Antihypertensive Research Articles

Daily versus Twice Daily Nifedipine for Blood Pressure Control in Pregnancy and Postpartum.

The objective of this study was to compare 60mg daily (QD) extended released (XR) nifedipine to 30mg twice daily (BID) for blood pressure (BP) control antepartum and postpartum. This is a retrospective chart review conducted at the Mount Sinai Health System. Patients admitted from 1/1/2015-4/30/2021, diagnosed with a hypertensive disorder of pregnancy, who received nifedipine XR 30mg BID or 60mg QD for intrapartum or postpartum BP control were included. Primary outcome was need for up titration (i.e., need for increase in nifedipine dose or addition of another anti-hypertensive) after reaching one of the study doses (30mg BID or 60mg QD). Patients were excluded if they had preexisting renal disease or were already on oral anti-hypertensives. In a 1:1 ratio between single and twice daily dosing groups, the sample size needed to detect a 20% difference in up-titration rate to achieve 0.80 power is 97 patients per group, for a total of 194 patients. This is based on a Pearson Chi-square test with a significance level of 0.05. 237 patients were included, 139 (59%) received 30 mg BID and 98 (41 %) 60 mg QD. There was no statistically significant difference in the need for increase in nifedipine dose or addition of another oral anti-hypertensive agent between those receiving 30mg BID versus 60mg QD (33.8% vs 35.7%; aOR (95% CI): 0.90 (0.50-1.60); p=0.71). There was no difference in need for emergency hypertensive treatment after reaching study dose (p=0.19) or readmission for BP control between groups (p>0.99). These findings suggest that BID dosing does not confer better blood pressure control in the antepartum or postpartum periods. Thus, daily dosing is reasonable and may be preferable for patient convenience and compliance.

A newly developed method for assessing co-exposure to free dose combinations: a proof-of-concept study using antihypertensive medications in Danish registers

BackgroundElevated blood pressure is a major risk factor for severe medical conditions. Adherence to antihypertensive medication, especially in free-dose combinations, poses a significant challenge. This study aims to develop a novel method for assessing co-exposure to free-dose antihypertensive medications using secondary data sources.MethodsA register-based cohort study was conducted on individuals aged 65 years or older in Denmark who initiated antihypertensive therapy from 1996 to 2016 and followed for 730 days from the index date. A new method was developed to assess co-exposure to antihypertensive medications through redeemed prescriptions, treatment episodes, and overlapping medication events. The method's accuracy was evaluated using a random sample of 400 individuals.ResultsA total of 1,021,819 individuals were included in the study, with a mean age of 68.8 years, and 53.7% were women. The method achieved 100% accuracy in identifying co-exposure periods. During the early stage of the follow-up (0–180 days), 54.1% of individuals were co-exposed to at least two antihypertensive medications, while 37.5% were co-exposed during the late stage of the follow-up period (181–730 days). The most frequent antihypertensive combinations included bendroflumethiazide and potassium with either amlodipine or enalapril in the early (13.2% and 12.5% of patients, respectively) and late stages (16.9% and 15.0% of patients, respectively).ConclusionsThe newly developed method effectively assesses co-exposure to antihypertensive medications, overcoming previous limitations. The findings reveal common co-exposure combinations and evolving trends in antihypertensive medication use among older individuals, reflecting changes in clinical practice and guidelines over two decades.

Antihypertensive Drug Recommendations for Reducing Arterial Stiffness in Patients With Hypertension: Machine Learning-Based Multicohort (RIGIPREV) Study.

High systolic blood pressure is one of the leading global risk factors for mortality, contributing significantly to cardiovascular diseases. Despite advances in treatment, a large proportion of patients with hypertension do not achieve optimal blood pressure control. Arterial stiffness (AS), measured by pulse wave velocity (PWV), is an independent predictor of cardiovascular events and overall mortality. Various antihypertensive drugs exhibit differential effects on PWV, but the extent to which these effects vary depending on individual patient characteristics is not well understood. Given the complexity of selecting the most appropriate antihypertensive medication for reducing PWV, machine learning (ML) techniques offer an opportunity to improve personalized treatment recommendations. This study aims to develop an ML model that provides personalized recommendations for antihypertensive medications aimed at reducing PWV. The model considers individual patient characteristics, such as demographic factors, clinical data, and cardiovascular measurements, to identify the most suitable antihypertensive agent for improving AS. This study, known as the RIGIPREV study, used data from the EVA, LOD-DIABETES, and EVIDENT studies involving individuals with hypertension with baseline and follow-up measurements. Antihypertensive drugs were grouped into classes such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, diuretics, and combinations of diuretics with ACEIs or ARBs. The primary outcomes were carotid-femoral and brachial-ankle PWV, while the secondary outcomes included various cardiovascular, anthropometric, and biochemical parameters. A multioutput regressor using 6 random forest models was used to predict the impact of each antihypertensive class on PWV reduction. Model performance was evaluated using the coefficient of determination (R2) and mean squared error. The random forest models exhibited strong predictive capabilities, with internal validation yielding R2 values between 0.61 and 0.74, while external validation showed a range of 0.26 to 0.46. The mean squared values ranged from 0.08 to 0.22 for internal validation and from 0.29 to 0.45 for external validation. Variable importance analysis revealed that glycated hemoglobin and weight were the most critical predictors for ACEIs, while carotid-femoral PWV and total cholesterol were key variables for ARBs. The decision tree model achieved an accuracy of 84.02% in identifying the most suitable antihypertensive drug based on individual patient characteristics. Furthermore, the system's recommendations for ARBs matched 55.3% of patients' original prescriptions. This study demonstrates the utility of ML techniques in providing personalized treatment recommendations for antihypertensive therapy. By accounting for individual patient characteristics, the model improves the selection of drugs that control blood pressure and reduce AS. These findings could significantly aid clinicians in optimizing hypertension management and reducing cardiovascular risk. However, further studies with larger and more diverse populations are necessary to validate these results and extend the model's applicability.

Pharmacological interactions in novel oral anticoagulants, statins, and hypertension drugs in patients treated with direct-acting antivirals for hepatitis C: a Delphi Consensus project

To date, no retrospective or real-world studies have comprehensively examined the interactions between direct-acting antivirals (DAAs) and widely used medications such as novel oral anticoagulant, statins, and antihypertensive agents. However, clinical experience from key opinion leaders may guide physicians in managing these interactions in patients undergoing DAA treatment. This study aims to elucidate the interactions between DAAs and commonly prescribed drugs in patients with prevalent comorbidities (e.g., type II diabetes, hypertension, and dyslipidemia), with a particular focus on those receiving polytherapy with cardiovascular drugs while undergoing DAA treatment for hepatitis C. The clinicians’ experience was combined with input from a qualified expert panel using a Consensus Delphi approach. The findings of this study offer essential and practical recommendations that can be readily applied in everyday clinical practice, helping physicians in managing hepatitis C virus patients undergoing DAA therapy.

Comparative Economic and Clinical Utility of Adding Candesartan for Hypertension Management

Introduction: Antihypertensive drugs require high costs because they are used over a long period. Therefore, consideration is needed in drug selection requirements, effectiveness, and price. This study aimed to see the beneficial results of hypertension therapy and the non-medical costs incurred by patients using cost-utility analysis (CUA). Method: This research was a prospective study. The incremental Cost-Utility Ratio (ICUR) of antihypertensive treatment was calculated using cost-utility data obtained through EQ-5D-5L questionnaires from outpatients at Universitas Andalas Hospital in January- March 2023 who met the inclusion and exclusion criteria. The costs used were from a patient perspective, consisting of direct medical and non-medical costs. This study compared standard treatment (amlodipine) with the addition of candesartan. Results: The number of respondents in this study was 67, consisting of 23 respondents (34.33%) using amlodipine alone and 44 respondents (65.67%) using the amlodipine-candesartan combination. The ICUR value obtained was IDR7,318,674/QALY. The difference in the average utility value of the amlodipine-candesartan combination with amlodipine alone is -0.02, and the difference in cost is -IDR12,224. Based on the cost-utility diagram, the amlodipine-candesartan combination group is included in the southwest quadrant (quadrant III), which illustrates that the cost required for the amlodipine-candesartan combination group is lower than the cost of the amlodipine single treatment group and the outcome is also not better (slightly lower or the same). Conclusion: It was recommended to prioritize using amlodipine alone for hypertension management, as it provides similar outcomes to the amlodipine-candesartan combination while incurring lower costs.

Rationale and Design of a Randomized, Open-Label, Parallel-Group Study of Esaxerenone Versus Angiotensin Receptor Blockers in Older Patients With Uncontrolled Hypertension on Calcium Channel Blocker Monotherapy (ESCORT-HT).

Angiotensin II receptor blockers (ARBs) and calcium channel blockers (CCBs) are commonly prescribed as first- and second-line treatments for older Japanese patients with hypertension. However, due to age-related decline in renin activity, the effectiveness of ARBs may decrease. This highlights the need for other antihypertensive agents to be used in combination with CCBs to replace ARBs for more effective blood pressure (BP) control. The ESCORT-HT study is a multicenter, randomized, controlled, open-label, parallel-group study with a 4-week run-in period and 12-week treatment period. This study aims to evaluate the efficacy of esaxerenone as a second-line treatment for hypertension and to determine whether its BP-lowering effect is noninferior to that of ARBs in older patients with uncontrolled hypertension on CCB monotherapy. The safety profiles of esaxerenone and ARBs will also be evaluated. Patients will be randomly assigned in a 1:1 ratio to receive either esaxerenone or an ARB. The primary efficacy endpoint will be the change from baseline in morning home systolic BP at the end of the treatment period. The BP-lowering effect of esaxerenone will be considered noninferior to that of ARBs if the upper limit of the two-sided 95% confidence interval (CI) for the difference in systolic BP change between esaxerenone and ARB is <3.8mmHg, and will be considered superior if the upper limit of the two-sided 95% CI is <0. The findings may elucidate the possible benefits of earlier use of mineralocorticoid receptor blockers in combination with CCBs in older patients with essential hypertension.

Antihypertensive Deprescribing and Cardiovascular Events Among Long-Term Care Residents

The practice of deprescribing antihypertensive medications is common among long-term care residents, yet the effect on cardiovascular outcomes is unclear. To compare the incidence of hospitalization for myocardial infarction (MI) or stroke among long-term care residents who are deprescribed or continue antihypertensive therapy. This comparative effectiveness research study used target trial emulation with observational electronic health record data from long-term care residents aged 65 years or older admitted to US Department of Veterans Affairs community living centers between October 1, 2006, and September 30, 2019, and taking at least 1 antihypertensive medication. Analyses were conducted between August 2023 and August 2024. A reduction in the number of antihypertensive medications or dose (by ≥30%), assessed using barcode medication administration data. Incidence of MI and stroke hospitalization up to 2 years was assessed using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. A pooled logistic regression model with inverse probability of treatment weighting (IPTW) and inverse probability of censoring weighting (IPCW) was used to estimate per-protocol effects. Of 13 096 long-term care residents (97.4% men; median age, 77 years [IQR, 70-84 years]) taking antihypertensive medication, 17.8% were deprescribed antihypertensive medication over a period of 12 weeks. The estimated unadjusted cumulative incidence of stroke or MI hospitalization over 2 years was similar among residents who were and were not deprescribed antihypertensives in per-protocol analyses (11.2% vs 8.8%; difference, 2.4 percentage points [95% CI, -2.3 to 7.1 percentage points]). Participant characteristics were balanced after applying IPTW and IPCW; all standardized mean differences were less than 0.05. After full adjustment for confounding and informative censoring, the per-protocol analysis results showed no association of antihypertensive deprescribing with MI or stroke hospitalization (hazard ratio, 0.93; 95% CI, 0.70-1.26). In this comparative effectiveness research study, deprescribing antihypertensive medication was not associated with risk of hospitalization for MI or stroke in long-term care residents. These findings may be informative for long-term care residents and clinicians who are considering deprescribing antihypertensive medications.

Long working hours and health in Denmark: a post hoc analysis of three cohort studies

BackgroundTo protect the safety and health of workers, national legislations often stipulate an upper limit to weekly working time. The purpose of the present study was to provide information that may facilitate the obtainment of evidence-based limits to weekly working time.ObjectiveTo estimate incidence rate ratios (RRs) of (i) hospital treatment or death due to accidental injuries, (ii) redeemed prescriptions for psychotropic drugs and (iii) redeemed prescriptions for antihypertensive drugs, respectively, as continuous functions of weekly working hours among employees in the general population of Denmark.MethodsBaseline data on working time arrangements were obtained from the Danish Labor Force Surveys of 1999–2013. Follow-ups with a mean duration of 1.8, 4.0 and 6.6 years for accidental injuries, psychotropic drugs and antihypertensive drugs, respectively, were accomplished through national registers. Adjusted RRs were obtained through Poisson regression in the interval 32–80 weekly working hours (wwh). The reference (standard working hours) was set at 37 wwh. RR estimates were interpreted in accordance with a modified version of Monson’s guide to strength of associations, in which a RR in the open interval 0.83 to 1.2 is classified as ‘no association’ (too weak to be detected by observational studies).ResultsThe estimated RRs as well as the upper and lower limits of their 95% confidence intervals lied within the no-association zone throughout the intervals 32–76, 32–64 and 32–69 wwh, for accidental injury, psychotropic drug use and antihypertensive drug use, respectively. The estimated RRs for psychotropic drug use decreased from 1.08 (95% CI: 1.03–1.13) at 32 wwh to 0.96 (0.93–0.99) at 45 wwh. They thereafter increased to 1.00 (0.95–1.06) at 55 wwh and 1.31 (1.08–1.63) at 80 wwh. The estimated RRs for accidental injury and antihypertensive drug use increased slowly from 1.00 at 37 wwh to 1.04 (0.88–1.24) and 1.11 (0.94–1.31), respectively, at 80 wwh.ConclusionThese results suggest that, from a societal perspective, the effect of wwh on the rates of these types of morbidity is negligible throughout the interval 32–64 wwh.

Androgen deprivation therapy and cardiological risks in patients with prostate cancer. Are all drugs the same?

Androgen deprivation therapy and cardiological risks in patients with prostate cancer. Are all drugs the same?

INDENTIFIKASI PERMASALAHAN TERKAIT PENGOBATAN PADA PASIEN DISLIPIDEMIA KOMORBID DIABETES MELITUS DENGAN TERAPI STATIN DI SALAH SATU RUMAH SAKIT KOTA BANDUNG TAHUN 2023

ABSTRACT Dyslipidemia and type II diabetes mellitus (DM) can occur simultaneously and can mutually worsen the patient's condition. The complexity of treatment in patients with such comorbidities potentially increases the risk of treatment-related problems. This study aims to determine the demographics of patients with type II DM comorbid dyslipidemia in one of the hospitals in Bandung City in 2023 and describe the incidence of treatment problems. This descriptive study reviewed 92 patient medical records that met the research criteria. The classification method for identifying problems related to treatment refers to Basger et al. 2015. The results showed that patients with type II DM comorbid dyslipidemia on statin therapy were dominated by women (55.43%) and elderly (59.78%). The most frequent incidence of treatment-related problems was in the subcategory of inappropriate drug combinations. There were 78 cases resulting in increased therapeutic effect and the most common was related to the prescription of lansoprazole with atorvastatin; 55 cases of interactions resulting in reduced therapeutic effect, of which the most common was related to the prescription of clopidogrel with atorvastatin. There were 4 cases that resulted in hypersensitivity reactions involving allopurinol and antihypertensive drugs. It can be concluded that clinical pharmacists intervene in reviewing patient care by considering the risks and benefits of such a combination for the patient.

Guidelines for the management of hypertension in CKD patients: where do we stand in 2024?

Until recently, major bodies producing guidelines for the management of hypertension in patients with chronic kidney disease (CKD) disagreed in some key issues. In June 2023, the European Society of Hypertension (ESH) published the new 2023 ESH Guidelines for the management of arterial hypertension a document that was endorsed by the European Renal Association. Several novel recommendations relevant to the management of hypertension in patients with CKD appeared in these guidelines, which have been updated to reflect the latest evidence-based practices in managing hypertension in CKD patients. Most of these are in general agreement with the previous 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines-some reflect different emphasis on some topics (i.e. detailed algorithms on antihypertensive agent use) while others reflect evolution of important evidence in recent years. The aim of the present review is to summarize and comment on key points and main areas of focus in patients with CKD, as well as to compare and highlight the main differences with the 2021 KDIGO Guidelines for the management of blood pressure in CKD.

Prosopis africana extract inhibits critical enzymes associated with hypertension in vitro and in cyclosporine-induced hypertensive rats

ObjectiveThis study evaluated the antihypertensive properties of leaf extracts of Prosopis africana (PA) in vitro and in hypertensive rats. MethodsEthanol (ELPA) and differential solvent fractions [ethyl-acetate (EAPA), butanol (BLPA), and aqueous (ALPA)] were prepared using standard protocols. Hypertension was induced in female albino Wistar rats intraperitoneally using cyclosporine (25 mg/kg/day) while extracts were administered via oral route. Forty female rats were grouped into 5 (n = 8). Group 1 received 2 ml distilled water, Group 2: (cyclosporine + 2 ml distilled water); Group 3: cyclosporine + captopril (10 mg/kg/day); Group 4: cyclosporine + 1000 mg/kg ELPA and Group 5: cyclosporine + 1500 mg/kg ELPA. The blood pressure of anesthetized rats was measured using LabScribe coupled to a Lab-Trax-4/24T, and the activities of angiotensin-converting enzyme (ACE), arginase, phosphodiesterase-5 (PDE-5), acetylcholinesterase (AChE) and adenosine deaminase (ADA) were evaluated using standard methods. ResultsAll the fractions exerted significantly (p < 0.05) higher ACE inhibitory effect (ELPA = 64.36 ± 0.50%; EAPA = 86.31 ± 0.60%; BLPA= 85.28 ± 2.30 % ; ALPA= 82.27 ± 2.10 % ) than the reference, lisinopril (40.22±0.50 % ); while the butanol fraction (67.05±0.40 % ) showed higher PDE-5 inhibition than the reference, sildenafil (23.06±0.70 % ). Administration of cyclosporine caused notable (p < 0.05) elevation of systolic/diastolic blood (131.00 ± 1.22/93.25 ± 1.49 mmHg) pressure plus elevated heart rate when in comparison with the normotensive rats (106.25 ± 1.65/85.25 ± 1.18 mmHg). Treatment of hypertensive rats with ELPA significantly reduced elevated activities of ACE, PDE-5, AChE, and arginase to values that are not significantly (p < 0.05) different from those of the rats treated with the reference drug. ConclusionThis result could validate the use of P. africana as an antihypertensive agent in folklore.

A randomized clinical trial evaluating Hydralazine’s efficacy in early-stage Alzheimer’s disease: The EHSAN Study

Alzheimer’s Disease (AD), a neurodegenerative disorder escalating worldwide, remains incurable with existing interventions merely mitigating symptoms. Hydralazine, an antihypertensive agent, has displayed neuroprotective potential in AD animal models via amplification of mitochondrial functionality and stimulation of stress management and repair pathways. Nevertheless, its effectiveness and tolerability in human AD cohorts are yet to be confirmed. This study protocol describes the design of an ongoing, single-center, randomized, triple-blind, placebo-controlled trial to assess hydralazine’s effects on cognitive function in mild to moderate -stage AD patients. We will enroll 424 patients aged 50 and older, meeting NINCDS-ADRDA criteria for probable AD with Mini-Mental State Examination scores from 12–26. They’ll be randomly assigned to receive either hydralazine HCL (25 mg, thrice daily) or a placebo for 12 months. The primary outcome is the Alzheimer’s Disease Assessment Scale change from baseline to 12 months. Secondary outcomes include various measures using Lawton instrumental activities of daily living scale, neuropsychiatry inventory, and caregiver activity survey. This trial will explore the potential benefits and risks of hydralazine in mild to moderate AD treatment. It’s the first trial examining hydralazine’s impact on mild to moderate -stage AD in human and is registered at the Iranian Registry of Clinical Trials (IRCT20200711048075N1, registered 29/07/2020) and ClinicalTrials.gov (NCT 04,842,552AQ, registered 13/04/2021). Ethics approval was granted by the Research Ethics Committee of the National Institute for Medical Research Development (IR.NIMAD.REC.1398.424), following the SPIRIT Statement guidelines. Findings will be disseminated via peer-reviewed publications and conferences. This inaugural human clinical trial evaluates hydralazine’s impact on patients in the mild to moderate AD. Executed with a randomized, triple-blind, placebo-controlled methodology, this study incorporates a significant sample size and an extended monitoring duration. Multiple parameters, including cognitive capabilities, will be assessed. Potential limitations include the inherent homogeneity of the AD cohort, the lack of biomarker assays, and the unpredictable progression of the disease. Notably, the study might not elucidate the protracted effects of hydralazine beyond a 12-month period. Another limitation of our clinical trial is that patients were diagnosed with Alzheimer’s disease based solely on clinical evaluation and MRI findings, without the inclusion of specific biomarkers, which may impact the accuracy and specificity of the diagnosis. Trial registration: Iranian Registry of Clinical Trials (IRCT20200711048075N1, registered 29/07/2020) and ClinicalTrials.gov (NCT 04,842,552, registered 13/04/2021).

Systematic review of Mendelian randomization studies on antihypertensive drugs

BackgroundWe systematically reviewed Mendelian randomization (MR) studies and summarized evidence on the potential effects of different antihypertensive drugs on health.MethodsWe searched PubMed and Embase for MR studies evaluating the effects of antihypertensive drug classes on health outcomes until 22 May 2024. We extracted data on study characteristics and findings, assessed study quality, and compared the evidence with that from randomized controlled trials (RCTs).ResultsWe identified 2643 studies in the search, of which 37 studies were included. These studies explored a wide range of health outcomes including cardiovascular diseases and their risk factors, psychiatric and neurodegenerative diseases, cancer, immune function and infection, and other outcomes. There is strong evidence supporting the protective effects of genetically proxied antihypertensive drugs on cardiovascular diseases. We found strong protective effects of angiotensin-converting enzyme (ACE) inhibitors on diabetes whereas beta-blockers showed adverse effects. ACE inhibitors might increase the risk of psoriasis, schizophrenia, and Alzheimer’s disease but did not affect COVID-19. There is strong evidence that ACE inhibitors and calcium channel blockers (CCBs) are beneficial for kidney and immune function, and CCBs showed a safe profile for disorders of pregnancy. Most studies have high quality. RCT evidence supports the beneficial effects of ACE inhibitors and CCBs on stroke, diabetes, and kidney function. However, there is a lack of reliable RCTs to confirm the associations with other diseases.ConclusionsEvidence of the benefits and off-target effects of antihypertensive drugs contribute to clinical decision-making, pharmacovigilance, and the identification of drug repurposing opportunities.

A case report on the management of pemphigus vulgaris along with comorbid conditions in geriatric patient

Pemphigus vulgaris (PV) is a rare autoimmune blistering disease characterized by intraepidermal acantholysis, which affects the skin and mucous membranes. The patient was a 65-year-old female presenting with a history of type 2 diabetes mellitus and hypertension. There were fluid-filled, pruritic lesions that progressively spread from the forearms and neck to the face and other areas. Histopathological and immunofluorescence studies confirmed PV. She was treated with intravenous hydrocortisone, antibiotics, antihistamines, and supportive measures. The basic chronic kidney disease needed to be considered, and thus, conservative treatment was opted for. On being discharged, she was given a tapering dose of prednisolone along with other drugs that were prescribed for antidiabetic and antihypertensive drugs. It is a case that emphasizes the early and multidisciplinary need for diagnosis in PV, especially when comorbidities are present. Further research is also sought to improve the procedures of diagnosis and treatment of PV.

Risk factors for lenvatinib-induced hypertension in patients with hepatocellular carcinoma: A retrospective study.

Lenvatinib mesylate (LEN) is an orally administered tyrosine kinase inhibitor used to treat various cancers, including hepatocellular carcinoma (HCC). LEN therapy for HCC is associated with a high incidence of adverse events, including hypertension (HTN). However, the risk factors associated with LEN therapy remain unclear. This study investigated the incidence of LEN-induced HTN (LENiHTN), and the relationship between HTN incidence and patient demographics in patients with HCC receiving LEN therapy. This was a single-centre, retrospective study of patients with HCC who received LEN therapy between 19 April 2018 and 30 September 2020. The observation period was from 1week before the start to 1month after the end of LEN administration. Seventy-five patients with HCC were enrolled. Any grade LENiHTN was found in 74.7% of patients. Among patients with LENiHTN, the use of 2 or more antihypertensive agents before starting LEN was less common (P=.007); serum potassium (K) and albumin-bilirubin score (ALBI) were lower (P=.013 and 0.038, respectively); and albumin (Alb) was higher (P=.025). The cut-off values of K, Alb and ALBI for HTN were estimated at 4.1mEq L-1, 3.1g dL-1 and -1.736, respectively. In the multivariable analysis, low K (adjusted HR: 2.078) and low ALBI (adjusted HR: 2.845) were independent risk factors for LENiHTN. Low K, high Alb and low ALBI were independent risk factors for LENiHTN. Systematic evaluation of HTN risk and early intervention for HTN prevention among high-risk patients can markedly enhance LEN therapy efficacy and use.

In vitro comparative quality evaluation of different brands of Amlodipine Tablets Commercially available in Jimma Town, South-western Ethiopia.

The incidence of hypertension in persons 25 years of age and older is estimated to be 46% in Africa, where it is still very common. This concerning rate could be explained by the pharmaceutical markets' accessibility to poor quality antihypertensive drugs. Thus, the purpose of this study was to evaluate and compare the quality different brands of Amlodipine Tablets Commercially available in Jimma Town, South-western Ethiopia. The quality control test was conducted from August 30, 2019 to February 27, 2020 at Jimma University in the Laboratory of Drug Quality Control (JuLaDQ). The laboratory test was carried out in accordance with WHO inspection guidelines and United States Pharmacopeia. A statistically significant was considered when P<0.05. For further comparison of the in-vitro dissolution profiles of amlodipine tablets, model-independent model-dependent parameters and statistical Dunnetts tests for ensuring bioequivalence were used to further compare the in-vitro dissolution profiles. With the exception of brand AMD-5 (1/10), the remaining nine (n = 9) brands were within WHO visual inspection criteria. The quality control parameters such as friability, weight variation, identity, assay, and dissolution test were within the United States Pharmacopeia. The model independent parameters (f1, and f2) confirmed that, all generic products were bio-equivalence, and interchangeable with comparator product. The model dependent approaches revealed the Weibull model (AMD-10), the Zero order (AMD-3), and the Korsemeyer-Peppas models were the most effective predictions for the release of the pharmaceutical substance from the dosage form. The Korsemeyer-Peppas model (r2 ≥0.9695) was the best descriptive model for determining the amlodipine drug kinetics from the point of view of all brands examined. The evaluated amlodipine brand tablets were in line with quality standards. The model independent methods confirmed that the generic brand tablets were interchangeable in clinical practice. The tested products follow more than two drug release kinetics. The study revealed a manifest discrepancy in the dissolution profiles' releases. Therefore, it is strongly advised to use appropriately designed dissolution profile evaluation methods with various pH values in the dissolution media, as well as to do comprehensive visual inspections. This will make it easier to do a thorough investigation of any potential quality issues that might be related to various generic products available in the pharmaceutical market.

Design and application of intramolecular arylogous nitroaldol condensation to access 2-aryl-benzofuran and -indole derivatives and formal synthesis of saprisartan.

This study presents the design and application of intramolecular arylogous nitroaldol (Henry) condensation. A transition metal-free, base-mediated reaction of ortho-heteroatom-substituted aryl aldehydes/ketones and 2-nitrobenzyl (pseudo)halides has been developed to access a wide range of 2-(2-nitroaryl)benzofuran/2-(2-nitroaryl)indole derivatives in high yields. The reaction appears to proceed through O-/N-benzylation and intramolecular arylogous nitroaldol condensation. The application potential of the presented strategy has been demonstrated in the formal synthesis of anti-hypertensive agent saprisartan through the efficient synthesis of an advanced key intermediate, which has been accomplished in a ten-fold high overall yield by using resourceful, inexpensive and less-toxic reagents compared to the known methods.

Deucravacitinib in Moderate to Severe Plaque Psoriasis: Comorbidities and Use of Prior and Concomitant Medication in Patients Enrolled in the Phase 3 POETYK PSO-1 and PSO-2 Trials

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was superior to placebo and apremilast in two global, phase 3 trials, POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751), in moderate to severe plaque psoriasis. Here, we evaluate the comorbidities present at baseline and use of prior and concomitant medications in the pooled POETYK PSO-1 and PSO-2 trial populations to more comprehensively describe the medical history of individuals who participated in the deucravacitinib phase 3 trials. Methods: In POETYK PSO-1 and PSO-2, adults with moderate to severe plaque psoriasis were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. The rates of baseline comorbidities and medications received before and concomitantly with deucravacitinib in the pooled POETYK PSO trials were assessed. Medication classes evaluated included antidiabetic, antihypertensive and cardiovascular, lipid-reducing, anti-anxiety/depression, and oral contraceptive therapies. Results: Baseline patient demographics were similar across treatment arms. Metabolism and nutrition disorders were reported most often in each treatment arm (placebo, 42.7%; deucravacitinib, 39.2%; apremilast, 38.4%), followed by vascular disorders (33.7%, 34.9%, and 31.8%, respectively). Hypertension was the most common baseline medical condition (placebo, 30.3%, deucravacitinib, 32.8%, and apremilast, 29.1%), with obesity, hyperlipidemia, type 2 diabetes mellitus, and seasonal allergies each reported in 10% to 12% of patients in at least one treatment arm. Antihypertensive and cardiovascular agents, lipid-reducing agents, and antidiabetic agents were the most commonly reported medications. Conclusion: The phase 3 POETYK PSO trials enrolled adults with moderate to severe plaque psoriasis with a range of comorbidities consistent with the real-world population of patients with psoriasis. Medication classes used by patients were consistent with the comorbidities reported at baseline in both trials.

Blood Pressure Control and Clinical Outcomes After Renal Denervation Through Irrigated Catheter Radiofrequency Ablation in Patients with Resistant Hypertension: A Case Series with Up to 10 Years of Follow-Up.

The long-term efficacy of renal denervation (RDN) has not been extensively documented. To describe the long-term follow-up of patients after RDN. We evaluated patients with resistant hypertension (RH) who underwent RDN with irrigated catheter from 2012 to 2014 at a single centre. Office blood pressure (BP) and 24-hour ambulatory BP were assessed. Clinical event (stroke, myocardial infarction, need for dialysis, or death from any cause), left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), and urine albumin-to-creatinine ratio (uACR) were evaluated. The analysis included 20 individuals (age 51 ± 10 years, 75% female, ambulatory systolic BP [SBP] 168 ± 22 mmHg, ambulatory diastolic BP [DBP] 101 ± 19 mmHg, taking 7 [IQR: 6-8] antihypertensive medications). The median follow-up period was 8.5 (IQR: 5.6-9.4) years. Mean (± SD) changes from baseline were: -47 ± 41 mmHg for office SBP, -25 ± 20 mmHg for office DBP, -29 ± 26 mmHg for ambulatory SBP, and -15 ± 16 mmHg for ambulatory DBP. The number of antihypertensive drugs markedly decreased one month after RDN and a gradual upward trend was observed over time. A clinical event occurred in 9 (45%) participants. LVMI decreased from 152 ± 37 to 120 ± 31g/m2 (p = 0.015), the eGFR declined from 88.9 ± 15.6 to 73.1 ± 24.2 mL/min/1.73 m2 (p = 0.034), and the uACR did not significantly change from baseline to follow-up. In this observational study of patients with uncontrolled RH, RDN with an irrigated catheter was associated with a sustained BP reduction for up to a decade. However, a potential waning efficacy was suggested by the increasing use of antihypertensive medications over time.