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Background: Hypertension among persons with childbearing potential is on the rise. Maintaining proper blood pressure during pregnancy is vital to prevent maternal and neonatal complications. Yet, limited evidence on the risk-benefit of various antihypertensives presents challenges for informed decision-making during this critical period. This study aimed to examine the utilization patterns of different classes of antihypertensives among persons with pre-existing hypertension before, during, and after pregnancy. Methods: We used MarketScan® Commercial Database 2011−2020 to analyze antihypertensive utilization among pregnant persons aged 12 to 55 identified via a validated algorithm. Pre-existing hypertension was defined as ≥1 inpatient or ≥2 outpatient encounters for hypertension within the 180 days preceding the LMP. Antihypertensive utilization was described during target periods: 0–3 months (0-3M) before pregnancy, 1st/2nd/3rd trimester (T1/2/3), 0-3M, and 4-6M after pregnancy. Results: We identified 1,950,292 pregnancies, of which 20,576 (12,978 live and 7,598 non-live) had pre-existing hypertension. Both groups had similar antihypertensive use (80.1% and 81.0%, respectively) during the 6 months before pregnancy (baseline). For live-birth pregnancies, 13.9% of baseline users discontinued treatment during pregnancy, while 28.9% of non-users initiated antihypertensives during pregnancy, and 17.2% started postpartum. Before pregnancy, the predominant antihypertensives included thiazide diuretics (21.9%), combined α- and β-blockers (18.4%), and dihydropyridines (16.2%). During pregnancy, thiazide diuretics, cardioselective β-blockers, and ACE inhibitors declined (T3: 3.0%, 4.2%, and 0.8%). Dihydropyridine use was steady during pregnancy, but preference shifted from amlodipine to nifedipine in T3 (2.2.% vs.10.8%). Central α2‐agonists increased during pregnancy (up to 15.2% in T3) compared to both pre- (9.8%) and post-pregnancy (5.7%). ARBs mirrored ACE inhibitors, with less than 1% utilization in later trimesters. Combination agents dropped from 10.8% pre-pregnancy to 0.8% in T3, then rebounded to 7.3% post-pregnancy. Conclusion: Research is warranted to evaluate the choice of antihypertensives and optimal timing to switch to safer alternatives, considering maternal and fetal outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Angiotensin receptor blockers are widely used antihypertensive drugs in South Korea. In 2021, the Korea Ministry of Food and Drug Safety acknowledged the need for national compensation for a drug-induced liver injury (DILI) after azilsartan use. However, little is known regarding the association between angiotensin receptor blockers and DILI. Objective: We conducted a retrospective cohort study in incident users of angiotensin receptor blockers from a common data model database (1 January, 2017–31 December, 2021) to compare the risk of DILI among specific angiotensin receptor blockers against valsartan. Methods: Patients were assigned to treatment groups at cohort entry based on prescribed angiotensin receptor blockers. Drug-induced liver injury was operationally defined using the International DILI Expert Working Group criteria. Cox regression analyses were conducted to derive hazard ratios and the inverse probability of treatment weighting method was applied. All analyses were performed using R. Results: In total, 229,881 angiotensin receptor blocker users from 20 university hospitals were included. Crude DILI incidence ranged from 15.6 to 82.8 per 1000 person-years in treatment groups, most were cholestatic and of mild severity. Overall, the risk of DILI was significantly lower in olmesartan users than in valsartan users (hazard ratio: 0.73 [95% confidence interval 0.55–0.96]). In monotherapy patients, the risk was significantly higher in azilsartan users than in valsartan users (hazard ratio: 6.55 [95% confidence interval 5.28–8.12]). Conclusions: We found a significantly higher risk of suspected DILI in patients receiving azilsartan monotherapy compared with valsartan monotherapy. Our findings emphasize the utility of real-world evidence in advancing our understanding of adverse drug reactions in clinical practice. [ABSTRACT FROM AUTHOR]

Prescribing cascade is a significant clinical problem but is often overlooked. We explore the incidence of the prescribing cascades of antigout medications related to thiazide treatment in gout-naïve hypertensive adults newly exposed to the pharmacological treatment. This population-based, retrospective cohort study used the Taiwan National Health Insurance Registry Database. Gout-naïve hypertensive adults who were newly dispensed first-line antihypertensive drugs between January 1, 2000, and December 31, 2016, were enrolled. Patients were divided into the thiazide group (n = 4192) and the non-thiazide group (n = 81,083). The non-thiazide group included patients who received an angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blocker, or beta-blocker. The study utilized propensity score matching and multivariable Cox regression models to investigate the prescribing cascade of antigout agents following antihypertensive treatment, adjusting for factors like age, sex, comorbidities, and concurrent medications. After propensity score matching, each group consisted of 4045 patients, with the thiazide group exhibiting a higher risk of being prescribed antigout medications across different time intervals post-treatment initiation. Specifically, adjusted hazard ratios (aHRs) for the thiazide group were 2.23, 2.07, and 2.41 for < 30 days, 31–180 days, and > 180 days, respectively, indicating a sustained and significant risk over time. Comparative analyses revealed thiazide diuretics were associated with a higher risk of antigout medication prescriptions compared to other antihypertensive classes, particularly evident after 180 days. Subgroup analyses across various demographics and comorbidities consistently showed an increased risk in the thiazide cohort. Gout-naïve hypertensive adults newly dispensed thiazide had a higher risk of subsequently adding antigout agents than those taking other first-line antihypertensive medications. The awareness and interruption of these prescribing cascades are critical to improving patient safety. [ABSTRACT FROM AUTHOR]

Purpose: To examine the association of several antihypertensive medication classes with incidence of Parkinson's disease (PD), taking into account possible underlying conditions. Methods: In a case-control study based on a large primary care database and including 21,981 PD cases and 21,981 non-PD controls matched for age, sex, and possible treatment indications associations with different antihypertensive medication groups, including diuretics, betablockers, calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin-II receptor-blockers and PD were examined. Results: Antihypertensive medications overall were associated with a lower risk of subsequent diagnosis of PD (OR: 0.94, 95% CI 0.90–0.97), with the negative association most significant for medications acting on the renin–angiotensin–aldosterone system. A positive association with diagnosis of PD was only seen for betablockers and restricted to those with relatively young age and not in those with longer treatment duration. Conclusion: When taking into account underlying diagnoses, antihypertensive medications overall were associated with a reduced incidence of PD. [ABSTRACT FROM AUTHOR]

Background: Despite declining mortality in most countries and in Lithuania, ovarian cancer burden has remained high. Studies have indicated that antihypertensive medications use may help to improve ovarian cancer survival, however findings remain controversial. The aim of the study was to analyse the association between post-diagnosis antihypertensive medications intake and cancer-specific survival in ovarian cancer patients. Methods: This retrospective cohort study included 588 ovarian cancer cases diagnosed between 2013 and 2015. Hazard ratios (HR) and corresponding 95% confidence intervals (95%CI) were estimated using multivariable Cox proportional hazards models to assess associations between antihypertensive medications and ovarian cancer-specific mortality. Results: In total, 279 (47%) patients died during the follow-up; 242 (87%) of them died due to ovarian cancer. The risk of ovarian cancer death was reduced in angiotensin-converting enzyme inhibitors (ACE inhibitors) users vs. non-users (HR 0.55, 95% CI: 0.36–0.83). Subgroup analysis showed better ovarian cancer survival in higher dose ACE inhibitors users (HR 0.46, 95% CI: 0.28–0.77, p for trend 0.002); the effect was also stronger in age 51–65 years, stage I–III, surgery or chemotherapy treatment, pre-diagnosis ACE inhibitor users' and pre-diagnosis hypertension subgroups. The risk of cancer-specific death was slightly lower among calcium-channel blocker and angiotensin-receptor blocker users and higher among beta-blocker users as compared to non-users, however chance and confounding could not be ruled out. We found no association between the use of centrally and peripherally acting antiadrenergic agents and diuretics and risk of ovarian cancer-specific mortality. Conclusions: Our findings imply that post-diagnosis use of ACE inhibitors may be associated with reduced ovarian cancer-specific mortality; however, further research is needed for the comprehensive assessment. [ABSTRACT FROM AUTHOR]

Background: The association between antihypertensive medication and schizophrenia has received increasing attention; however, evidence of the impact of antihypertensive medication on subsequent schizophrenia based on large-scale observational studies is limited. We aimed to compare the schizophrenia risk in large claims-based US and Korea cohort of patients with hypertension using angiotensin-converting enzyme (ACE) inhibitors versus those using angiotensin receptor blockers (ARBs) or thiazide diuretics. Methods: Adults aged 18 years who were newly diagnosed with hypertension and received ACE inhibitors, ARBs, or thiazide diuretics as first-line antihypertensive medications were included. The study population was sub-grouped based on age (> 45 years). The comparison groups were matched using a large-scale propensity score (PS)-matching algorithm. The primary endpoint was incidence of schizophrenia. Results: 5,907,522; 2,923,423; and 1,971,549 patients used ACE inhibitors, ARBs, and thiazide diuretics, respectively. After PS matching, the risk of schizophrenia was not significantly different among the groups (ACE inhibitor vs. ARB: summary hazard ratio [HR] 1.15 [95% confidence interval, CI, 0.99–1.33]; ACE inhibitor vs. thiazide diuretics: summary HR 0.91 [95% CI, 0.78–1.07]). In the older subgroup, there was no significant difference between ACE inhibitors and thiazide diuretics (summary HR, 0.91 [95% CI, 0.71–1.16]). The risk for schizophrenia was significantly higher in the ACE inhibitor group than in the ARB group (summary HR, 1.23 [95% CI, 1.05–1.43]). Conclusions: The risk of schizophrenia was not significantly different between the ACE inhibitor vs. ARB and ACE inhibitor vs. thiazide diuretic groups. Further investigations are needed to determine the risk of schizophrenia associated with antihypertensive drugs, especially in people aged > 45 years. [ABSTRACT FROM AUTHOR]

Given possible involvement of the central and peripheral angiotensin system in pain processing, we conducted clinical and preclinical studies to test whether pharmacological inhibition of the angiotensin system would prevent diabetic peripheral neuropathy (DPN) accompanying type 2 diabetes mellitus (T2DM). In the preclinical study, the nociceptive sensitivity was determined in leptin-deficient ob/ob mice, a T2DM model. A clinical retrospective cohort study was conducted, using the medical records of T2DM patients receiving antihypertensives at three hospitals for nearly a decade. In the ob/ob mice, daily treatment with perindopril, an angiotensin-converting enzyme inhibitor (ACEI), or telmisartan, an angiotensin receptor blocker (ARB), but not amlodipine, an L-type calcium channel blocker (CaB), significantly inhibited DPN development without affecting the hyperglycemia. In the clinical study, the enrolled 7464 patients were divided into three groups receiving ACEIs, ARBs and the others (non-ACEI, non-ARB antihypertensives). Bonferroni's test indicated significantly later DPN development in the ARB and ACEI groups than the others group. The multivariate Cox proportional analysis detected significant negative association of the prescription of ACEIs or ARBs and β-blockers, but not CaBs or diuretics, with DPN development. Thus, our study suggests that pharmacological inhibition of the angiotensin system is beneficial to prevent DPN accompanying T2DM. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is the leading cause of heart disease in the world, and discontinuation or nonadherence of antihypertensive medication constitutes a significant global health concern. Patients with hypertension have high rates of medication nonadherence. Studies of reasons for nonadherence using traditional surveys are limited, can be expensive, and suffer from response, white-coat, and recall biases. Mining relevant posts by patients on social media is inexpensive and less impacted by the pressures and biases of formal surveys, which may provide direct insights into factors that lead to non-compliance with antihypertensive medication. Methods: This study examined medication ratings posted to WebMD, an online health forum that allows patients to post medication reviews. We used a previously developed natural language processing classifier to extract indications and reasons for changes in angiotensin receptor II blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) treatments. After extraction, ratings were manually annotated and compared with data from the US Food and Drug administration (FDA) Adverse Events Reporting System (FAERS) public database. Results: From a collection of 343,459 WebMD reviews, we automatically extracted 1867 posts mentioning changes in ACEIs or ARBs, and manually reviewed the 300 most recent posts regarding ACEI treatments and the 300 most recent posts regarding ARB treatments. After excluding posts that only mentioned a dose change or were a false-positive mention, 142 posts in the ARBs dataset and 187 posts in the ACEIs dataset remained. The majority of posts (97% ARBs, 91% ACEIs) indicated experiencing an adverse event as the reason for medication change. The most common adverse events reported mapped to the Medical Dictionary for Regulatory Activities were "musculoskeletal and connective tissue disorders" like muscle and joint pain for ARBs, and "respiratory, thoracic, and mediastinal disorders" like cough and shortness of breath for ACEIs. These categories also had the largest differences in percentage points, appearing more frequently on WebMD data than FDA data (p < 0.001). Conclusion: Musculoskeletal and respiratory symptoms were the most commonly reported adverse effects in social media postings associated with drug discontinuation. Managing such symptoms is a potential target of interventions seeking to improve medication persistence. [ABSTRACT FROM AUTHOR]

Hypertension is very common and remains often poorly controlled in patients with chronic kidney disease (CKD). Accurate blood pressure (BP) measurement is the essential first step in the diagnosis and management of hypertension. Dietary sodium restriction is often overlooked, but can improve BP control, especially among patients treated with an agent to block the renin–angiotensin system. In the presence of very high albuminuria, international guidelines consistently and strongly recommend the use of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker as the antihypertensive agent of first choice. Long-acting dihydropyridine calcium channel blockers and diuretics are reasonable second- and third-line therapeutic options. For patients with treatment-resistant hypertension, guidelines recommend the addition of spironolactone to the baseline antihypertensive regimen. However, the associated risk of hyperkalemia restricts the broad utilization of spironolactone in patients with moderate-to-advanced CKD. Evidence from the CLICK (Chlorthalidone in Chronic Kidney Disease) trial indicates that the thiazide-like diuretic chlorthalidone is effective and serves as an alternative therapeutic opportunity for patients with stage 4 CKD and uncontrolled hypertension, including those with treatment-resistant hypertension. Chlorthalidone can also mitigate the risk of hyperkalemia to enable the concomitant use of spironolactone, but this combination requires careful monitoring of BP and kidney function for the prevention of adverse events. Emerging agents, such as the non-steroidal mineralocorticoid receptor antagonist ocedurenone, dual endothelin receptor antagonist aprocitentan and the aldosterone synthase inhibitor baxdrostat offer novel targets and strategies to control BP better. Larger and longer term clinical trials are needed to demonstrate the safety and efficacy of these novel therapies in the future. In this article, we review the current standards of treatment and discuss novel developments in pathophysiology, diagnosis, outcome prediction and management of hypertension in patients with CKD. [ABSTRACT FROM AUTHOR]

Renin-angiotensin system inhibitors (RASi), particularly angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), are commonly used in the treatment of hypertension and are recommended for kidney protection. Uncertainty remains about the effectiveness of RASi being used as first-line antihypertensive therapy on eGFR maintenance compared to its alternatives, especially for those with no or early-stage chronic kidney disease (CKD). We conducted a retrospective cohort study of 19,499 individuals (mean age 64.1, 43.5% males) from primary care in Singapore with 4.5 median follow-up years. The study cohort included newly diagnosed individuals with hypertension (whose eGFR was mainly in CKD stages G1-G2) and initiated on ACEIs, ARBs, beta-blockers (BBs), calcium channel blockers (CCBs) or diuretics (Ds) as first-line antihypertensive monotherapy. We compared the estimated glomerular filtration rate (eGFR) curve before/after the drug initiation over time of patients under different drug classes and analyzed the time to declining to a more advanced stage CKD. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounding factors. Two key findings were observed. First, after initiating antihypertensive drugs, the eGFR almost maintained the same as the baseline in the first follow-up year, compared with dropping 3 mL/min/1.73 m2 per year before drug initiation. Second, ARBs were observed to be slightly inferior to ACEIs (HR = 1.14, 95% CI = (1.04, 1.23)) and other antihypertensive agents (HR = 1.10, 95% CI = (1.01, 1.20)) in delaying eGFR decline to a more advanced CKD stage in the study population. Our results showed that initiating antihypertensive agents can significantly maintain eGFR for those newly diagnosed patients with hypertension. However, RASi may not be superior to other antihypertensive agents in maintaining eGFR levels for non-CKD or early stages CKD patients. [ABSTRACT FROM AUTHOR]

The current review is to describe the definition and prevalence of resistant arterial hypertension (RAH), the difference between refractory hypertension, patient characteristics and major risk factors for RAH, how RAH is diagnosed, prognosis and outcomes for patients. According to the WHO, approximately 1.28 billion adults aged 30–79 worldwide have arterial hypertension, and over 80% of them do not have blood pressure (BP) under control. RAH is defined as above-goal elevated BP despite the concurrent use of 3 or more classes of antihypertensive drugs, commonly including a long-acting calcium channel blocker, an inhibitor of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a thiazide diuretic administered at maximum or maximally tolerated doses and at appropriate dosing frequency. RAH occurs in nearly 1 of 6 hypertensive patients. It often remains unrecognised mainly because patients are not prescribed ≥3 drugs at maximal doses despite uncontrolled BP. RAH distinctly increases the risk of developing coronary artery disease, heart failure, stroke and chronic kidney disease and confers higher rates of major adverse cardiovascular events as well as increased all-cause mortality. Timely diagnosis and treatment of RAH may mitigate the associated risks and improve short and long-term prognosis. Resistant arterial hypertension is a serious condition that leads to severe cardiovascular complications, such as heart attack, stroke and death. It is defined as above-goal elevated blood pressure despite the concurrent use of 3 or more classes of antihypertensive medications administered at maximum or maximally tolerated doses and at appropriate dosing frequency. Non-adherence to antihypertensive medications must be excluded before resistant arterial hypertension is diagnosed. Blood pressure should be measured appropriately. A person should sit in a comfortable chair with back supported, both feet flat on the ground, and legs uncrossed for at least 5 min before blood pressure measurement. A cuff length is supposed to be at least 80% and a width of at least 40% of the arm circumference. Placing the cuff directly on the skin of the upper arm at the level of the heart. Obtaining 3 readings 1 min apart. Discarding the first reading and taking the mean of the second and third readings Resistant arterial hypertension should be distinguished from refractory hypertension, when blood pressure remains uncontrolled on maximal or near-maximal therapy of 5 or more antihypertensive agents of different classes. [ABSTRACT FROM AUTHOR]

This article reviews research on antihypertensive medications including vasodilators, β-blockers, and angiotensin II receptor antagonists that have been approved by the FDA (Food and Drug Administration) since 2011. It covers the discovery of lead compounds, mechanisms of action, structural modifications, structure-activity relationships, and synthesis methods, aiming to serve as a reference for the development of antihypertensive drugs. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggest an association between blood pressure (BP) and functional outcomes in ischemic stroke patients but whether this is causal or due to confounding is uncertain. We used Mendelian randomization (MR) to assess causality, and also explore whether particular classes of anti-hypertensives were associated with a better outcome after ischemic stroke. Methods: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals. The primary outcome was 3-month dependence or death defined as a modified Rankin Scale (mRS) of 3–6. The secondary outcome was disability or death after 90 days defined as mRS 2–6. Cochran's Q statistic in the inverse variance weighted (IVW) model, the weighted median, MR-Egger regression, leave-one-single-nucleotide polymorphism (SNP)-out analysis, MR-Pleiotropy Residual Sum and Outlier methods were adopted as sensitivity analyses. To validate our primary results, we performed independent repeat analyses and Bi-directional MR analyses. Results: Genetic predisposition to higher systolic and diastolic BP was associated with disability or death after ischemic stroke in univariable IVW MR analysis (odds ratio (OR) 1.29, 95% confidence interval (CI): 1.05–1.59, p = 0.014; OR 1.27, 95% CI: 1.07–1.51, p = 0.006, respectively). Pulse pressure was associated with both dependence or death and disability or death after ischemic stroke (OR = 1.05, 95% CI: 1.02–1.08, p = 0.002; OR = 1.04, 95% CI = 1.01–1.07, p = 0.009, respectively). Angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB) were significantly associated with improved functional outcomes (dependence or death, OR 0.76, 95% CI: 0.62–0.94, p = 0.009; OR 0.89, 95% CI: 0.83–0.97, p = 0.005). Proxies for β-blockers, angiotensin receptor blockers (ARB), and thiazides failed to show associations with functional outcomes (p > 0.05). Conclusion: We provide evidence for an association of genetic predisposition to higher BP with a higher risk of 3-month functional dependence after ischemic stroke. Our findings support ACEI and CCB as promising antihypertensive drugs for improving functional outcomes in ischemic stroke. [ABSTRACT FROM AUTHOR]

Background. Hypertension and type 2 diabetes (T2D) are the most prevalent noncommunicable diseases in Mexico and worldwide. According to international practice management guidelines, the principal chronic management therapy is daily oral medication. Aim. We aim to describe the trends of antihypertensive, antidiabetic, and nonsteroidal anti-inflammatory (NSAID) drugs use among the Mexican adult population from 2004–2018. Methods. We analyzed data from the Health Workers Cohort Study (HWCS) for males and females aged >18 years. We calculated the prevalence of chronic diseases and utilization for every kind of antihypertensive, antidiabetic, and NSAIDs (measured by self-reported utilization) at baseline and two follow-ups (2004, 2010, and 2017). Trends were analyzed using Fisher's exact test. Results. Hypertension prevalence increased from 19.8 to 30.3%, higher than T2D prevalence from 7.0 to 12.8% through fourteen years of follow-up. Like the self-reported dual therapy, the proportion of patients using beta-blockers and angiotensin II receptor blockers increased. Regarding T2D, the prevalence of metformin utilization increased to 83.9%. The utilization of common NSAIDs, mainly for muscular pain, remained around 13 to 16%. Conclusions. Our findings showed a changing prevalence of drug utilization for hypertension and T2D between 2004 and 2018 and consistent use of NSAIDs in the adult Mexican population. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify the effect of antihypertensive medication on risks of open-angle glaucoma (OAG) among patients diagnosed with hypertension (HTN). A total of 5,195 patients, who were diagnosed with HTN between January 1, 2006 and December 31, 2015, and subsequently diagnosed with OAG, were selected for analysis. For each OAG patient, 5 non-glaucomatous, hypertensive controls were matched (n = 25,975) in hypertension diagnosis date, residential area, insurance type and economic status. Antihypertensive medications were stratified into 5 types: angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB), β-blockers and diuretics. Relative risks were calculated. After adjusting for age, sex, body mass index, lifestyle, comorbidities, blood pressure (BP), follow-up duration, and use of other types of antihypertensive drugs, ARB and CCB were found to slightly increase OAG risks (RR 1.1087 (95% CI 1.0293–1.1942); 1.0694 (1.0077–1.1349), respectively). Combinations of ARB with diuretics (1.0893 (1.0349–1.1466)) and CCB (1.0548 (1.0122–1.0991)) also increased OAG risks. The risks for OAG were found to increase by antihypertensive medication use, but the effects appeared to be small. Further studies are necessary to identify the associations of increased BP, medication and therapeutic effect with OAG. [ABSTRACT FROM AUTHOR]

Background: Clinical guidelines for hypertension were updated with lower blood pressure targets following new studies in 2015; the real-world impact of these changes on antihypertensive drug use is unknown. We aimed to describe trends in antihypertensive drug utilization from 2004 to 2019 in British Columbia. Methods: We conducted a longitudinal study to describe the annual prevalence and incidence rate of use of 5 antihypertensive drug classes (thiazides, angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor blockers [ARBs], calcium channel blockers and β-blockers) among BC residents aged 30--75 years. We also conducted a cohort study to compare the risk of discontinuation and switch or add-on therapy between incident users of the above drug classes. We used linkable administrative health databases from BC. We performed a Fine--Gray competing risk analysis to estimate subhazard ratios. Results: Among BC residents aged 30--75 years (population: 2 376 282 [2004] to 3 014 273 [2019]), the incidence rate of antihypertensive drug use decreased from 23.7 per 1000 person-years in 2004 to 18.3 per 1000 person-years in 2014, and subsequently increased to 22.6 per 1000 person-years in 2019. The incidence rate of thiazide use decreased from 8.9 per 1000 person-years in 2004 to 3.2 per 1000 person-years in 2019, and incidence rates for the other drug classes increased. Incident users receiving thiazide monotherapy had an increased risk of discontinuing any antihypertensive treatment compared with ACE inhibitor monotherapy (subhazard ratio 0.96, 95% confidence interval [CI] 0.95--0.97), ARB monotherapy (subhazard ratio 0.84, 95% CI 0.81--0.87) and thiazide combination with ACE inhibitor or ARB (subhazard ratio 0.86, 95% CI 0.84--0.88), and had the highest risk of switching or adding on. Interpretation: First-line use of thiazides continued to decrease despite a marked increase in incident antihypertensive therapy following updated guidelines; incident users receiving ARB monotherapy were least likely to discontinue, and incident users receiving thiazide monotherapy were more likely to switch or add on than users of other initial monotherapy or combination. Further research is needed on the factors influencing treatment decisions to understand the differences in trends and patterns of antihypertensive drug use. [ABSTRACT FROM AUTHOR]

This study aims to investigate the association between antihypertensive use and the risk of cataract in a matched case-control study. We analysed the Korean National Health Insurance Service-Health Screening Cohort database from 2002 to 2013. We defined 'cases' as patients prescribed antihypertensives and underwent their first eye cataract surgery between 2010 and 2013. 'Controls' were patients prescribed antihypertensives and no history of cataract surgery or diagnosis between 2002 and 2013. Four controls were matched to each case by several variables. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated for cataract risk using a conditional logistic regression model after adjustment. The analyses comprised 12,166 cases and 48,664 controls. The adjusted ORs for cataracts were 1.18 (95% CI: 1.12–1.24) in thiazide diuretics, 1.12 (95% CI: 1.07–1.18) in beta-blockers, 0.94 (95% CI: 0.90–1.00) in calcium channel blockers, 1.22 (95% CI: 1.14–1.30) in angiotensin-converting enzyme (ACE) inhibitors, and 0.97 (95% CI: 0.91–1.03) in angiotensin II receptor blockers compared to 'non-use' of each antihypertensive. In a nationwide case-control study, the use of thiazide diuretics, beta-blockers, or ACE inhibitors do not represent minimal clinical important difference in the risk of cataract and the use of calcium channel blockers or angiotensin II receptor blockers is not associated with an increased risk of cataracts compared to non-use of each antihypertensive. Given the benefits of treating hypertension, such as the reduction in further complications, we suggest there is no need to change current clinical practice for antihypertensives. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a major public health problem in India, affecting a significant proportion of the population. Drug utilization research is important for assessing the rationality of drug treatment and for identifying areas for improvement. This study examined the drug utilization pattern of antihypertensive drugs in hypertensive patients at an Outpatient Department (OPD) in Udaipur, Rajasthan, India, based on JNC-8 classification. Materials and Methods: The observational cross-sectional study included 300 hypertension patients aged above 25 attending the hypertension clinic. Exclusions were made for inpatients, age < 25, uncertain diagnosis, pregnant/lactating mothers, and patients subsequently admitted after OPD visits. Results: The majority of affected patients were above 60 years old, with most having hypertension for 2-5 years, often accompanied by Type II Diabetes Mellitus. Oral administration was the primary drug delivery route. On average, patients received 1.93 antihypertensive drugs per encounter (range: 1 to 4), with an average of 5.82 drugs per encounter (range: 1 to 12). Losartan (72%) and amlodipine (46%) were the most prescribed drugs, with Angiotensin Receptor Blockers (ARBs) being the most prescribed drug class (79.3%), followed by Calcium Channel Blockers (CCBs) at 46.6%. The most common therapy was a two-drug combination (44.6%), followed by single-drug therapy (33%). Approximately 26.3% of prescriptions indicated potential drug interactions. Conclusions: This study provides valuable baseline data on the prescribing pattern of antihypertensive drugs. Rational prescribing practices are being followed, with the majority of patients being prescribed a combination of two or three antihypertensive drugs. However, there is a need to educate patients about the risks associated with uncontrolled high blood pressure and the benefits of lifestyle changes. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify the effect of antihypertensive medication on risks of open-angle glaucoma (OAG) among patients diagnosed with hypertension (HTN). A total of 5,195 patients, who were diagnosed with HTN between January 1, 2006 and December 31, 2015, and subsequently diagnosed with OAG, were selected for analysis. For each OAG patient, 5 non-glaucomatous, hypertensive controls were matched (n = 25,975) in hypertension diagnosis date, residential area, insurance type and economic status. Antihypertensive medications were stratified into 5 types: angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB), β-blockers and diuretics. Relative risks were calculated. After adjusting for age, sex, body mass index, lifestyle, comorbidities, blood pressure (BP), follow-up duration, and use of other types of antihypertensive drugs, ARB and CCB were found to slightly increase OAG risks (RR 1.1087 (95% CI 1.0293–1.1942); 1.0694 (1.0077–1.1349), respectively). Combinations of ARB with diuretics (1.0893 (1.0349–1.1466)) and CCB (1.0548 (1.0122–1.0991)) also increased OAG risks. The risks for OAG were found to increase by antihypertensive medication use, but the effects appeared to be small. Further studies are necessary to identify the associations of increased BP, medication and therapeutic effect with OAG. [ABSTRACT FROM AUTHOR]

While previous studies have examined the dose-response characteristics of certain antihypertensive drugs alone or in combination, response surface analysis for combination therapies involving angiotensin receptor blockers (ARBs) and either amlodipine (AML) or hydrochlorothiazide (HCT) has not been explored, particularly in the context of lowdose combinations. The objectives of present study were to generate useful dose-response information for the combination of ARB/AML or ARB/HCT and to predict the blood pressure lowering effects of combination therapies compared to monotherapies. We reviewed the New Drug Application data of combination drugs of ARB/AML and ARB/HCT. Data on systolic blood pressure (SBP), from studies conducted using a factorial dose-response design over a period of 8-12 weeks, were used. The placebo-subtracted SBP change was used for analysis. Response surface analyses of the collected data were conducted using a polynomial regression model. For ARB/AML combination, the quadratic polynomial regression model containing two linear terms, two quadratic terms, and one interaction term was best fitted to the naïve pooled data. Meanwhile, for ARB/HCT combination, the best-fitted model was a quadratic model that included two linear terms and two quadratic terms. The 1/2-dose combination of these medications, compared to each monotherapy, resulted in predicted SBP reductions that were 8-30% greater. The ratio of the estimated antihypertensive effects of the combination to the expected additive effects of each component ranged from 82% to 100% of the expected effect. These results can provide a rationale for developing lower-dose combinations of ARB/AML or ARB/HCT and assist in designing clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes and hypertension are two major non-communicable diseases that commonly coexist and increase the risk of cardiovascular and renal complications. Objectives: to evaluate the prescribing pattern of antihypertensive drugs in diabetic patients with hypertension at a tertiary care center. Methods: This was a cross-sectional observational study conducted at a tertiary care center in suryapet over six months. The study included all diabetic patients with hypertension who visited the outpatient department during the study period. The data were collected through patient interviews and medical records. Demographic and clinical data were recorded, including age, gender, duration of diabetes, and blood pressure. The antihypertensive drugs prescribed were recorded, along with the dose and frequency of administration. Results: A total of 250 diabetic patients with hypertension were included in the study. The majority of the patients were male (56%). The mean age was 58.6 years (SD=10.2), and the mean duration of diabetes was 9.8 years (SD=5.2). The most commonly prescribed antihypertensive drugs were angiotensin-converting enzyme inhibitors (ACEIs) (57%), followed by calcium channel blockers (CCBs) (29%) and angiotensin receptor blockers (ARBs) (27%). The most commonly prescribed combination therapy was ACEIs and CCBs (23%). The average number of antihypertensive drugs prescribed per patient was 1.9 (SD=0.7).Conclusion: This study showed that ACEIs were the most commonly prescribed antihypertensive drugs in diabetic patients with hypertension at the tertiary care center. Combination therapy with ACEIs and CCBs was the most commonly prescribed. The findings suggest the need for improved adherence to evidence-based guidelines in the management of hypertension in diabetic patients. [ABSTRACT FROM AUTHOR]

In their recent guidelines, the European Society of Hypertension upgraded β blockers, putting them on equal footing with thiazide diuretics, renin–angiotensin system blockers (eg, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), and calcium channel blockers. The reason offered for upgrading β blockers was the observation that they are often used for many other clinical conditions commonly encountered with hypertension. This upgrade would allow for the treatment of two conditions with a single drug (a so-called twofer). In most current national and international hypertension guidelines, β blockers are only considered to be an alternative when there are specific indications. Compared with the other first-line antihypertensive drug classes, β blockers are significantly less effective in preventing stroke and cardiovascular mortality. To relegate β blockers to an inferiority status as previous guidelines have done was based on the evidence in aggregate, and still stands. No new evidence supports the switch of β blockers back to first-line therapy. We are concerned that this move might lead to widespread harm because of inferior stroke protection. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a major public health problem in India, affecting a significant proportion of the population. Drug utilization research is important for assessing the rationality of drug treatment and for identifying areas for improvement. This study examined the drug utilization pattern of antihypertensive drugs in hypertensive patients at an Outpatient Department (OPD) in Udaipur, Rajasthan, India, based on JNC-8 classification. Materials and Methods: The observational cross-sectional study included 300 hypertension patients aged above 25 attending the hypertension clinic. Exclusions were made for inpatients, age < 25, uncertain diagnosis, pregnant/lactating mothers, and patients subsequently admitted after OPD visits. Results: The majority of affected patients were above 60 years old, with most having hypertension for 2-5 years, often accompanied by Type II Diabetes Mellitus. Oral administration was the primary drug delivery route. On average, patients received 1.93 antihypertensive drugs per encounter (range: 1 to 4), with an average of 5.82 drugs per encounter (range: 1 to 12). Losartan (72%) and amlodipine (46%) were the most prescribed drugs, with Angiotensin Receptor Blockers (ARBs) being the most prescribed drug class (79.3%), followed by Calcium Channel Blockers (CCBs) at 46.6%. The most common therapy was a two-drug combination (44.6%), followed by single-drug therapy (33%). Approximately 26.3% of prescriptions indicated potential drug interactions. Conclusions: This study provides valuable baseline data on the prescribing pattern of antihypertensive drugs. Rational prescribing practices are being followed, with the majority of patients being prescribed a combination of two or three antihypertensive drugs. However, there is a need to educate patients about the risks associated with uncontrolled high blood pressure and the benefits of lifestyle changes. [ABSTRACT FROM AUTHOR]

Background: Most antihypertensives can induce dermal photosensitivity, which may increase melanoma risk. However, corroborating evidence is limited. We examined the associations between use of antihypertensives and melanoma risk.Methods: A nationwide nested case-control study was conducted using data from the Cancer Registry of Norway, the National Registry and the Norwegian Prescription Database in 2004-15. Ten controls were randomly selected for each melanoma case, matched on sex and birth year. The study included 12 048 cases and 117 895 controls. We estimated rate ratios (RRs) with 95% confidence intervals (CIs). All analyses were adjusted for ambient ultraviolet radiation (UVR). We additionally performed active comparator analyses, and sensitivity analyses by only including new users, distinguishing between exclusive and mixed users, allowing for different latency periods, and subgroup analyses by melanoma subtype and clinical stage.Results: Compared with non-use, we observed a slightly increased melanoma risk in users of diuretics (RR 1.08, CI 1.01-1.15), calcium-channel blockers (RR 1.10, CI 1.04-1.18) and drugs affecting the renin-angiotensin system (RR 1.10, CI 1.04-1.16), but not for beta blockers (RR 0.97, CI 0.92-1.03). We found no heterogeneity of associations by melanoma subtype or clinical stage and no dose-response relationship between the cumulative defined daily doses (DDDs) and melanoma. No interaction was found between cumulative DDDs and ambient UVR.Conclusions: Weak associations, with lack of a dose-response relationship and lack of interactions with ambient UVR, in the DDD analysis in this nationwide study do not support a causal relationship between antihypertensives and melanoma risk. [ABSTRACT FROM AUTHOR]

Background: The recent progress in molecular biology generates an increasing interest in investigating molecular biomarkers as markers of response to treatments. The present work is motivated by a study, where the objective was to explore the potential of the molecular biomarkers of renin-angiotensin-aldosterone system (RAAS) to identify the undertaken antihypertensive treatments in the general population. Population-based studies offer an opportunity to assess the effectiveness of treatments in real-world scenarios. However, lack of quality documentation, especially when electronic health record linkage is unavailable, leads to inaccurate reporting and classification bias. Method: We present a machine learning clustering technique to determine the potential of measured RAAS biomarkers for the identification of undertaken treatments in the general population. The biomarkers were simultaneously determined through a novel mass-spectrometry analysis in 800 participants of the Cooperative Health Research In South Tyrol (CHRIS) study with documented antihypertensive treatments. We assessed the agreement, sensitivity and specificity of the resulting clusters against known treatment types. Through the lasso penalized regression, we identified clinical characteristics associated with the biomarkers, accounting for the effects of cluster and treatment classifications. Results: We identified three well-separated clusters: cluster 1 (n = 444) preferentially including individuals not receiving RAAS-targeting drugs; cluster 2 (n = 235) identifying angiotensin type 1 receptor blockers (ARB) users (weighted kappa κw = 74%; sensitivity = 73%; specificity = 83%); and cluster 3 (n = 121) well discriminating angiotensin-converting enzyme inhibitors (ACEi) users (κw = 81%; sensitivity = 55%; specificity = 90%). Individuals in clusters 2 and 3 had higher frequency of diabetes as well as higher fasting glucose and BMI levels. Age, sex and kidney function were strong predictors of the RAAS biomarkers independently of the cluster structure. Conclusions: Unsupervised clustering of angiotensin-based biomarkers is a viable technique to identify individuals on specific antihypertensive treatments, pointing to a potential application of the biomarkers as useful clinical diagnostic tools even outside of a controlled clinical setting. [ABSTRACT FROM AUTHOR]

Angiotensin receptor blockers (ARBs) are commonly prescribed in pediatric hypertension because of the fundamental role of the renin-angiotensin-aldosterone system in the pathogenesis of hypertension. We, therefore, aimed to systematically review articles that investigated efficacy and safety of ARB agents in the pediatric population aged over six years. To do so, the databases of Web of Science, PubMed/MEDLINE, and Scopus were searched to conduct a systematic review by using the following keywords: ("angiotensin receptor blocker" OR "valsartan" OR "losartan") AND ("pediatric" OR "children" OR "child") AND ("high blood pressure" OR "hypertension"). Finally, 12 studies were included in our review, and we found that almost all of them supported the effectiveness and tolerability of different ARB agents. Candesartan cilexetil lowered blood pressure (BP), with a 9 mmHg decline in both systolic and diastolic BP, and proteinuria after four months of treatment. Valsartan and Losartan similarly were shown to be effective in lowering BP in a dose-dependent manner. Headache, dizziness, upper respiratory infection, and cough were the most reported side effects. However, almost all reviewed studies indicated that the safety profile was satisfactory. In conclusion, ARBs are beneficial and well-tolerated antihypertensive medications. [ABSTRACT FROM AUTHOR]

Background: Cardiometabolic disease is a clinical syndrome characterized by multiple metabolic disorders, with atherosclerosis as the core and cardiovascular and cerebrovascular events as the outcome. Drug research and development (R&D) in cardiometabolic diseases has grown rapidly worldwide. However, the development of cardiometabolic drug clinical trials in China remains unclear. This study aims to depict the changing landscape of drug clinical trials for cardiometabolic diseases in China during 2009–2021. Methods: The detailed information of drug trials on cardiometabolic diseases registered in the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform was collected between January 1, 2009, and July 1, 2021. The landscape of cardiometabolic drug clinical trials was analyzed by the characteristics, time trends, indications, pharmacological mechanisms, and geographical distribution. Results: A total of 2466 drug clinical trials on cardiometabolic diseases were extracted and analyzed. The annual number of drug trials increased rapidly in the past twelve years. Among all the trials, the bioequivalence trials (1428; 58.3%) accounted for the largest proportion, followed by phase I (555; 22.5%), phase III (278; 11.3%), phase II (169; 6.9%), and phase IV (26; 1.1%). Of 2466 trials, 2133 (86.5%) trials were monomer drugs, only 236 (9.6%) trials were polypills and 97 (3.9%) were traditional Chinese medicine (TCM) compounds. In terms of pharmacological mechanisms, the number of trials in dihydropyridine (DHP) calcium antagonists 321 (11.9%) ranked first, while trials in angiotensin receptor blocker (ARB) 289 (10.7%) and dipeptidyl peptidase-4 (DPP-4) inhibitor 205 (7.6%) ranked second and third place respectively. Of 236 chemical polypills trials, 23 (9.7%) polypills were the combination of DHP calcium antagonists and statins, while others were the combination of two same pharmacological effect agents. As for the geographical distribution of leading units, 36 trials were led by principal investigators (PI) units from Beijing, followed by Jiangsu (n = 29), Shanghai (n = 19), Guangdong (n = 19), and Hunan (n = 19), showing an uneven regional distribution. Conclusions: Great progress has been made in drug clinical trials on cardiometabolic diseases, especially in antihypertensive agents, hypoglycemic agents, and hypolipidemic agents. However, the insufficient innovation of first-in-class drugs and polypills should be carefully considered by all stakeholders in drug trials. [ABSTRACT FROM AUTHOR]

Introduction: Aortic dissection (AD) is a life-threatening disease. However, the effectiveness of different strategies of antihypertensive therapies in non-operated AD patients is still unclear. Materials and methods: Patients were classified into five groups (groups 0–4) based on the number of classes of antihypertensive drugs, including β-blockers, renin-angiotensin system (RAS) agents (angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and the renin-inhibitors), calcium channel blockers (CCBs), and other antihypertensive drugs, were prescribed within 90 days after discharge. The primary endpoint was a composite outcome of re-hospitalization associated with AD, referral for aortic surgery, and all-cause death. Results: A total of 3932 non-operated AD patients were included in our study. The most prescribed antihypertensive drugs were CCBs, followed by β-blockers and ARBs. Within group 1, compared to other antihypertensive drugs, patients using RAS agents (aHR, 0.58; p = 0.005) had a significantly lower risk of occurrence of the outcome. Within group 2, the risk of composite outcomes was lower in patients using β-blockers + CCBs (aHR, 0.60; p = 0.004) or CCBs + RAS agents (aHR, 0.60; p = 0.006) than in those using RAS agents + others. Conclusion: For non-operated AD patients, RAS agents, β-blockers, or CCBs should be given in a different strategy of combinations to reduce the hazard of AD-related complications compared to other agents. [ABSTRACT FROM AUTHOR]

Hypertension is the third leading cause of the global disease burden, and while populations live longer, adopt more sedentary lifestyles, and become less economically concerned, the prevalence of hypertension is expected to increase. Pathologically elevated blood pressure (BP) is the strongest risk factor for cardiovascular disease (CVD) and related disability, thus making it imperative to treat this disease. Effective standard pharmacological treatments, i.e., diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blocker (ARBs), beta-adrenergic receptor blockers (BARBs), and calcium channel blockers (CCBs), are available. Vitamin D (vitD) is known best for its role in bone and mineral homeostasis. Studies with vitamin D receptor (VDR) knockout mice show an increased renin–angiotensin–aldosterone system (RAAS) activity and increased hypertension, suggesting a key role for vitD as a potential antihypertensive agent. Similar studies in humans displayed ambiguous and mixed results. No direct antihypertensive effect was shown, nor a significant impact on the human RAAS. Interestingly, human studies supplementing vitD with other antihypertensive agents reported more promising results. VitD is considered a safe supplement, proposing its great potential as antihypertensive supplement. The aim of this review is to examine the current knowledge about vitD and its role in the treatment of hypertension. [ABSTRACT FROM AUTHOR]

Purpose. Randomised controlled trials have shown that renal denervation lowers office and ambulatory blood pressure. The aim of the present study was to evaluate whether patients undergoing renal denervation procedure in a real-life setting have a reduction in antihypertensive drug prescription over the subsequent years. Material and methods. Using the healthcare utilisation database of the Lombardy Region (Italy), the 136 patients who, during the period 2011–2016, were prescribed four or more antihypertensive drugs and underwent renal denervation were included in the study cohort. The number and type of antihypertensive drugs were assessed over the year before and during the three-year period after renal denervation. Results. The median age of the patients was 67 years and 68% of them were men. Based on a multisource comorbidity score, about 40% of patients showed a poor or very poor clinical status. Before renal denervation, the majority of the patients were prescribed four or five antihypertensive drugs. The number of drugs decreased after the denervation and reached 55% after three years. Over the same period, patients prescribed six drugs decreased from 18% to 2%. All antihypertensive drugs were less prescribed throughout the post denervation period. Compared to the year before the denervation, after three years prescription of diuretics was reduced by 15%, calcium channel blockers by 21%, ACE-inhibitors by 32%, angiotensin receptor blockers by 22%, beta-blockers by 20%, and alfa-blockers by 30%. Use of antihypertensive drugs exhibited a reduction also in an age, sex, and clinically matched control group with no renal denervation to an extent, however, much lower than in denervated patients (p-value = 0.013). Conclusion. In the real-life setting, patients who underwent renal denervation had a clearcut reduction in antihypertensive drug prescription over the following years. Patients exhibited a reduction in the prescription of antihypertensive drugs during the three years that followed the denervation procedure The decrease in the number of antihypertensive drugs was marked, started after a relatively short time (six months), and involved all drugs prescribed before the denervation The number of hospitalisations for a cardiovascular event was similar before and after renal denervation Albeit blood pressure values were not recorded in our database, all these findings taken together suggest the renal denervation procedure has a favourable influence on blood pressure control and is not associated with an increase in the risk of major cardiovascular complications [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) and pyelonephritis cause urosepsis, which can become life threating. Sodium‐dependent glucose cotransporter 2 (SGLT2) inhibitors, a class of oral anti‐diabetic drugs, may increase the risk of UTI and pyelonephritis, as observed from their mechanism of action. Patients with diabetes receiving SGLT2 inhibitors are often concomitantly administered other antidiabetic, antidyslipidemic, or antihypertensive drugs. To determine if drug–drug interactions (DDIs) between SGLT2 inhibitors and these medications increased the risk of UTI and pyelonephritis, we analyzed the Food and Drug Administration Adverse Event Reporting System (FAERS) database. We applied Norén's and Gosho's methods for detecting DDIs. FAERS contains records describing 14 526 398 patient characteristics, 54 290 663 drug properties, and 47 252 416 reactions/events. We found 23 drug combinations that could induce UTI and pyelonephritis, such as SGLT2 inhibitors administered with dipeptidyl peptidase‐4 inhibitors, thiazolidinediones, glinides, statins, angiotensin II receptor blockers, and calcium channel blockers. Combination therapy with the drugs detected in our analyses would show potential interactions that could result in UTI and pyelonephritis in patients with diabetes mellitus. However, owing to various limitations, these results must be confirmed by additional analyses. [ABSTRACT FROM AUTHOR]

Background: Drug promotional literatures (DPLs) are one of the well-known promotional activities of pharmaceutical industries which are sometimes inaccurate as well as of poor educational value. Angiotensin receptor blockers (ARBs) are one of the most commonly used antihypertensives. Therefore, this study was done to estimate the accuracy of DPLs on ARBs as per the World Health Organization (WHO) criteria. Aims and Objectives: The aims of this study were to estimate the accuracy of DPLs on ARBs as per the WHO and to estimate the DPLs for types of claims and appropriateness of claims. Materials and Methods: A cross-sectional observational study was carried out for 1 month. All the required information of selected DPLs on ARBs were recorded in a pro forma and were evaluated according to the WHO criteria. Results: In this study, a total of 20 (twenty) DPLs were evaluated only on ARBs. It was observed that none of the DPLs fulfilled all the WHO criteria. In this study, some DPLs made multiple claims, as much as five per DPL. Claims were, further, analyzed and divided into appropriate and inappropriate. We have observed that 65.96% claims were appropriate and 34.04% claims were inappropriate. Conclusion: This type of study can contribute to make prescribing practices rational as promotional activities influence the prescribing behavior of the health-care provider. [ABSTRACT FROM AUTHOR]

Association Between Angiotensin Receptor Blocker Therapy and Incidence of Epilepsy in Patients With Hypertension Doege C, Luedde M, Kostev K. JAMA Neurol. 2022;79(12):1296-1302. doi:10.1001/JAMANEUROL.2022.3413 Importance: Arterial hypertension is associated with an increased incidence of epilepsy. Results from animal studies suggest that angiotensin receptor blocker (ARB) therapy could inhibit epileptic seizures. However, there is a lack of clinical data to support the use of ARB therapy in humans. Objective: To assess whether ARB therapy is associated with a decreased incidence of epilepsy in patients with hypertension. Design, setting, and participants: This cohort study obtained data from the Disease Analyzer database (IQVIA) on patients aged 18 years or older who had hypertension and at least 1 antihypertensive drug prescription. Patients were treated at 1274 general practices between January 2010 and December 2020 in Germany. Data were available for 1 553 875 patients who had been prescribed at least 1 antihypertensive drug. Patients diagnosed with epilepsy before or up to 3 months after the index date were excluded. A total of 168 612 patients were included in propensity score matching. Patients treated with 1 of 4 antihypertensive drug classes (β-blockers, ARBs, angiotensin-converting enzyme inhibitors, and calcium channel blockers [CCBs]) were matched to each other using propensity scores. Main outcomes and measures: The main outcome of the study was the incidence of epilepsy associated with ARB therapy compared with other antihypertensive drug classes. Cox regression models were used to study the association between the incidence of epilepsy and ARBs compared with all other antihypertensive drug classes as a group. Results: The study included a total of 168 612 patients, with 42 153 in each antihypertensive drug class. The mean [SD] age of patients was 62.3 [13.5] years, and 21 667 (51.4%) were women. The incidence of epilepsy within 5 years was lowest among patients treated with ARBs (0.27% at 1 year, 0.63% at 3 years, 0.99% at 5 years) and highest among patients receiving β-blockers and CCBs (0.38% for both β-blockers and CCBs at 1 year; 0.91% for β-blockers and 0.93% for CCBs at 3 years; β-blockers, 1.47%; and CCBs, 1.48% at 5 years). Angiotensin receptor blocker therapy was associated with a significantly decreased incidence of epilepsy (hazard ratio, 0.77; 95% CI, 0.65-0.90) compared with the other drug classes as a group. Conclusions and relevance: In this cohort study of patients with hypertension, ARB therapy was associated with a significantly decreased incidence of epilepsy. The findings suggest antihypertensive drugs could be used as a novel approach for preventing epilepsy in patients with arterial hypertension. [ABSTRACT FROM AUTHOR]

Purpose: Antihypertensive medication is an effective way to control blood pressure. However, some studies reported that it may affect patients' sleep quality during the treatment. Due to the inconsistency of present results, a comprehensive systematic review and network meta-analysis are needed. Methods: Electronic databases (MEDLINE, EMBASE, WEB OF SCIENCE, PUBMED) were searched up to April 10th, 2021 including no restriction of publication status. Randomized controlled trials (RCTs) or quasi-experimental studies or cohort studies were eligible. The network meta-analysis was used within a Bayesian framework. Results: Finally, 16 publications (including 12 RCTs and 4 quasi-experimental studies) with 404 subjects were included in this study. Compared to placebo, the results of the network meta-analysis showed that diuretics were effective in improving sleep apnea with a mean difference (MD) of − 15.47 (95% confidence interval [CI]: − 23.56, − 6.59) which was consistent with the direct comparison result (MD: − 17.91; 95% CI − 21.60, − 14.23). In addition, diuretics were effective in increasing nocturnal oxygen saturation with an MD of 3.64 (95% CI 0.07, 7.46). However, the effects of β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and the others on sleep apnea were not statistically significant. Additionally, the effects of antihypertensive medication on the total sleep time (min), rapid eye movement (%), and sleep efficiency (%) were not statistically significant. Conclusion: Our study found that diuretics could effectively reduce the severity of sleep apnea in hypertensive patients. However, the effects of antihypertensive drugs on sleep characteristics were not found. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the prescribing pattern of antihypertensive drugs and its compliance to the recommendations of Joint National Committee 8 (JNC 8) guidelines and assess the impact of pharmacist led patient counselling on hypertension management. Methods A prospective study was carried out for a period of one year (September 2020–October 2021) among 150 hypertensive patients of various departments in a tertiary care hospital, Kerala, India. All the cases were prospectively analysed to study the pattern of antihypertensive use and patients were counselled with a patient information leaflet. Key findings Out of 150 patients, 53% were women and 47% were men. Majority of patients were aged 60 years and above (66.0%). Diabetes mellitus (26%) was the most common co-morbidity associated with hypertension. About half of the patients had received dual therapy (49%) followed by monotherapy (31.3%), triple therapy (18%) and quadruple therapy (2%). Calcium channel blockers (59.8%) were the most frequently prescribed drug class followed by angiotensin II receptor blockers (30.5%) either alone or in combination for effective control of blood pressure. Cilnidipine (8.7%) was the most commonly used antihypertensive drug followed by telmisartan (8%). It was observed that 80% of prescriptions were adherent to JNC 8 hypertension treatment recommendations. There was a significant difference (P < 0.001) in the knowledge-awareness scores before (18%) and after (52%) patient counselling. Conclusion The study represents the utilisation pattern of antihypertensive drugs. The adherence of antihypertensive medication use to JNC 8 guidelines was high level at the study site but needs to improve further. The study concludes that pharmacist-led counselling plays a vital role in improving patients' knowledge and awareness towards hypertension management. [ABSTRACT FROM AUTHOR]

Purpose: Hypertension is an important risk factor for severe outcomes in patients with COVID‐19, and antihypertensive drugs may have a protective effect. However, the pandemic may have negatively impacted health care services for chronic diseases. The aim of this study was to assess initiations of antihypertensive medicines in patients infected by COVID‐19. Methods: A cohort study including all Swedish residents 20–80 years old with a COVID‐19 positive test compared with an unexposed group without COVID‐19 matched for age, sex, and index date (date of confirmed COVID‐19). Data were collected within SCIFI‐PEARL, a study including linked data on COVID tests, hospital diagnoses, dispensed prescriptions, and socioeconomic data from Swedish national registers. Initiations of different antihypertensive drugs were studied from March 2020 until October 2020. Associations between COVID‐19 and initiation of antihypertensives were assessed by a multivariable Cox proportional hazards model. Results: A total of 224 582 patients (exposed and unexposed) were included. After adjusting for cardiovascular comorbidities and education level, ACEi was the most commonly initiated antihypertensive agent to patients with COVID‐19. Hazard ratio and 95% confidence interval for initiation of drug therapy was 1.83 [1.53–2.19] for ACEi, followed by beta‐blockers 1.74 [1.55–1.95], calcium channel blockers 1.61 [1.41–1.83], angiotensin receptor blockers 1.61 [1.40–1.86], and diuretics 1.53 [1.32–1.77]. Conclusion: All antihypertensive medicines were initiated more frequently in COVID‐19 patients. This can either be associated with hypertension caused by the COVID‐19 infection, more frequent diagnosis of hypertension among people with COVID‐19 since they consult health care, or residual confounding factors not adjusted for in the study. [ABSTRACT FROM AUTHOR]

In 2020, the National Center for Cardiovascular Diseases with National Committee on Hypertension Management in Primary Health Care in China issued revised national clinical practice guidelines on the management of hypertension in primary health care based on the 2018 Chinese guidelines for the management of hypertension. To evaluate adherence to the guidelines, this retrospective study assessed the real-world status of antihypertensive drug prescribing for Chinese patients with hypertension, classified by comorbidity: coronary heart disease, diabetes mellitus, heart failure, stroke, and renal disease. About 1088212 hypertensive patients who received their first prescription for antihypertensive therapy between January 2021 to June 2021, were obtained from a database of Hangzhou Kang Sheng Health Consulting CO., Ltd. Calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) were the most common drugs prescribed for each comorbidity subgroup. Whereas diabetes mellitus or renal disease is a compelling indication for use of renin–angiotensin system inhibitors, CCBs were often administered in these subgroups. The treatment pattern for patients with coronary heart disease was closely similar to that for the overall patient population. Beta-blockers (BBs) were prescribed more frequently for patients with heart failure than for those with other comorbidities. Although antihypertensive drug prescription varied by comorbidity, pharmacological decisions were largely made under Chinese recommendations while physicians could select antihypertensive drugs based on the patients' comorbidities. However, educational initiatives are still necessary to inspire clinicians to better familiarize themselves with the guidelines and manage hypertension comorbid diseases. [ABSTRACT FROM AUTHOR]

Introduction Hypertension is a global burden and prevalence of hypertension increases with age. Various antihypertensive drugs are available for the management of hypertension. The aim of this study is to assess the trend of antihypertensive drugs used and blood pressure (BP) control among patients with hypertension. Methods A cross sectional study was conducted among patients with hypertension prescribed with antihypertensive drugs in Department of Medicine, Nepal Medical College Teaching Hospital. Antihypertensive drugs, number of antihypertensive drugs prescribed in each individual and BP were analyzed. Results Out of 218 patients, 61.5% were female and 38.5% were male. Common age group range from 51-60 years in 28.4% of patients. Diabetes mellitus (23.4%) was the most common comorbid condition. Dual therapy (47.6%) followed by monotherapy (45.9%) was the most common therapy prescribed for patients with hypertension. Most commonly prescribed antihypertensive as monotherapy was Calcium Channel Blockers (CCBs), 29.4% and in dual therapy, CCBs and Angiotensin Receptor Blockers (ARBs), 38.6% were the most commonly prescribed medications. Fixed dose combination of antihypertensive drugs were prescribed in 81.4% patients receiving multiple therapy. Good BP control was observed in 61.2% of patients with hypertension. Conclusion Dual therapy followed by monotherapy was the most common therapy prescribed for the management of hypertension. Calcium channel blockers as monotherapy and CCBs and ARBs as combination therapy were the most common antihypertensive drugs prescribed for hypertension. More than half the patients had controlled BP. A therapeutic audit with more parameters of analysis to provide regular feedback to researchers and prescribers may encourage rational prescribing in hypertension. [ABSTRACT FROM AUTHOR]

Background: Certain classes of antihypertensive medication may have different associations with cognitive impairment.Objective: To examine the association between prevalent use of antihypertensive medications that stimulate (thiazides, dihydropyridine calcium channel blockers, angiotensin type I receptor blockers) versus inhibit (angiotensin-converting enzyme inhibitors, beta-blockers, non-dihydropyridine calcium channel blockers) type 2 and 4 angiotensin II receptors on cognitive impairment among older adults residing in Veterans Affairs (VA) nursing homes for long-term care.Methods: Retrospective cohort study. Long-term care residents aged 65 + years admitted to a VA nursing home from 2012 to 2019 using blood pressure medication and without cognitive impairment at admission. Main exposure was prevalent use of angiotensin II receptor type 2 and 4-'stimulating' (N = 589), 'inhibiting' (N = 3,219), or 'mixed' (N = 1,715) antihypertensive medication regimens at admission. Primary outcome was any cognitive impairment (Cognitive Function Scale).Results: Over an average of 5.4 months of follow-up, prevalent use of regimens containing exclusively 'stimulating' antihypertensives was associated with a lower risk of any incident cognitive impairment as compared to prevalent use of regimens containing exclusively 'inhibiting' antihypertensives (HR 0.83, 95% CI 0.74-0.93). Results for the comparison between 'mixed' versus 'inhibiting' regimens were in the same direction but not statistically significant (HR 0.96, 95% CI 0.88-1.06).Conclusion: For residents without cognitive impairment at baseline, prevalent users of regimens containing exclusively antihypertensives that stimulate type 2 and 4 angiotensin II receptors had lower rates of cognitive impairment as compared to prevalent users of regimens containing exclusively antihypertensives that inhibit these receptors. Residual confounding cannot be ruled out. [ABSTRACT FROM AUTHOR]

Objective: By aggregating the literature, we evaluated the association between use of specific antihypertensive drugs and the risk of hip fractures compared with nonuse.Study Design and Setting: We systematically searched the Pubmed, Embase, and Cochrane databases from inception of each database until July 30, 2020 to identify articles including patients 18 years of age or older reporting on the association between antihypertensive drugs and the risk of hip fracture. Antihypertensive drugs were restricted to thiazides; beta-blockers; calcium-channel blockers; angiotensin-converting enzyme (ACE) inhibitors; and angiotensin receptor blockers. Nonusers encompass all patients that are not using the specific antihypertensive drug that has been reported. Unadjusted odds ratios with 95% confidence intervals (CIs) of the association between antihypertensive drug use and hip fractures were reported. Meta-analysis was performed when a minimum of five studies were identified for each antihypertensive drug class. Quality assessment was done using ROBINS-I tool. The GRADE approach was used to evaluate the certainty of the evidence.Results: Of 962 citations, 22 observational studies were included; 9 studies had a cohort design and 13 studies were case-control studies. No randomized controlled trials were identified. We found very low certainty of evidence that both thiazides (pooled odds ratio: 0.85, 95% CI 0.73 to 0.99, p = 0.04) as well as beta-blockers (pooled odds ratio: 0.88, 95% CI 0.79 to 0.98, p = 0.02) were associated with a reduced hip fracture risk as compared to specific nonuse. One study, reporting on angiotensin receptor blockers, also suggested a protective effect for hip fractures, whereas we found conflicting findings in four studies for calcium-channel blockers and in two studies for ACE inhibitors.Conclusion: Among 22 observational studies, we found very low certainty of evidence that, compared to specific nonuse of antihypertensive drugs, use of thiazides, beta-blockers, and angiotensin receptor blockers were associated with a reduced protective hip fracture risk, while conflicting findings for calcium-channel blockers and ACE inhibitors were found. Given the low quality of included studies, further research -randomized controlled trials- are needed to definitively assess the causal relationship between specific antihypertensive drug classes and (relatively infrequent) hip fractures. [ABSTRACT FROM AUTHOR]

Telmisartan is an antagonist of the angiotensin II receptor used in the management of hypertension (alone or in combination with other antihypertensive agents. It belongs to the drug class of angiotensin II receptor blockers (ARBs). Among drugs of this class, telmisartan shows particular pharmacologic properties, including a longer half-life than any other angiotensin II receptor blockers that bring higher and persistent antihypertensive activity. In hypertensive patients, telmisartan has superior efficacy than other antihypertensive drugs (losartan, valsartan, ramipril, atenolol, and perindopril) in controlling blood pressure, especially towards the end of the dosing interval. Telmisartan has a partial PPARγ-agonistic effect whilst does not have the safety concerns of full agonists of PPARγ receptors (thiazolidinediones). Moreover, telmisartan has an agonist activity on PPARα and PPARδ receptors and modulates the adipokine levels. Thus, telmisartan could be considered as a suitable alternative option, with multi-benefit for all components of metabolic syndrome including hypertension, diabetes mellitus, obesity, and hyperlipidemia. This review will highlight the role of telmisartan in metabolic syndrome and the main mechanisms of action of telmisartan are discussed and summarized. Many studies have demonstrated the useful properties of telmisartan in the prevention and improving of metabolic syndrome and this well-tolerated drug can be greatly proposed in the treatment of different components of metabolic syndrome. However, larger and long-duration studies are needed to confirm these findings in long-term observational studies and prospective trials and to determine the optimum dose of telmisartan in metabolic syndrome. [Display omitted] • Telmisartan has two features including a long half-life and PPARγ activation. • Telmisartan modulates the serum levels of adiponectin, visfatin, TNF-α, and resistin. • Telmisartan improves adherence by reducing the pill number and side effects of drugs. • Large and long-duration studies are needed to confirm these features of telmisartan. • The optimum dose of telmisartan in metabolic syndrome needs to be determined. [ABSTRACT FROM AUTHOR]

In this study, design of experiment approach was used for the development and optimization of a reversed phase HPLC method for the simultaneous determination of hydrochlorothiazide, amlodipine along with three angiotensin II receptor blockers olmesartan, losartan and valsartan in their laboratory-prepared mixtures and in three different commercial pharmaceutical single-pill combinations. The interactions between multiple chromatographic factors were studied using central composite design aiming to optimize both the resolution between the studied drugs and the run time. A total of 20 experiments were carried out and the coefficients of the second-order polynomial regression models were calculated to predict the optimal values of the HPLC method parameters. The significance of the models was evaluated by ANOVA, and the interactions between the three variables were illustrated by three-dimensional response surface plots. In this experimental design, the three studied key factors used for the optimization were A: pH, B: flow rate and C: acetonitrile (organic modifier) %. The five experimental responses observed were the four resolution factors and the run time. Obtained results were analyzed and the optimum chromatographic conditions predicted were 0.05 M potassium dihydrogen phosphate buffer (pH adjusted to 2.66 with ortho-phosphoric acid) and acetonitrile in the ratio (75.9:24.1, %v/v) as the mobile phase at flow rate 1.5 ml/min. Phenomenex Luna® 5 µm CN 100 Å LC column (250 × 4.6 mm) was used for the separation and quantification with photo diode array detection at 250 nm. Under these predicted optimum conditions, baseline separation with minimum resolution of 2.0 and run time less than 12 min were achieved, and the obtained experimental results showed good agreement with the predicted values. The optimized chromatographic separation was validated according to the International Conference on Harmonization guidelines to confirm linearity, specificity, accuracy, precision and robustness. The optimized RP-HPLC method has a wide range of application that can be used in quality control and routine analysis of the studied drugs in their different pharmaceutical single-pill combinations and laboratory mixtures aiming to reduce laboratory wastes, analysis time, cost and effort. [ABSTRACT FROM AUTHOR]

Systemic hypertension, atherosclerosis and vasospasm have been recognized as potential factors that are capable of increasing the risk of glaucoma. Several other factors may contribute to the development and progression of the disease, including systemic drugs used to treat other pathologies. Numerous studies have examined the effect of antihypertensive medication on glaucoma, due to their property of modifying vascular events. Effective hypotensive drugs that lower blood pressure reduce the complications of high blood pressure, including changes in intraocular pressure (IOP). It has been shown that the most significant decrease in IOP was registered in patients taking calcium channel blockers, beta-adrenoblockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers and diuretics. The renin-angiotensin system plays a critical role in the pathophysiology of various ocular diseases by causing inflammation, oxidative stress and angiogenesis. All components are currently present in eye structures and play an important role in ocular pathology: diabetic retinopathy, age-related macular degeneration, glaucoma, retinitis pigmentosa. The use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduces the formation of aqueous humor, increases uveoscleral flow, reduces intraocular pressure and has a protective effect by reducing the inflammatory process, oxidative stress and angiogenesis. [ABSTRACT FROM AUTHOR]

Hypertension is more effectively treated with coadministration of 2 or more antihypertensive drugs than with high‐dose monotherapy. Therefore, calcium channel blockers, angiotensin II receptor blockers, and thiazides are coadministered to treat hypertension. The objective of this study was to compare the pharmacokinetic (PK) profiles of HCP1401, a fixed‐dose combination of amlodipine 5 mg, losartan 100 mg, and chlorthalidone 25 mg, with the separate components (loose combination) of amlodipine/losartan 5/100 mg and chlorthalidone 25 mg. A randomized, open‐label, single‐dose, 2‐way crossover study was conducted. Blood samples for amlodipine and chlorthalidone were collected for up to 144 hours after dosing, whereas those for losartan were collected up to 48 hours after dosing. The PK parameters of these drugs were calculated using a noncompartmental method. Sixty subjects completed the study. The geometric mean ratios and 90% confidence intervals of maximum plasma concentration and area under the concentration–time curve to the last measurable point for amlodipine, losartan, and chlorthalidone were within the conventional bioequivalence range of 0.80 to 1.25. There were no clinically significant changes in safety assessments, and the treatments were well tolerated. The PK characteristics and tolerability profiles of a single oral FDC of amlodipine, losartan, and chlorthalidone were equivalent to those of individual tablets in a loose combination. [ABSTRACT FROM AUTHOR]

Background: Fixed-dose combinations can simplify prescribing, and numerous combination products exist for hypertension and dyslipidemia in South Korea. This study's aim was to compare trends in the consumption of single products versus fixed-dose combinations for hypertension and hyperlipidemia. Methods and findings: We analyzed the Korean national health insurance claims database from January 2015 through December 2019. Consumption of medicines was calculated using the defined daily dose per 1,000 inhabitants per day (DIDs) and expenditures over time. During 2015–2019, the use of antihypertensive drugs increased with an annual growth rate (AGR) of 0.9% for single products and with an AGR of 35.6% for fixed-dose combinations. A notable increase was observed for antihyperlipidemic combination drugs with an AGR of 268.1% compared to single products with 35.7%. For older adults (65+ years), the consumption of drugs for hypertension and hyperlipidemia was 3–4.5 and about 3 times higher, respectively, than in adults aged 20–64 years, and a sharp increase was found in antihyperlipidemic fixed-dose combinations among older adults. A large increase was seen for C09 (agents acting on the renin-angiotensin system) with an AGR of 36.5%, especially C09DB (angiotensin II receptor blockers + calcium channel blockers) was widely used and steeply increased with 114.2%. For antihyperlipidemic drugs, C10AA (HMG CoA reductase inhibitors) accounted for a large share and sharply increased, with 52.1 DIDs in 2019 and with an AGR of 78.4%, whereas C10BA (combinations of various lipid modifying agents) increased 9.6 times from 2.9 DIDs (96 million USD) in 2015 to 27.7 DIDs (912 million USD) in 2019. Conclusion: The findings of increased consumption and drug spending among older adults underscores the need for real-world evidence about health outcomes of fixed-dose combinations in this population. [ABSTRACT FROM AUTHOR]

Aims: Antihypertensive drugs have been implicated in coronavirus disease 2019 (COVID‐19) susceptibility and severity, but estimated associations may be susceptible to bias. We aimed to evaluate antihypertensive medications and COVID‐19 diagnosis and mortality, accounting for healthcare‐seeking behaviour. Methods: A population‐based case‐control study was conducted including 16 866 COVID‐19 cases and 70 137 matched controls from the UK Clinical Practice Research Datalink. We evaluated all‐cause mortality among COVID‐19 cases. Exposures were angiotensin‐converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta‐blockers (B), calcium‐channel blockers (C), thiazide diuretics (D) and other antihypertensive drugs (O). Analyses were adjusted for covariates and consultation frequency. Results: ACEIs were associated with lower odds of COVID‐19 diagnosis (adjusted odds ratio [AOR] 0.82, 95% confidence interval [CI] 0.77‐0.88) as were ARBs (AOR 0.87, 95% CI 0.80‐0.95) with little attenuation from adjustment for consultation frequency. C and D were also associated with lower odds of COVID‐19 diagnosis. Increased odds of COVID‐19 for B (AOR 1.19, 95% CI 1.12‐1.26) were attenuated after adjustment for consultation frequency (AOR 1.01, 95% CI 0.95‐1.08). Patients treated with ACEIs or ARBs had similar odds of mortality (AOR 1.00, 95% CI 0.83‐1.20) to patients treated with classes B, C, D or O or patients receiving no antihypertensive therapy (AOR 0.99, 95% CI 0.83‐1.18). Conclusions: There was no evidence that antihypertensive therapy is associated with increased risk of COVID‐19 diagnosis or mortality; most classes of antihypertensive therapy showed negative associations with COVID‐19 diagnosis. [ABSTRACT FROM AUTHOR]

Aprocitentan (ACT-132577) is an orally active, dual endothelin-1 (ET-1) receptor antagonist that prevents the binding of ET-1 to both ETA/ETB receptors. It is an active metabolite of macitentan (obtained by oxidative depropylation), an orphan drug used for the treatment of pulmonary arterial hypertension. Aprocitentan is highly bound to plasma proteins and is eliminated in both urine and feces. It is well tolerated across all doses (up to 600 mg with single dose and 100 mg once a day at multiple doses). Its pharmacokinetic profile shows a half-life of 44 h, fitting a once-daily dosing regimen with plasma ET-1 concentrations (reflecting ET receptor antagonism), significantly increasing with doses ≥ 25 mg. Only minor differences in exposure between healthy females and males, healthy elderly and adult subjects, fed and fasted conditions, and renal function have been observed. Aprocitentan in patients with resistant hypertension is currently under investigation in the PRECISION phase III trial (ClinicalTrials identifier: NCT03541174). Nonetheless, results of pre-clinical data and studies in humans support the potential role of aprocitentan in this clinical setting. The absolute blood pressure (BP) reductions with aprocitentan are in the ranges established as a surrogate for reduction in cardiovascular morbidity in hypertension. Significant changes in BP with aprocitentan are observed within 14 days, and its BP-lowering effects have also been documented with ambulatory BP monitoring. Finally, aprocitentan enhances the BP-lowering effects of other antihypertensive drugs, including renin-angiotensin-system blockers. In conclusion, aprocitentan ameliorates the effects of ET-1 and could potentially reduce BP and provide broader cardiovascular protection in patients with resistant hypertension. Available data support the hypothesis that this new agent could expand our antihypertensive arsenal in resistant hypertension, making aprocitentan an attractive candidate for further large-scale trials. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19), the first pandemic caused by a human infecting coronavirus, has drawn global attention from the first time it appeared in Wuhan city of China in late December 2019. Detection of the responsible viral pathogen, named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by WHO, and its possible pathogenesis lead to the forming of many hypotheses about the factors that may affect the patients' outcome. One of the SARS-CoV-2 infection concerns was the potential role of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19 patients' morbidity and mortality. Studies demonstrated that because SARS-CoV-2 uses human ACE2 cell receptors as an entry receptor to invade the cells, there might be an association between antihypertensive drugs such as RAAS inhibitors (specifically ACEIs and ARBs) and the COVID-19 disease. Data are scarce and conflicting regarding ACEI or ARB consumption and how it influences disease outcomes, and a single conclusion has not been reached yet. According to the literature review in our article, the most evidentially supported theory about the use of RAAS inhibitors in COVID-19 is that these medications, including ACEI/ARB, are not associated with the increased risk of infection, disease severity, and patient prognosis. However, further studies are needed to support the hypothesis. [ABSTRACT FROM AUTHOR]

Stroke is the second most common cause of mortality worldwide and the third most common cause of disability. Stroke causes and hemodynamic consequences are heterogeneous, making blood pressure management in stroke patients complex. Knowing that hypertension is the most prevalent risk factor for stroke, the use of antihypertensive drugs to reduce blood pressure is also essential for the prevention of cardiovascular events before and after stroke. Evidence from clinically relevant studies demonstrates a reduction in morbidity and mortality due to angiotensin type-1 receptor (AT1) blockers. In excessive activity in the brain, this receptor can promote exaggerated sympathetic and hormonal responses caused by stress, vulnerability to cerebrovascular ischemia, and brain inflammation. In addition to its preventive effect, the antihypertensive drug olmesartan medoxomil has shown promising activity in the immediate treatment of both ischemic and hemorrhagic stroke. Olmesartan (OLM) belongs to the family of angiotensin receptor blockers (ARBs) and acts as an inverse agonist with high selectivity and potency for the AT1 receptor. Thus, the present work describes the profile of the AT1 receptor in terms of binding energies and intermolecular interactions with this FDA-approved drug. The X-ray crystallographic structure of the OLM-AT1 system is considered, and the Electrostatically Embedded Molecular Fractionation with Conjugate Caps (EE-MFCC) scheme is applied within a dispersion-corrected Density Functional Theory (DFT-D) framework, taking into account the B97D/aug-cc-pVTZ level of theory. We investigated the binding energies of 105 residues presented within a pocket radius of 10 Å, predicted the energetic relevance of the olmesartan regions and the influence of each protein segment on OLM-AT1 binding. Finally, our results demonstrate that the total binding energy in the pocket ligand is higher in acidic environments, proposing that OLM can promote its neuroregenerative role longer than in the physiological environment, corroborating its use post-stroke. [ABSTRACT FROM AUTHOR]

Biaryl compounds are an important class of aromatic compounds used for the synthesis of antiviral, antihypertensive, and antifungal drugs. The familiar methods for the synthesis of biaryl compounds are Pd-, Ni-catalyzed couplings reactions, such as Suzuki, Negishi and Kumada reactions. Hypertension is a medical condition in which the blood pressure against artery wall is high enough to increase the risk of heart disease and stroke. Angiotensin receptor blockers (ARBs) are one of the most effective and commonly prescribed antihypertensive agents. o-Tolyl benzonitrile (OTBN) is the common building block for the synthesis of the sartan series of drug molecules (ARBs), such as candesartan, irbesartan, losartan, tasosartan, and valsartan. The classical methods for the synthesis of OTBN are Pd-catalyzed, Ni-catalyzed Suzuki coupling reactions. The other high yield methods for the synthesis of OTBN are Ni-catalyzed Kumada coupling, and desulfinating cross-coupling using Pd-catalyst. The Ni-catalysts could be an alternative to the expensive Pd-catalyst, as cost is a factor for bulk manufacturing of this building block. Although there are few reports of OTBN synthesis using desulfinating cross coupling, this method has opened a new avenue. [ABSTRACT FROM AUTHOR]