 695 887 received ß-blockers, and 448 589 received CCBs. Demographic and clinical characteristics differed across the 4 comparison groups prior to PS matching. Compared with ARB users, patients receiving ACEIs were predominantly male and had diabetes, CCB users were generally older (eg, >65 years), and ß-blocker users had more comorbidities and concurrent medications. The 1:1 PS-matched subgroups included 619 858 patients for ARB vs ACEI, 619 828 patients for ARB vs ß-blocker, and 601 002 patients for ARB vs CCB. Baseline characteristics were equally distributed between comparison groups after matching with propensity scores. Use of ARBs was associated with a decreased incidence of epilepsy compared with ACEIs (adjusted hazard ratio [aHR], 0.75; 95% CI, 0.58-0.96), ß-blockers (aHR, 0.70; 95% CI, 0.54-0.90), and a combination of other antihypertensive classes (aHR, 0.72; 95% CI, 0.56-0.95). Subgroup analyses revealed a significant association between ARB use (primarily losartan) and epilepsy incidence in patients with no preexisting history of stroke or cardiovascular disease. Conclusions and Relevance: This cohort study found that ARBs, mainly losartan, were associated with a lower incidence of epilepsy compared with other antihypertensive agents in hypertensive patients with no preexisting stroke or cardiovascular disease. Further studies, such as randomized clinical trials, are warranted to confirm the comparative antiepileptogenic properties of antihypertensive medications.


Subject(s)
Angiotensin Receptor Antagonists , Epilepsy , Hypertension , Humans , Female , Hypertension/epidemiology , Hypertension/drug therapy , Male , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin Receptor Antagonists/adverse effects , Middle Aged , Epilepsy/drug therapy , Epilepsy/epidemiology , Retrospective Studies , Aged , Adult , Antihypertensive Agents/therapeutic use , Incidence , Cohort Studies , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Propensity Score , Calcium Channel Blockers/therapeutic use , Calcium Channel Blockers/adverse effects , United States/epidemiology
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