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Purpose: Hydrochlorothiazide (HCTZ) exposure has been linked to increased skin cancer in Caucasian (white) populations, especially squamous cell carcinoma (SCC), but not basal cell carcinoma (BCC). This study aimed to evaluate and compare skin cancer risks associated with HCTZ‐ and other antihypertensives use. Methods: This retrospective cohort study utilized Taiwan's National Health Insurance Research Database. We identified patients aged 20 years and older, newly receiving antihypertensive medications between 2004 and 2015. We calculated the medication possession ratio (MPR) for the first 2 years of treatment to determine patient eligibility and treatment classification, whereby only patients with MPR above 80% were included. These were subsequently categorized by the type of antihypertensives they received, namely HCTZ, other thiazide diuretics, non‐thiazide diuretics or non‐diuretic antihypertensives. Cox proportional hazards model was used to evaluate skin cancer risks, and these were then classified as SCC or BCC. Results: Our study included 41 086, 27 402, 19 613, and 856 782 patients receiving HCTZ, other thiazide diuretics, non‐thiazide diuretics, and non‐diuretic antihypertensives, respectively. We found BCC risks were similar when comparing HCTZ with other thiazides (adjusted hazard ratio: 0.84; 95% CI: 0.54–1.33), non‐thiazide diuretics (0.93; 0.51–1.67), and non‐diuretic antihypertensives (0.91; 0.66–1.26). We observed a higher SCC risk in the HCTZ group, compared to other thiazides (1.24; 0.74–2.08), non‐thiazide diuretics (1.32; 0.70–2.51), and non‐diuretic antihypertensives (1.23; 0.87–1.73), although the confidence intervals (CIs) were wide and crossed the null. Conclusions: We concluded that skin cancer need not be of major concern to physicians when prescribing antihypertensives for an Asian population. [ABSTRACT FROM AUTHOR]

Fixed-dose combination therapy is considered a practical approach in the treatment of various diseases, as it can simultaneously target different mechanisms of action that achieve the required therapeutic efficacy through a synergistic effect. A combination of hydrochlorothiazide (HTZ), amlodipine (AMD), and valsartan (VLS) has been created for the treatment of hypertension. Therefore, the aim of this study was to develop an optimized UPLC method for the simultaneous quantification of this combination. A DoE at a level of 32 was used to investigate the effects of column temperature (20, 30, and 40 °C) and formic acid concentration (0.05, 0.15, and 0.25%) on the retention time of each active pharmaceutical ingredient (API), the peak area, and the peak symmetry, as well as the resolution between HTZ-AMD and AMD-VLS peaks. The optimized analytical method was validated and used to extract the three APIs from the marketed product. The optimized analytical condition with a column temperature of 27.86 °C and a formic acid concentration of 0.172% showed good separation of the three APIs in 1.62 ± 0.006, 3.59 ± 0.002, and 3.94 ± 0.002 min for HTZ, AMD, and VST, respectively. The developed method was linear with the LOQ for a HTC, AMD, and VST of 0.028, 0.038, and 0.101 ppm, respectively. Moreover, the developed assay was sustainable and robust, with an RSD % of less than 2%. The application of this method in the extraction of HTZ, AMD, and VST from the Exforge® marketed product showed good separation with a measurable drug content of 23.5 ± 0.7, 9.68 ± 0.1, and 165.2 ± 5.2 mg compared to the label claims of 25/10/160 for HTZ, AMD, and VST, respectively. [ABSTRACT FROM AUTHOR]

Currently, only the general control of the risk factors is known to prevent lacunar cerebral infarction, but it is unknown which type of medication for controlling the risk factors has a causal relationship with reducing the risk of lacunar infarction. To unlock this medical mystery, drug-target Mendelian randomization analysis was applied to estimate the effect of common antihypertensive agents, hypolipidemic agents, and hypoglycemic agents on lacunar stroke. Lacunar stroke data for the transethnic analysis were derived from meta-analyses comprising 7338 cases and 254,798 controls. We have confirmed that genetic variants mimicking calcium channel blockers were found to most stably prevent lacunar stroke. The genetic variants at or near HMGCR, NPC1L1, and APOC3 were predicted to decrease lacunar stroke incidence in drug-target MR analysis. These variants mimic the effects of statins, ezetimibe, and antisense anti-apoC3 agents, respectively. Genetically proxied GLP1R agonism had a marginal effect on lacunar stroke, while a genetically proxied improvement in overall glycemic control was associated with reduced lacunar stroke risk. Here, we show that certain categories of drugs currently used in clinical practice can more effectively reduce the risk of stroke. Repurposing several drugs with well-established safety and low costs for lacunar stroke prevention should be given high priority when doctors are making decisions in clinical practice. This may contribute to healthier brain aging. [ABSTRACT FROM AUTHOR]

Background: Antihypertensive agents used during pregnancy may vary from institution to institution and depend on resource availability. Objective: This study aimed to determine the profile of antihypertensive drugs used in pregnancy in low-middle-income countries and the impact of these drugs on maternal and fetal outcomes. Materials and Methods: This is a retrospective study on hypertensive pregnant patients admitted to the emergency unit at a tertiary referral Hospital in Indonesia. The type of hypertension during pregnancy, antihypertensive drugs, side effect, and maternal and perinatal outcomes was extracted from medical hospital records. Results: A total of 762 hypertensive pregnant women were recruited; 61 were diagnosed with preeclampsia, 491 were preeclampsia with severe features and 174 were chronic hypertension superimposed preeclampsia, and 81.54% of them received antihypertension therapy. The most commonly prescribed antihypertensive drugs were combination therapy of nifedipine and methyldopa (96.7%), followed by monotherapy of methyldopa (2.3%), nicardipine (1.1%), and nifedipine (0.2%). Most of the patients successfully attained a Systolic blood pressure<160mmHg. Tachycardia was reported in 47 (7.9%) pregnant women who received antihypertensive medication; none reported hypotension and arrhythmia. Conclusion: Nifedipine and methyldopa are choices for an antihypertensive agent in limited resources, either monotherapy or combined. Nifedipine's immediate release can be used with a low risk of hypotension. [ABSTRACT FROM AUTHOR]

Hypertension is a prevalent cardiovascular condition that affects millions of people worldwide. It is characterized by abnormally high blood pressure in the arteries, leading to an increased risk of heart disease, stroke, and kidney failure. Hypertension management often involves the use of pharmaceutical drugs, which can have adverse side effects. Hence, there is a growing interest in alternative therapies, such as herbal medicine, for the management of hypertension. This present study investigated the cardioprotective properties of moringa (Moringa oleifera) and mucuna (Mucuna pruriens L.) seeds at 5 and 10% dietary inclusions and also establish the most potent seed. The blood pressure of the rats were measured at the last day of treatment. Also, the heart acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities were determined, as well as the redox status of the rats. This study shows a reduction in blood pressure, AChE and MAO activities of hypertensive rats treated with the moringa and mucuna seeds. Furthermore, an increase in non-protein thiol (NP-SH) with a concomitant reduction in level of lipid peroxidation was also recorded. In addition, the mucuna seed is recorded to have a more cardioprotective property when compared with moringa seed. This study, therefore, revealed the mechanism of action of moringa seed and mucuna seed against l-NAME-induced hypertension or cardiotoxicity which could be linked to the antioxidant activity and modulation of AChE and MAO activities.

Currently, only the general control of the risk factors is known to prevent lacunar cerebral infarction, but it is unknown which type of medication for controlling the risk factors has a causal relationship with reducing the risk of lacunar infarction. To unlock this medical mystery, drug-target Mendelian randomization analysis was applied to estimate the effect of common antihypertensive agents, hypolipidemic agents, and hypoglycemic agents on lacunar stroke. Lacunar stroke data for the transethnic analysis were derived from meta-analyses comprising 7338 cases and 254,798 controls. We have confirmed that genetic variants mimicking calcium channel blockers were found to most stably prevent lacunar stroke. The genetic variants at or near HMGCR, NPC1L1, and APOC3 were predicted to decrease lacunar stroke incidence in drug-target MR analysis. These variants mimic the effects of statins, ezetimibe, and antisense anti-apoC3 agents, respectively. Genetically proxied GLP1R agonism had a marginal effect on lacunar stroke, while a genetically proxied improvement in overall glycemic control was associated with reduced lacunar stroke risk. Here, we show that certain categories of drugs currently used in clinical practice can more effectively reduce the risk of stroke. Repurposing several drugs with well-established safety and low costs for lacunar stroke prevention should be given high priority when doctors are making decisions in clinical practice. This may contribute to healthier brain aging.

OBJECTIVES In observational studies, the methods used to measure medication adherence may affect assessments of the clinical outcomes of drug therapy. This study estimated medication adherence to multidrug therapy in patients with hypertension using different measurement methods and compared their impacts on clinical outcomes. METHODS This was a retrospective cohort study using the Korean National Health Insurance Service–National Sample Cohort database (2006-2015). Adults diagnosed with hypertension who initiated multidrug antihypertensive therapy in the index year 2007 were included. Adherence was defined as over 80% compliance. Adherence to multidrug antihypertensive therapy was measured in 3 ways using the proportion of days covered (PDC) with 2 approaches to the end-date of the study observations: PDC with at least one drug (PDCwith≥1), PDC with a duration weighted mean (PDCwm), and the daily polypharmacy possession ratio (DPPR). The primary clinical outcome was a composite of cardiovascular and cerebrovascular disease-specific hospitalizations or all-cause mortality. RESULTS In total, 4,226 patients who initiated multidrug therapy for hypertension were identified. The mean adherence according to the predefined measurements varied from 72.7% to 79.8%. Non-adherence was associated with an increased risk of a primary outcome. The hazard ratios (95% confidence intervals, CIs) primary outcomes varied from 1.38 (95% CI, 1.19 to 1.59) to 1.44 (95% CI, 1.25 to 1.67). CONCLUSIONS Non-adherence to multidrug antihypertensive therapy was significantly associated with an increased risk of a primary clinical outcome. Across the varying estimates based on different methods, medication adherence levels were similar. These findings may provide evidence to support decision-making when assessing medication adherence.

Introduction: The incidence of hypertension among neonates admitted to the Neonatal Intensive Care Unit (NICU) is increasing. The reported incidence is between 0.2% and 3%. Blood Pressure (BP) among neonates varies considerably in the immediate postnatal period. The BP in neonates determined by birthweight, gestational age at birth and postnatal age. This variability in BP makes it challenging to diagnose neonatal hypertension. There is a paucity of Indian studies on neonatal hypertension. A systematic diagnostic evaluation of neonatal hypertension aids in early identification of the aetiology and further management. Aim: To assess the incidence of hypertension in neonates in the NICU and to evaluate the aetiology and clinical profile of neonatal hypertension. Materials and Methods: This was a hospital-based prospective observational study done at Sri Dharmasthala Manjunatheswara College of Medical Sciences and Hospital, Dharwad, Karnataka, India, between August 2016 and August 2021. A total of 29 neonates who had neonatal hypertension were included in the study after obtaining ethical committee clearance. All relevant data regarding demographic details, risk factors for hypertension, clinical features, probable aetiology, and relevant investigations were collected in a predesigned proforma. These neonates were followed- up once a month until six months of age. All the data were entered in Microsoft Excel version 2203 and analysed using the Statistical Package for Social Sciences (SPSS) software version 20.0. The categorical variables were described as percentages. The numerical variables were compared using a Student’s t-test and a Chi-square test. A p-value of 0.05 was considered statistically significant. Results: In the present study, out of 13,345, a total of 29 (0.22%) neonates had hypertension. Hypertension was more prevalent among term (82.7%). Of the 29 neonates, 19 (65.5%) had an antenatal risk for hypertension. A total of 14 (48.3%) of neonates had an antenatally diagnosed renal and/or cardiac anomaly. The most common presentation of hypertension is asymptomatic. Thirteen (44.8%) neonates had transient hypertension, which resolved at the time of discharge, and 16 (55.2%) neonates had persistent hypertension, requiring antihypertensive medication and follow-up. The most common aetiology for hypertension was renal and renovascular causes (44.8%). Mortality in the present study was 10.3% (n=3). Conclusion: Hypertension is an uncommon yet important problem in the NICU. In the majority of neonates, the presentation of hypertension is asymptomatic. Most common aetiology of hypertension being renal cause. Neonates with persistent hypertension may require long-term antihypertensive treatment and regular follow-up.

Although the majority of individuals with hypertension (HTN) have primary and polygenic HTN, monogenic HTN is a secondary type that is widely thought to play a key role in pediatric HTN, which has the characteristics of early onset, refractory HTN with a positive family history, and electrolyte disorders. Monogenic HTN results from single genetic mutations that contribute to the dysregulation of blood pressure (BP) in the kidneys and adrenal glands. It is pathophysiologically associated with increased sodium reabsorption in the distal tubule, intravascular volume expansion, and HTN, as well as low renin and varying aldosterone levels. Simultaneously increased or decreased potassium levels also provide clues for the diagnosis of monogenic HTN. Discovering the genetic factors that cause an increase in BP has been shown to be related to the choice of and responses to antihypertensive medications. Therefore, early and precise diagnosis with genetic sequencing and effective treatment with accurate antihypertensive agents are critical in the management of monogenic HTN. In addition, understanding the genetic architecture of BP, causative molecular pathways perturbing BP regulation, and pharmacogenomics can help with the selection of precision and personalized medicine, as well as improve morbidity and mortality in adulthood. [ABSTRACT FROM AUTHOR]

In the initial diagnostics of arterial hypertension (AH) laboratory medicine is a cornerstone, along with a blood pressure (BP) measurement and an electrocardiogram. It mainly refers to routine blood and urine tests for diagnosis and monitoring primary hypertension and its associated conditions such as asymptomatic hypertension-mediated organ damage, chronic kidney disease and hypertensive disorders of pregnancy. In addition, long term non-fatal and fatal risks for cardiovascular (CV) events in hypertension are assessed based on clinical and laboratory data. Furthermore, laboratory medicine is involved in the management of hypertension, especially in monitoring the disease progression. However, antihypertensive drugs may interfere with laboratory test results. Diuretics, especially thiazides, can affect blood and urine sodium concentrations, or angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can affect the blood biomarkers of the renin-angiotensin-aldosterone system (RAAS). It's dysfunction plays a critical role in primary aldosteronism (PA), the most common endocrine disorder in secondary hypertension, which accounts for only small proportion of AH in relative terms but substantial proportion of hypertensives in absolute terms, affecting younger population and carrying a higher risk of CV mortality and morbidity. When screening for PA, aldosterone-to-renin ratio still contributes massively to the increased incidence of the disease, despite certain limits. In conclusion, laboratory medicine is involved in the screening, diagnosis, monitoring and prognosis of hypertension. It is of great importance to understand the preanalytical and analytical factors influencing final laboratory result. [ABSTRACT FROM AUTHOR]

Natural bioactive compounds, like β-carotene (βC), are widely recommended as pharmaceutical supplements that are meant to aid in the treatment of diseases such as cardiovascular diseases. However, extreme hydrophobic nature, chemical instability, and low bioavailability of βC limit its clinical application. The purpose of this study was to synthesize and characterize silica nanoparticles (SiNPs) and βC-loaded silica nanoparticles (βC-SiNPs), and then study its activity as an antihypertensive agent in an experimental animal model. The sol–gel method was utilized in the preparation of SiNPs using different solvent systems. The loading of βC was accomplished through an in situ-loading method. The physicochemical characterization of obtained SiNPs was carried out to obtain information about morphology, average particle size, chemical integrity, thermal properties, and colloidal stability. In addition, the encapsulation efficiency (EE%) and release profile in either simulated gastric fluid or in physiological conditions were also investigated. The antihypertensive activity was evaluated in NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rat model. The results showed that the sol–gel synthesis SiNPs exhibited a spherical shape nanoparticle with an average size of 122 ± 38 nm for methanol/water mixture and 598 ± 123 nm for ethanol/water mixture. However, the sample with 0.05 g βC content revealed less average particle size (103 ± 22 nm) with a high EE% of 86%. The encapsulation efficiency (EE %) ranged from 36.4 to 86.8% according to the loading method and βC content. In addition, the drug release studies showed two distinct release steps due to initial burst effect followed by a controlled release. Indeed, the lowest dose of (βC-SiNPs) exhibited ameliorative effects against L-NAME-induced hypertension in adult male Wistar rats. Heart tissues and blood were obtained after rats were administered L-NAME and/or βC-SiNPs orally for 2 weeks for additional histological and biochemical studies. The results revealed that L-NAME therapy resulted in significant cardiac pathological damage as well as a rise in heart function analyses as serum LDH and creatine kinase (CK-MB). In conclusion, nanostructured vehicles (i.e., silica NPs) could be a promising strategy for controlling release of hydrophobic bioactive compounds in pharmaceutical industry and act as antihypertensive agent by restoring biochemical parameters and the histopathological changes in cardiac muscles. [ABSTRACT FROM AUTHOR]

ObjectiveBlood pressure (BP) control rates among adult patients taking antihypertensive medications in the United States have not improved over the last decade. Many CKD adults require more than one class of antihypertensive agent to reach the BP target recommended by the guidelines. However, no study has quantified the proportion of adult CKD patients taking antihypertensive medication who are on monotherapy or combination therapy.MethodsNational Health and Nutrition Examination Survey data during 2001-2018 was used, including adults with CKD taking antihypertensive medication (age ≥ 20 years, n = 4,453). BP control rates were investigated under the BP targets recommended by the 2021 KDIGO, the 2012 KDIGO, and the 2017 ACC/AHA guidelines.ResultsThe percentages of uncontrolled BP among US adults with CKD taking antihypertensive medication were 81.4% in 2001-2006 and 78.2% in 2013-2018. The proportion of monotherapy of antihypertensive regimen were 38.6, 33.3, and 34.6% from 2001 to 2006, 2007-2012, and 2013-2018, with no obvious difference. Similarly, there was no significant change in percentages of dual-therapy, triple-therapy, and quadruple-therapy. Although proportion of CKD adults not treated with ACEi/ARB decreased from 43.5% in 2001-2006 to 32.7% in 2013-2018, treatment of ACEi/ARB among patients with ACR > 300 mg/g had no significant change.ConclusionThe BP control rates among US adult CKD patients taking antihypertensive medications have not improved from 2001 to 2018. Mono-therapy accounted for about one third of adult CKD patients taking antihypertensive medication and not changed. Increasing antihypertensive medication combination therapy may help improve BP control in CKD adults in the United States.

We investigated the effect of dietary inclusions of Moringa seed (5% and 10%) on blood pressure, angiotensin-1 converting enzyme (ACE) activity, and gene expression, as well as redox status in hypertensive rats. Wistar strain albino rats were fed moringa seed-based diets for two weeks prior L-NAME (40 mg/kg/day, p.o.) administration for another ten days. Subsequently, the blood pressure was monitored. Furthermore, the kidney homogenates were assayed for ACE activity and gene expression, as well as oxidative stress markers. The increased (systolic = 297 ± 59.30 mmHg; diastolic= 242 ± 51.96 mmHg) blood pressure, arginase activity, and reduced nitric oxide level were significantly ameliorated in hypertensive rats treated with the seed. However, the elevated ACE activity was significantly reduced but not the upregulated ACE1 gene. Also, the reduced antioxidant enzyme activities were ameliorated with a significant downregulation in their regulator-Nrf2. Rutin (4.07 ± 0.02 mg/g) and quercitrin (4.06 ± 0.01 mg/g), among others, were found in the seed. This study suggests that moringa seed offers its antihypertensive properties by acting as an ACE inhibitor but not its gene modulator, and also modulates the antioxidant system through interaction with Nrf2. Moringa seed could act as an ACE inhibitor and not its gene modulator. [ABSTRACT FROM AUTHOR]

Background: Frailty and hypertension are interrelated, but it remains unclear whether this relationship is modified by antihypertensive drugs. Methods and results: A systematic review of PubMed and Web of Science databases was performed to review the influence of hypertension management on preventing the occurrence or progression of frailty in older people aged 65 and over. Studies providing information on this association regardless of the study setting, or definition of hypertension and frailty were included. Among the initial 2298 articles identified, 7 were included in the review. Three observational studies assessed the association between frailty and hypertension. Two of them reported no relationship between Aldosterone Antagonists use and frailty prevention. No relationship between BP and incidence frailty after adjustment for hypertension treatment was observed in two other articles. An indirect relationship was reported in the RCTs included. Higher AT11RaAb levels (control group), can lead to a generalized weakness/frailty risk shown by a decrease in grip strength (r = –0.57, p < 0.005) and walking speed (r = – 0.47, p < 0.005). No significant differences between int-hypertensive intervention and control were observed in frailty status after a 12-weeks follow-up after applying three different frailty measurement tools in the other RCT. Conclusions: Based on the results of this systematic review we conclude that BP and frailty occur together but whether the treatment with anti-hypertensive drugs modifies this relationship remains unclear and needs to be further investigated. [ABSTRACT FROM AUTHOR]

Background and purpose: Hypertension is a risk factor for subarachnoid hemorrhage and is also considered a risk factor for saccular intracranial aneurysm (sIA) formation. However, there is little direct evidence that antihypertensive medication will reduce sIA formation. Methods: The impact of antihypertensive medication on de novo sIA formation was studied in an angiographically followed cohort of 1419 patients. Patients were identified from our population‐based Kuopio Intracranial Aneurysm Database, and data on the purchases of antihypertensive medication were obtained from a national registry. Univariate and multivariate analyses were used to investigate the risk factors. Results: Of the 966 sIA patients who were prescribed with antihypertensive medication, 841 patients used the medication regularly; 20 of them had de novo sIA. One hundred and twenty‐five patients used the medication irregularly and 12 of them developed de novo sIAs. Four hundred and fifty‐three patients did not use antihypertensive medication even though 27 of them had a diagnosis of hypertension, and 10 of them developed de novo sIAs. In the multivariate analysis antihypertensive medication did not significantly reduce de novo sIA formation (hazard ratio [HR] 1.60, 95% confidence interval [CI] 0.84–3.06). Age at primary diagnosis (HR: 0.95, 95%: CI 0.93–0.98) and smoking history (HR: 5.53, 95% CI: 2.77–11.05) were significant risk factors for de novo sIA formation. Also, irregular usage of antihypertensive medication was a significant risk factor (HR: 3.84, 95% CI: 1.59–9.29) for de novo sIA formation. Conclusions: Antihypertensive agents were not associated with a reduction of de novo sIA formation, but irregular use of antihypertensive agents was associated with an increased risk of de novo sIA formation. [ABSTRACT FROM AUTHOR]

Abstract Purpose Colorectal cancer (CRC) diagnosis is associated with high mortality in the United States and thus warrants the study of novel treatment approaches. Vascular changes are well observed in cancers and evidence indicates that antihypertensive (AH) medications may interfere with both tumor vasculature and in recruiting immune cells to the tumor microenvironment based on preclinical models. Extant literature also shows that AH medications are correlated with improved survival in some forms of cancer. Thus, this study sought to explore the impact of AH therapies on CRC outcomes. Patients and Methods This study was a non‐interventional, retrospective analysis of patients aged 65 years and older with CRC diagnosed from January 1, 2007 to December 31st, 2012 in the Surveillance, Epidemiology, and End‐Results (SEER)‐Medicare database. The association between AH drug utilization on AJCC stage I–III CRC mortality rates in patients who underwent treatment for cancer was examined using Cox proportional hazards models. Results The study cohort consisted of 13,982 patients diagnosed with CRC. Adjusted Cox proportional hazards regression showed that among these patients, the use of AH drug was associated with decreased cancer‐specific mortality (HR: 0.79, 95% CI: 0.75–0.83). Specifically, ACE inhibitors (hazard ratio [HR]: 0.84, 95% CI: 0.80–0.87), beta‐blockers (HR: 0.87, 95% CI: 0.84–0.91), and thiazide diuretics (HR: 0.83, 95% CI: 0.80–0.87) were found to be associated with decreased mortality. An association was also found between adherence to AH therapy and decreased cancer‐specific mortality (HR: 0.94, 95% CI: 0.90–0.98). Conclusion Further research needs to be performed, but AH medications may present a promising, low‐cost pathway to supporting CRC treatment for stage I–III cancers.

Background: Azilsartan is an angiotensin II receptor blocker indicated for the treatment of adult hypertension. A previous single-dose study suggested that azilsartan may also be a promising agent for paediatric hypertension. However, the long-term safety and efficacy of azilsartan in children have not been established. Methods: We conducted a phase 3, single-arm, open-label, prospective study to evaluate the safety and efficacy of azilsartan in pediatric patients with hypertension. Twenty-seven patients aged 6–15 years were treated with once-daily azilsartan for 52 weeks. The starting dose was 2.5 mg for patients weighing < 50 kg (N = 22) and 5 mg for patients weighing ≥ 50 kg (N = 5), with doses titrated up to a maximum of 20 and 40 mg, respectively. Results: Azilsartan showed acceptable tolerability at doses up to 20 mg in patients weighing < 50 kg and 40 mg in those weighing ≥ 50 kg. Most drug-related adverse events (AEs) were mild, with one patient (3.7%) experiencing a severe and serious drug-related AE (acute kidney injury). One patient (3.7%) had a mild increase in serum creatinine level, which resolved after treatment discontinuation. The blood pressure-lowering effect of azilsartan was observed as early as Week 2. Overall, approximately half of the patients achieved their target blood pressure at the end of azilsartan treatment. Conclusions: Our study suggests that azilsartan has an acceptable safety profile in hypertensive patients aged 6–15 years. Azilsartan may be a promising agent for treating paediatric hypertension. [ABSTRACT FROM AUTHOR]

ImportanceAlthough patients with acute stroke are routinely evaluated for potential treatment (ie, treatability of the stroke), preventability of the presenting stroke is generally not seriously considered.ObjectiveTo systematically analyze stroke preventability.Design, setting, and participantsWe evaluated medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012, at the University of California Irvine Medical Center. Mean (SE) patient age was 67.2 (0.8) years. Data analysis was conducted from July 3, 2014, to August 4, 2015.ExposuresMedical records were systematically examined for demographic information, stroke risk factors, stroke severity, and acute stroke treatment.Main outcomes and measuresWe defined stroke preventability as the degree to which the patient's presenting stroke was preventable. Using variables easily determined at onset of stroke, we developed a 10-point scale (0, not preventable; 10, most preventable) to classify the degree of stroke preventability. Our focus was effectiveness of treatment of hypertension (0-2 points), hyperlipidemia (0-2 points), and atrial fibrillation (0-4 points), as well as use of antithrombotic treatment for known prior cerebrovascular and cardiovascular disease (0-2 points).ResultsTotal risk scores ranged from 0 to 8 (mean [SE], 2.2 [0.1]), with 207 patients (75.5%) exhibiting some degree of preventability (score of 1 or higher). Seventy-one patients (25.9%) had scores of 4 or higher, indicating that the stroke was highly preventable. Severity of stroke as determined by the National Institutes of Health Stroke Scale score was not related to preventability of stroke. However, 21 of 71 patients (29.6%) whose stroke was highly preventable were treated with intravenous or intra-arterial acute stroke therapy while these treatments were provided for only 13 of 67 patients (19.4%) with scores of 0 (no preventability) and 19 of 136 patients (14.0%) with scores of 1 to 3 (low preventability) (P = .03).Conclusions and relevanceMost patients with acute stroke exhibited some degree of preventability. Preventability and treatment of stroke were significantly associated, indicating that the most preventable strokes paradoxically were more likely to receive acute treatment.

Background: Resistant hypertension is defined when the blood pressure remains elevated above the therapeutic target levels despite the use of three antihypertensive agents including calcium channel blocker (CCB), renin-angiotensin system (RAS) blocker and a diuretic. These drugs should be used at maximally tolerated doses and white coat effect and non-adherence should also be excluded. In this article, by describing a case of resistant hypertension, we discuss a diagnostic and therapeutic approach to resistant hypertension. Case Presentation: A 59 years old man, known case of diabetic nephropathy with a serum creatinine level of 1.2 mg/dL and proteinuria of about 3300 mg in 24 hours referred to Hypertension Clinic of Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, for evaluation of resistant hypertension. The patient was under treatment by losar-H, diltiazem, and furosemide, which are not appropriate combinations of antihypertensive agents. The ambulatory blood pressure monitoring (ABPM) of the patient revealed daytime and nighttime hypertension and also the non-dipping status of blood pressure. Dihydropyridine CCB was prescribed in combination with RAS blocker (Exforge 50 mg/ 160 mg) and the diuretic was changed to thiazide-like agents. In the next step, spironolactone and carvedilol were added for better control of blood pressure. The patient referred to the sleep clinic for polysomnography and evaluation of obstructive sleep apnea. Following three months prescription of these medications, ABPM revealed relatively appropriate control of blood pressure, so the average 24-hour blood pressure decreased from 157/91 mm Hg to 136/83 mm Hg. Conclusion: The complications and mortality of hypertension would be increased dramatically in patients with resistant hypertension. So, an appropriate diagnostic and therapeutic approaches should be considered for these patients. Choosing appropriate diuretic agents would be important in the management of resistant hypertension.

Purpose: Colorectal cancer (CRC) diagnosis is associated with high mortality in the United States and thus warrants the study of novel treatment approaches. Vascular changes are well observed in cancers and evidence indicates that antihypertensive (AH) medications may interfere with both tumor vasculature and in recruiting immune cells to the tumor microenvironment based on preclinical models. Extant literature also shows that AH medications are correlated with improved survival in some forms of cancer. Thus, this study sought to explore the impact of AH therapies on CRC outcomes. Patients and Methods: This study was a non‐interventional, retrospective analysis of patients aged 65 years and older with CRC diagnosed from January 1, 2007 to December 31st, 2012 in the Surveillance, Epidemiology, and End‐Results (SEER)‐Medicare database. The association between AH drug utilization on AJCC stage I–III CRC mortality rates in patients who underwent treatment for cancer was examined using Cox proportional hazards models. Results: The study cohort consisted of 13,982 patients diagnosed with CRC. Adjusted Cox proportional hazards regression showed that among these patients, the use of AH drug was associated with decreased cancer‐specific mortality (HR: 0.79, 95% CI: 0.75–0.83). Specifically, ACE inhibitors (hazard ratio [HR]: 0.84, 95% CI: 0.80–0.87), beta‐blockers (HR: 0.87, 95% CI: 0.84–0.91), and thiazide diuretics (HR: 0.83, 95% CI: 0.80–0.87) were found to be associated with decreased mortality. An association was also found between adherence to AH therapy and decreased cancer‐specific mortality (HR: 0.94, 95% CI: 0.90–0.98). Conclusion: Further research needs to be performed, but AH medications may present a promising, low‐cost pathway to supporting CRC treatment for stage I–III cancers. [ABSTRACT FROM AUTHOR]

Abstract Background The use of cardiovascular medication for the primary prevention of cardiovascular disease (CVD) is potentially inappropriate when potential risks outweigh the potential benefits. It is unknown whether deprescribing preventive cardiovascular medication in patients without a strict indication for such medication is safe and cost-effective in general practice. Methods In this pragmatic cluster randomised controlled non-inferiority trial, we recruited 46 general practices in the Netherlands. Patients aged 40–70 years who were using antihypertensive and/or lipid-lowering drugs without CVD and with low risk of future CVD were followed for 2 years. The intervention was an attempt to deprescribe preventive cardiovascular medication. The primary outcome was the difference in the increase in predicted (10-year) CVD risk in the per-protocol (PP) population with a non-inferiority margin of 2.5 percentage points. An economic evaluation was performed in the intention-to-treat (ITT) population. We used multilevel (generalised) linear regression with multiple imputation of missing data. Results Of 1067 participants recruited between 7 November 2012 and 18 February 2014, 72% were female. Overall, their mean age was 55 years and their mean predicted CVD risk at baseline was 5%. Of 492 participants in the ITT intervention group, 319 (65%) quit the medication (PP intervention group); 135 (27%) of those participants were still not taking medication after 2 years. The predicted CVD risk increased by 2.0 percentage points in the PP intervention group compared to 1.9 percentage points in the usual care group. The difference of 0.1 (95% CI -0.3 to 0.6) fell within the non-inferiority margin. After 2 years, compared to the usual care group, for the PP intervention group, systolic blood pressure was 6 mmHg higher, diastolic blood pressure was 4 mmHg higher and total cholesterol and low-density lipoprotein-cholesterol levels were both 7 mg/dl higher (all P

Background: Resistant hypertension is defined when the blood pressure remains elevated above the therapeutic target levels despite the use of three antihypertensive agents including calcium channel blocker (CCB), renin-angiotensin system (RAS) blocker and a diuretic. These drugs should be used at maximally tolerated doses and white coat effect and non-adherence should also be excluded. In this article, by describing a case of resistant hypertension, we discuss a diagnostic and therapeutic approach to resistant hypertension. Case Presentation: A 59 years old man, known case of diabetic nephropathy with a serum creatinine level of 1.2 mg/dL and proteinuria of about 3300 mg in 24 hours referred to Hypertension Clinic of Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, for evaluation of resistant hypertension. The patient was under treatment by losar-H, diltiazem, and furosemide, which are not appropriate combinations of antihypertensive agents. The ambulatory blood pressure monitoring (ABPM) of the patient revealed daytime and nighttime hypertension and also the nondipping status of blood pressure. Dihydropyridine CCB was prescribed in combination with RAS blocker (Exforge 50 mg/ 160 mg) and the diuretic was changed to thiazidelike agents. In the next step, spironolactone and carvedilol were added for better control of blood pressure. The patient referred to the sleep clinic for polysomnography and evaluation of obstructive sleep apnea. Following three months prescription of these medications, ABPM revealed relatively appropriate control of blood pressure, so the average 24-hour blood pressure decreased from 157/91 mm Hg to 136/83 mm Hg. Conclusion: The complications and mortality of hypertension would be increased dramatically in patients with resistant hypertension. So, an appropriate diagnostic and therapeutic approaches should be considered for these patients. Choosing appropriate diuretic agents would be important in the management of resistant hypertension. [ABSTRACT FROM AUTHOR]

Background: Evidence is increasing that pathways of antihypertensives may have a role in the pathogenesis of depression. However, how the class of antihypertensives affects depression risk remains unclear.Methods: The effects of different classes of antihypertensives on depression were explored using an insurance database in Beijing, China. Antihypertensives in our study included calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), and diuretics (DIUs). Those initially treated with only one class of antihypertensives were included. Stratified analysis was conducted for demographic characteristics, comorbidities, and statin prescriptions.Results: In total, 181,709 newly detected hypertension patients were included. The median follow-up period was 4.33 years and 19,030 participants were with depression by the end. After adjusting for covariates, the incidence density (95% confidence interval, CI) of depression in the BB, ACEI, DIU, CCB, and ARB groups was 3.16 (2.98-3.33), 3.10 (2.91-3.29), 2.70 (2.45-2.94), 2.67 (2.53-2.81), and 2.30 (2.16-2.43) per 100 person-years, respectively. Compared with ARB group, the hazard ratio (95% CI) of depression for BB, ACEI, DIU, and CCB group was 1.37 (1.32-1.43), 1.35 (1.28-1.42), 1.17 (1.08-1.27), and 1.16 (1.12-1.21), respectively. Stratified analysis suggested the highest depression ID remained within the BB or ACEI group.Limitations: Detailed clinical information was unavailable, which may introduce bias. Patients on monotherapy as initial treatment were included and caution is needed for extrapolation.Conclusions: Compared with ARBs, there may be a class effect of other antihypertensives on the risk of depression. [ABSTRACT FROM AUTHOR]

Background Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. Methods and Results Four hundred seventy‐seven patients with mild‐to‐moderate Alzheimer disease were randomized to the calcium‐channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop ≥20/≥10 mm Hg after 1 minute of standing) and OH‐related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow‐up visits. Mean age of the study population was 72.2±8.2 years and mean Mini‐Mental State Examination score was 20.4±3.8. Baseline blood pressure was 137.8±14.0/77.0±8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by −7.8/−3.9 mm Hg for nilvadipine and by −0.4/−0.8 mm Hg for placebo (P

Background Hypertension is a known risk factor for heart failure (HF), possibly via the mechanism of cardiac remodeling and left ventricular hypertrophy (LVH). We studied the extent to which blood pressure (BP) change and evolving LVH contribute to the effect that lisinopril, doxazosin, and amlodipine have on HF compared with chlorthalidone. Methods and Results We conducted causal mediation analysis of ALLHAT (Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial) data (1994‐2002; in‐trial follow‐up). ALLHAT participants with available serial ECGs and BP measurements were included (n=29 892; mean age 67±4 years; 32% black; 56% men): 11 008 were randomized to chlorthalidone, 5967 to doxazosin, 6593 to amlodipine, and 6324 to lisinopril. Evolving ECG LVH and BP lowering served as mediators. Incident symptomatic HF was the primary outcome. Linear regression (for mediator) and logistic regression (for outcome) models were adjusted for mediator‐outcome confounders (demographic and clinical characteristics known to be associated both with both LVH/hypertension and HF). A large majority of participants (96%) had ECG LVH status unchanged, but 4% developed evolving ECG LVH. On average, BP decreased by 11/7 mm Hg. In adjusted Cox regression analyses, progressing ECG LVH (hazard ratio [HR] 1.78 [95% CI 1.43‐2.22]), resolving ECG LVH (HR 1.33 [95% CI 1.03‐1.70]), and baseline ECG LVH (1.17 [95% CI 1.04‐1.31]) carried risk of incident HF. After full adjustment, evolving ECG LVH mediated 4% of the effect of doxazosin on HF. Systolic BP lowering mediated 12% of the effect of doxazosin, and diastolic BP lowering mediated 10% of the effect of doxazosin, 7% of the effect of amlodipine, and borderline 9% of the effect of lisinopril on HF. Conclusions Evolving ECG LVH and BP change account for 4% to 13% of the mechanism by which antihypertensive medications prevent HF. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

Background We have demonstrated that the antihypertensive effect of the angiotensin‐converting enzyme inhibitor, captopril (CAP), is associated with beneficial effects on gut pathology. Coupled with the evidence that CAP exerts prolonged reduction in blood pressure (BP) after discontinuation of treatment, we investigate whether persistent beneficial actions of CAP are linked to alterations of gut microbiota and improvement of hypertension‐induced gut pathology. Methods and Results Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats were treated with CAP (250 mg/kg/day) for 4 weeks followed by withdrawal for 16 weeks. Gut microbiota, gut pathology, BP, and brain neuronal activity were assessed. CAP resulted in a ≈60 mm Hg decrease in systolic BP after 3 weeks of treatment in SHR, and the decrease remained significant at least 5 weeks after CAP withdrawal. In contrast, CAP caused modest decrease in systolic BP in Wistar Kyoto. 16S rRNA gene‐sequencing–based gut microbial analyses in SHR showed sustained alteration of gut microbiota and increase in Allobaculum after CAP withdrawal. Phylogenetic investigation of communities by reconstruction of unobserved states analysis revealed significant increase in bacterial sporulation upon CAP treatment in SHR. These were associated with persistent improvement in gut pathology and permeability. Furthermore, manganese‐enhanced magnetic resonance imaging showed significantly decreased neuronal activity in the posterior pituitary of SHR 4 weeks after withdrawal. Conclusions Decreased BP, altered gut microbiota, improved gut pathology and permeability, and dampened posterior pituitary neuronal activity were maintained after CAP withdrawal in the SHR. They suggest that CAP influences the brain‐gut axis to maintain the sustained antihypertensive effect of CAP after withdrawal.

Currently, only the general control of the risk factors is known to prevent lacunar cerebral infarction, but it is unknown which type of medication for controlling the risk factors has a causal relationship with reducing the risk of lacunar infarction. To unlock this medical mystery, drug-target Mendelian randomization analysis was applied to estimate the effect of common antihypertensive agents, hypolipidemic agents, and hypoglycemic agents on lacunar stroke. Lacunar stroke data for the transethnic analysis were derived from meta-analyses comprising 7338 cases and 254,798 controls. We have confirmed that genetic variants mimicking calcium channel blockers were found to most stably prevent lacunar stroke. The genetic variants at or near HMGCR , NPC1L1 , and APOC3 were predicted to decrease lacunar stroke incidence in drug-target MR analysis. These variants mimic the effects of statins, ezetimibe, and antisense anti- apoC3 agents, respectively. Genetically proxied GLP1R agonism had a marginal effect on lacunar stroke, while a genetically proxied improvement in overall glycemic control was associated with reduced lacunar stroke risk. Here, we show that certain categories of drugs currently used in clinical practice can more effectively reduce the risk of stroke. Repurposing several drugs with well-established safety and low costs for lacunar stroke prevention should be given high priority when doctors are making decisions in clinical practice. This may contribute to healthier brain aging.

Aims: Microballoons are floating particulate system comprising of a hollow core, drug being loaded within the polymeric layer. The aim of the study was to prepare microballoons containing extract of Clerodendrum colebrokianum, as bioactive agent. Methods: The microballoons were prepared by solvent diffusion technique, prepared microballoons were physico-chemically characterized (Scanning Electron Microscopy (SEM), buoyancy determination, entrapment efficiency, etc), in vitro drug release study and estimated for its in vivo antihypertensive activity by 2K1C hypertension induction method. Results: SEM confirmed the microballoons to be spherical with porous surfaces and hollow core. The developed formulation showed a buoyancy varying from 70.18%-89.90%. The entrapment efficiency of bioactives in microballoons was found between 52%-69% with a delayed release of maximum 28% in 8 hr as found from in vitro drug release study. In vivo antihypertensive studies carried out in rat model showed C. colebrookianum extract have good antihypertensive activity in both high and low dose with respect to standard propanolol. The formulations containing both doses were further found to be effectual in the treatment of hypertension because of its floating nature. Conclusion: The results suggested that optimized formulation show an effective extended release of Clerodendrum colebrokianum extract for the treatment of hypertension. [ABSTRACT FROM AUTHOR]

Background: Although left ventricular hypertrophy (LVH) has been established as a predictor of cardiovascular events in chronic kidney disease (CKD), the relationship between the prevalence of LVH and CKD stage during the pre-dialysis period has not been fully examined.Methods: We measured left ventricular mass index (LVMI) in a cross-sectional cohort of participants in the Chronic Kidney Disease Japan Cohort (CKD-JAC) study to identify factors that are associated with increased LVMI in patients with stage 3-5 CKD.Results: We analyzed the baseline characteristics in 1088 participants (male 63.8%, female 36.2%). Diabetes mellitus was the underlying disease in 41.7% of the patients, and mean age was 61.8 ± 11.1 years. LVH was detected in 23.4% of the patients at baseline. By multivariate logistic analysis, independent risk factors for LVH were past history of cardiovascular disease [odds ratio (OR) 2.364; 95% confidence interval ([CI) 1.463-3.822; P = 0.0004], body mass index (OR 1.108; 95% CI 1.046-1.173; P = 0.0005), systolic blood pressure (OR 1.173; 95% CI 1.005-1.369; P = 0.0433), urinary albumin (OR 1.425; 95% CI 1.028-1.974; P = 0.0333), and serum total cholesterol level (OR 0.994; 95% CI 0.989-0.999; P = 0.0174).Conclusion: The cross-sectional baseline data from the CKD-JAC study shed light on the association between LVH and risk factors in patients with decreased renal function. Further longitudinal analyses of the CKD-JAC cohort are needed to evaluate the prognostic value of LVH in CKD patients. [ABSTRACT FROM AUTHOR]

Background: Hypertension is considered as a major health problem in Indonesia, especially in older adult population because of its prevalence increases by age. Treatment strategy and control management of hypertension in Public Health Center (Pusat Kesehatan Masyarakat, Puskesmas) as primary health care should be enhanced to overcome this issue. This study aimed to describe the pattern of antihypertensive agent in older adults. Methods: This was a descriptive study with total sampling method for data collection. Data were collected from medical record of older adult patients with diagnosis of hypertension at Puskesmas Tanjung Sari from January to December 2013. The variables observed were gender, number of visits, the degree of hypertension, types of antihypertensive drug, combinations of antihypertensive drugs, and blood pressure control. Results: The number of older adults with hypertension was 180 people. Some of which, 120 women (66.7%) participated, 152 (84.4%) had hypertension stage 2, 100 (55.6%) had just one visit, and 80 (44.4%) had more than one visit. Among 80 participants with more than one visit, 8 had achieved target blood pressure. There were 166 participants (92.2%) who received single antihypertensive agent (captopril was given the most), and 14 participants (7.8%) who received the combination of two antihypertensive agent (combination of captopril and HCT (hydrochlorothiazide)) were given the most). Conclusions: More than 75% of older adult with hypertension have stage 2 hypertension and are treated by single antihypertensive agent. Ninety percent of the patient have uncontrolled blood pressure.

Background It is not clear whether the effects of lipid‐lowering or antihypertensive medications are influenced by adherence to healthy lifestyle factors. We assessed the effects of both drug interventions in subgroups by the number of healthy lifestyle factors in participants in the HOPE‐3 (Heart Outcomes Prevention Evaluation) trial. Methods and Results In this primary prevention trial, 4 healthy lifestyle factors (nonsmoking status, physical activity, optimal body weight, and healthy diet) were recorded in 12 521 participants who were at intermediate risk of cardiovascular disease (CVD) and were randomized to rosuvastatin, candesartan/hydrochlorothiazide, their combination, or matched placebos. Median follow‐up was 5.6 years. The outcome was a composite of CVD events. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. Participants with ≥2 healthy lifestyle factors had a lower rate of CVD compared with those with fewer factors (HR: 0.85; 95% CI, 0.73–1.00). Rosuvastatin reduced CVD events in participants with ≥2 healthy lifestyle factors (HR: 0.74; 95% CI, 0.62–0.90) and in participants with

Background: Phyllanthus niruri, in Indonesia, is known as “Meniran” has a long history of use in ethnic or traditional medicine worldwide, mainly as an antihypertensive agent. Objective: The present study was designed to isolate and identify active compounds with angiotensin-converting enzyme (ACE) inhibition activity from P. niruri herb and confirm the mechanism of action, affinity, and domain specificity interactions of the isolated compounds. Materials and Methods: Some fractions of P. niruri methanolic extract were subjected to column chromatography and preparative thin-layer chromatography to get active compounds. Structural elucidation was determined via spectroscopic methods. ACE inhibition activity was measured using hippuryl-L-histidyl-L-leucine as a substrate in vitro assay. Furthermore, confirmation of the mechanism of action, affinity, and domain specificity interaction of the isolated compounds on ACE complex macromolecule (protein database id: 1O86) was performed by in silico molecular docking studies. Results: In this work, four active compounds were isolated from aerial part of P. niruri, including hypophyllantin (50% inhibition concentration [IC50] = 0.180 μg/mL), phyllantin (IC50 = 0.140 μg/mL), methyl gallate (IC50 = 0.015 μg/mL), and quercetin 3-O-β-D-glucopyranosyl-(1'''-6'')-α-rhamnoside (IC50 = 0.086 μg/mL). In silico molecular docking method emphasizes ligand-residue interactions, thereby predicting the inhibitory activity of these compounds. After docking to an ACE complex macromolecule, quercetin 3-O-β-D-glucopyranosyl-(1'''-6'')-α-rhamnoside obtained more interactions than lisinopril. Conclusion: The results were obtained from in silico and in vitro experiments and confirm the potential active compound is an ACE inhibitor and a new antihypertensive agent. Abbreviations Used: P. niruri: Phyllanthus niruri; ACE: Angiotensin-converting enzyme; HHL: Hippuryl-L-histidyl-L-leucine; HA: Hippuric acid; PDB: Protein database; IC50: 50% inhibition concentration; FH: N-hexane fraction; FE: Ethyl acetate fraction; TLC: Thin layer chromatography; UV-VIS: Ultraviolet-visible; NMR: nuclear magnetic resonance; FTIR: Fourier–Transform infrared; MS: Mass spectrometry; HMQC: Heteronuclear Multiple-Quantum Correlation; HMBC: Heteronuclear multiple bond correlation; TADOK: Tugas Akhir Mahasiswa Doktor. [ABSTRACT FROM AUTHOR]

Background: Secondary prevention is inadequate in the first 2 years after stroke but what happens after that is less documented. The aim of this study was to assess the use and the adherence to preventive drugs 3 and 6 years after experiencing a transient ischemic attack (TIA) or an ischemic stroke (IS). Methods: The population study was from the AVC69 cohort (IS or TIA admitted in an emergency or stroke unit in the Rhône area, France, for an IS or a TIA during a 7-month period). Medication use was defined as ≥1 purchase during the studied year and adherence as Continuous Measure of Medication Acquisition ≥0.8 using the French medical insurance health care funding database. Results: The study population consisted of 210 patients at 3 years and 163 patients at 6 years. Medication use at 3 and 6 years was, respectively, 80.9 and 79.8% for antithrombotics, 69.1 and 66.3% for antihypertensives, 60.5 and 55.2% for statins and 48.6 and 46.6% for optimal treatment defined as the treatment achieved by the use of the 3 drugs. Adherence to each class was good at 3 years and tends to decrease at 6 years. Conclusions: More than one patient out of 2 do not use the optimal preventive treatment. [ABSTRACT FROM AUTHOR]

Calcium channel blockers (CCBs) are an established class of drug for the management of hypertension. Observational studies have found that CCB use is associated with a reduction in the risk of developing dementia; however, studies have variably linked the CCBs use with the risk of dementia. This meta-analysis aims to assess whether, in elderly hypertensive patients, the use of CCBs alters the risk of developing dementia. We searched PubMed, Embase and Cochrane from August 2013 to 21st August 2017. Studies were screened on the basis of title and abstract. Quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). The primary outcome was an estimate of the risk of dementia in elderly hypertensive CCBs users. The pooled relative risk (RR) was calculated using a generic inverse variance method. A subgroup analysis was also performed based on CCB class. Statistical analyses were performed using Review Manager Version 5.3. The meta-analysis included ten studies comprising 75,239 patients (53.16% female) with a median age and follow-up duration of 72.24 years and 8.21 years respectively. All of the studies were of high quality. The use of CCBs was associated with a significant reduction in the risk of developing dementia in elderly hypertensive patients (RR 0.70 [95% CI: 0.58–0.85] p  = 0.0003) compared to those not using CCBs. In subgroup analysis we found that the dihydropyridine class was associated with a 44% [RR 0.56 (95% CI: 0.40–0.78) p  = 0.0005] reduction in the dementia risk. The use of CCBs was associated with a significant reduction in the risk of developing dementia in elderly hypertensive patients. [ABSTRACT FROM AUTHOR]