Antihypertensive Classes Research Articles

Comparative Pharmacotherapy of Hypertension

The purpose of the study. This study aims to review the practice of the utilization of antihypertensive drugs of various pharmacological groups within the condition of the therapeutic hospital in Ukrainian and Egyptian patients, adherence to treatment in patients with hypertension in Ukraine and Egypt. Materials and methods. A study of 120 patients who were treated for hypertension II stage in a therapeutic hospital in Ternopil and Cairo was conducted. All subjects completed a questionnaire that included personal, socio-demographic, and medical data. The number and type of hypotensive drugs or drug combinations were analyzed. Results and discussion. Regarding the pharmacotherapy of hypertension the use of β-blockers among Ukrainian participants did not differ from Egyptian. The use of calcium channel antagonists was a little bit higher among Egyptians than Ukrainians. Diuretics were used more often by Ukrainians than by Egyptians. The use of ACEI/ARBs surpassed the use of all other classes of antihypertensives among both groups. Whereas the ACEI/ARBs use among Egyptians was lower than Ukrainians. In this study we conducted a determination of compliance which was defined as an act of adhering to the regimen of care recommended by the clinician and persisting with it over time. The majority of Ukrainian and Egyptian patients with hypertension do not always perform the doctor's prescription. The reason for the unfull implementation of medical prescriptions with the same frequency was called deficiency of funds and forgetfulness. Near 80% of Ukrainian respondents are ready to complete the prescription with understanding, however, 14% of the patients stated that they were not always ready to fulfill the prescription, and the smallest part of patients did not think it was necessary to follow the regularity of treatment and treatment regimen. We noted no significant difference in the adherence to antihypertensive therapy between Ukrainian and Egyptian participants. Early discontinuation of treatment and suboptimal daily use of the prescribed regimens are the foremost common facets of poor adherence to treatment as well as non-adherence to antihypertensive therapy correlates with a better risk of cardiovascular events. Conclusion. ACEI/ARBs are the most commonly used group of antihypertensive drugs among Ukrainian and Egyptian patients. The majority of Ukrainian and Egyptian participants with hypertension do not always perform the doctor's prescription. Only 50% had an objective reason for insufficient compliance

Transcriptomic Response in the Heart and Kidney to Different Types of Antihypertensive Drug Administration.

Certain classes of antihypertensive drug may exert specific, blood pressure (BP)-independent protective effects on end-organ damages such as left ventricular hypertrophy, although the overall evidence has not been definitive in clinical trials. To unravel antihypertensive drug-induced gene expression changes that are potentially related to the amelioration of end-organ damages, we performed in vivo phenotypic evaluation and transcriptomic analysis on the heart and the kidney, with administration of antihypertensive drugs to two inbred strains (ie, hypertensive and normotensive) of rats. We chose 6 antihypertensive classes: enalapril (angiotensin-converting enzyme inhibitor), candesartan (angiotensin receptor blocker), hydrochlorothiazide (diuretics), amlodipine (calcium-channel blocker), carvedilol (vasodilating β-blocker), and hydralazine. In the tested rat strains, 4 of 6 drugs, including 2 renin-angiotensin system inhibitors, were effective for BP lowering, whereas the remaining 2 drugs were not. Besides BP lowering, there appeared to be some interdrug heterogeneity in phenotypic changes, such as suppressed body weight gain and body weight-adjusted heart weight reduction. For the transcriptomic response, a considerable number of genes showed prominent mRNA expression changes either in a BP-dependent or BP-independent manner with substantial diversity between the target organs. Noticeable changes of mRNA expression were induced particularly by renin-angiotensin system blockade, for example, for genes in the natriuretic peptide system (Nppb and Corin) in the heart and for those in the renin-angiotensin system/kallikrein-kinin system (Ren and rat Klk1 paralogs) and those related to calcium ion binding (Calb1 and Slc8a1) in the kidney. The research resources constructed here will help corroborate occasionally inconclusive evidence in clinical settings.

Antihypertensive drug classes and incident dementia: Findings from the PreDIVA observational extension study

AbstractBackgroundMidlife hypertension is a risk factor for all‐cause dementia. Treatment of hypertension with antihypertensive medication (AHM) may therefore be a promising strategy to delay or prevent dementia. Recent reports have suggested that AHM are associated with differential effects on dementia risk, due to class‐specific mechanisms. In this study, we assess the association between different AHM‐classes and incident dementia, using data from the preDIVA observational extension (POE) study.MethodAll participants who reported use of AHM at baseline were included in the analyses. We distinguished angiotensin‐converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta‐blockers, calcium channel blockers (CCBs), and diuretics. Data on incident dementia was collected during the randomised phase at 2, 4, 6‐8 and, after discontinuation of the intervention, 10‐12 years after baseline. Cox proportional hazards regression was used to study the association between use of different AHM‐classes, compared with use of any other AHM class, and incident dementia. A post‐hoc analysis was performed, dividing follow‐up time in two periods (preDIVA median follow‐up acting as cut‐off point) to account for the effect of time between exposure and dementia.Result1953 participants who reported AHM use at baseline were included, with a mean age of 74.5 (±2.5) and a mean systolic blood pressure of 156.4 mmHg (±21.5). After a median follow‐up of 10.4 years (IQR 6.7‐11.0), 228 (11.7%) participants had developed dementia. Adjusted hazard ratios (HR) for dementia were 1.07 (95%CI 0.80‐1.42) for ACE inhibitors, 0.75 (95%CI 0.53‐1.06) for ARBs, 1.00 (95%CI 0.77‐1.31) for beta‐blockers, 0.92 (95%CI 0.68‐1.24) for CCBs, and 1.02 (95%CI 0.78‐1.33) for diuretics. ARBs and CCBs were inversely associated with dementia during the first time period (HR 0.46, 95%CI 0.25‐0.84 and HR 0.62, 95%CI 0.38‐0.99 respectively), which was not apparent anymore during the second one.ConclusionDespite short‐term beneficial associations of CCBs and ARBs and a promising HR for ARBs also after longer follow‐up, associations between any AHM‐class and incident dementia were not convincing after complete follow‐up. These findings are possibly best explained by the long follow‐up in older participants with high mortality‐ and dementia rates, possibly attenuating AHM‐class effects on dementia incidence.

Effect of antihypertensive agents on metabolic syndrome: a systematic review and meta-analysis / Efeitos de antihipertensivos na síndrome metabólica: uma revisão sistemática e metanálise

Background: Metabolic syndrome (MetS) is a chronic disease defined by a set of genetic and environmental factors that determine high cardiovascular risk, being highly prevalent in hypertensive patients. Aim: To identify the efficacy of the association of antihypertensive drugs in hypertensive individuals with MetS. Methods: The systematic review searching the electronic databases Medline/PubMed, Lilacs, BVS and Periódicos Capes with articles published from 2010 to 2020. The registration number of this review at PROSPERO is CRD42021235614. Original articles and clinical randomized trials were included in present review. To calculate the meta-analytic effect measure was used the absolute difference between means using the random effects model with 95% confidence interval. Results: Eight articles were included in this review totaling data from 2,625 patients. In six papers was performed meta-analysis. The selected studies suggest that most combinations of antihypertensive drug classes reduced blood pressure to satisfactory values, and some combinations reduced markers of inflammation, improved lipid and glycemic parameters and reduced the risk of developing diabetes mellitus. The combination therapies between angiotensin receptor blockers (ARB) and calcium channel blockers (CCB), as well as, the combination between CCB and angiotensin converting enzyme inhibitors (ACEI) were well-tolerated and showed satisfactory results in hypertensive patients with metabolic syndrome. Conclusion: based on the results of the present study, we would like to suggest that further studies be carried out to assess the efficacy of the combination between irbesartan and manidipine (ARB and CCB), manidipine and Lisinopril (CCB and ACEI), and between enalapril and lercadipine (ACEI and CCB). These drugs have shown satisfactory results for use in hypertensive patients with MetS.

A Novel Hypertension Management Algorithm Guided by Hemodynamic Data

A Novel Hypertension Management Algorithm Guided by Hemodynamic Data

Self-Reported Antihypertensive Medication Class and Temporal Relationship to Treatment Guidelines.

The greater antihypertensive responses to initial therapy with calcium channel blockers (CCBs) or thiazide-type diuretics than renin-angiotensin system blockers as initial therapy in non-Hispanic Black (NHB) adults was recognized in the US High BP guidelines from 1988 to 2003. The 2014 Report from Panel Members Appointed to the Eighth Joint National Committee (2014 aJNC8 Report) and the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline were the first to recommend CCBs or thiazide-type diuretics rather than renin-angiotensin system blockers as initial therapy in NHB. We assessed the temporal relationship of these recommendations on self-reported CCB or thiazide-type diuretics monotherapy by NHB and NHW adults with hypertension absent compelling indications for β-blockers or renin-angiotensin system blockers in National Health and Nutrition Examination Surveys 2015 to 2018 versus 2007 to 2012 (after versus before 2014 aJNC8 Report). CCB or thiazide-type diuretics monotherapy was unchanged in NHW adults (17.1% versus 18.1%, P=0.711) and insignificantly higher after 2014 among NHB adults (43.7% versus 38.2%, P=0.204), although CCB monotherapy increased (29.5% versus 21.0%, P=0.021) and renin-angiotensin system blocker monotherapy fell (44.5% versus 31.0%, P=0.008). Although evidence-based CCB monotherapy increased among NHB adults in 2015 to 2018, hypertension control declined as untreated hypertension and monotherapy increased. While a gap between recommended and actual monotherapy persists, evidence-based monotherapy appears insufficient to improve hypertension control in NHB adults, especially given evidence for worsening therapeutic inertia. Initiating treatment with single-pill combinations and timely therapeutic intensification when required to control hypertension are evidence-based, race-neutral options for improving hypertension control among NHB adults.

Abstract 14094: Characterizing Dual Combination Therapy Use In Treatment Escalation Of Hypertension: Real-world Evidence From Multinational Cohorts

Introduction: Over one billion adults have hypertension globally, of whom 70% cannot achieve hypertension control with monotherapy. Data are lacking on patterns of dual combination therapies prescribed to patients who escalate from monotherapy. Methods: We described dual combination therapy utilization using eleven electronic health record databases covering 118 million patients across eight countries. We identified patients who newly initiated dual combination of four most commonly used antihypertensive drug classes (angiotensin-converting enzyme inhibitor [ACEi] or angiotensin receptor blocker [ARB]; calcium channel blocker [CCB]; beta-blocker; and thiazide or thiazide-like diuretic) after being on monotherapy. Results: We identified 980,648 patients with hypertension initiating dual combination therapy with antihypertensive agents after being on monotherapy: 12,541 from Australia, 6,980 from South Korea, 2,096 from Singapore, 7,008 from China, 16,663 from Taiwan, 103,994 from France, 76,082 from Italy, and 754,137 from the United States (US). Significant variations in treatment utilization existed across countries and patient subgroups. In Australia and Singapore, starting an ACEi/ARB monotherapy followed by a CCB was most common while in South Korea, China and Taiwan, starting a CCB monotherapy followed by an ACEi/ARB was most common. In Italy, France, and the US, sequential use of an ACEi/ARB monotherapy followed by a diuretic was most common. Younger patients were more likely to be prescribed ACEi/ARB followed by either a CCB or a diuretic compared with older patients. Women were more likely to be prescribed diuretics then an ACEi/ARB or a CCB compared with men. Conclusion: A large variation in the transition between monotherapy and dual combination therapy for hypertension was observed across countries. These results highlight the need for future research to identify which dual combination therapy is most effective for which patients.

Clinicians' prescribing pattern, rate of patients' medication adherence and its determinants among adult hypertensive patients at Jimma University Medical Center: Prospective cohort study.

Many studies conducted in the past focused on patients' sociodemographic factors and medical profiles to identify the determinants of suboptimal blood pressure control. However, prescribing patterns and clinicians' adherence to guidelines are also important factors affecting the rate of blood pressure control. Therefore, this study aimed to determine clinicians' prescribing patterns, patients' medication adherence, and its determinants among hypertensive patients at Jimma University Medical Center. A general prospective cohort study was conducted among hypertensive patients who had regular follow-up at Jimma university ambulatory cardiac clinic from March 20, 2018, to June 20, 2018. Patients' specific data was collected with a face-to-face interview and from their medical charts. Clinicians' related data were collected through a self-administered questionnaire. Data were analyzed using SPSS version 21.0. Bivariate and multivariable logistic regression analyses were done to identify key independent variables influencing patients' adherence. P-Values of less than 0.05 were considered statically significant. From the total of 416 patients, 237(57.0%) of them were males with a mean age of 56.50 ± 11.96 years. Angiotensin-converting enzyme inhibitors were the most frequently prescribed class of antihypertensives, accounting for 261(63.7%) prescriptions. Combination therapy was used by the majority of patients, with 275 (66.1%) patients receiving two or more antihypertensive drugs. Patients' medication adherence was 46.6%, while clinicians' guideline adherence was 44.2%. Patients with merchant occupation (P = 0.020), physical inactivity (P = 0.033), and diabetes mellitus co-morbidity (P = 0.008) were significantly associated with a higher rate of medication non-adherence. The rate of medication adherence was poor among hypertensive patients. Physicians were not-adherent to standard treatment guideline. The most commonly prescribed class of drugs were angiotensin-converting enzyme inhibitors. Effective education should be given to patients to improve medication adherence. Prescribers should be trained on treatment guidelines regularly to keep them up-to-date with current trends of hypertension treatment and for better treatment outcomes.

Association between MR-proADM concentration and treatment intensity of antihypertensive agents in chronic kidney disease patients with insufficient blood pressure control

Response to antihypertensive drugs in patients with chronic kidney disease (CKD) has great interindividual variability. Adrenomedullin (ADM) is produced abundantly in hypertension, but clearance is very rapid. Mid-regional proADM (MR-proADM) produced from an ADM precursor is considered a surrogate biomarker for quantification of ADM. We investigated the association of MR-proADM with antihypertensive resistance in CKD patients with poor blood pressure (BP) control. This cross-sectional study analyzed 33 CKD patients with poor BP control defined as failure to achieve target BP despite at least two classes of antihypertensive drugs. Treatment intensity score was calculated to facilitate comparability of antihypertensive regimens across subjects taking different drugs. Plasma MR-proADM concentration was measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Plasma MR-proADM concentration correlated with estimated glomerular filtration rate (eGFR) (r = − 0.777, p < 0.001). Treatment intensity score correlated positively with plasma MR-proADM concentration (r = 0.355, p = 0.043), and the correlation was further enhanced after correction by weight (r = 0.538, p = 0.001). Single and multiple regression analysis identified MR-proADM concentration (p = 0.005) as independently associated with weight-corrected treatment intensity score. MR-proADM may be useful as a biomarker to determine the therapeutic intensity of antihypertensive drugs in CKD patients with poor BP control.

Antihypertensive Drug Use and the Risk of Depression: A Systematic Review and Network Meta-analysis.

Background: Although numerous cohort studies have reported an association between antihypertensives use and depression, the exact effect of antihypertensives on depression remains unclear. Objective: To clarify the association between antihypertensives use and risk of depression. Methods: We retrieved relevant literature using PubMed database until August 30, 2021. Four main classes of antihypertensives, thus, angiotensin antagonists, beta blockers, calcium channel blockers and diuretics were studied. The incidence of depression was pooled based on a single drug category. Network meta-analyses were conducted to comprehensively assess the effects of the four classes of antihypertensives on the risk of depression. Results: A total of nine out of 9,557 studies involving 414,873 subjects were retrieved. The pooled results showed a positive association between the use of calcium channel blockers and symptoms of depression [odds ratio (OR): 1.09, 95% confidence interval (CI):1.06–1.13], while use of the angiotensin antagonists, beta blockers and diuretics was not associated with risk of depression. Subgroup analysis suggested a significant relationship between beta blockers usage and risk of depression in cohort studies (OR:1.21, 95% CI: 1.16–1.26). The results of network meta-analysis indicated that all other three classes of drugs increased the risk of depression: angiotensin antagonists (OR: 1.30, 95% CI: 1.04–1.63), beta blockers (OR: 1.53, 95% CI: 1.22–1.91), and calcium channel blockers (OR: 1.40, 95% CI: 1.12–1.75), compared with diuretics. Conclusion: In conclusion, our results indicate that the use of angiotensin antagonists, beta blockers and calcium channel blockers are potential risk factors of depression.

Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis

SummaryBackgroundBlood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials.MethodsWe performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists’ Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of follow-up in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons.Findings145 939 participants (88 500 [60·6%] men and 57 429 [39·4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4·5 years (IQR 2·0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0·89 [95% CI 0·84–0·95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0·84 [95% 0·76–0·93]) and angiotensin II receptor blockers (RR 0·84 [0·76–0·92]) reduced the risk of new-onset type 2 diabetes; however, the use of β blockers (RR 1·48 [1·27–1·72]) and thiazide diuretics (RR 1·20 [1·07–1·35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1·02 [0·92–1·13]).InterpretationBlood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual's clinical risk of diabetes.FundingBritish Heart Foundation, National Institute for Health Research, and Oxford Martin School.

Blood pressure lowering in the prevention of type 2 diabetes

Hypertension increases the risk for many conditions, including ischaemic heart disease, heart failure, stroke, and kidney disease. 1 Thomopoulos C Parati G Zanchetti A Effects of blood pressure lowering on outcome incidence in hypertension. 1. Overview, meta-analyses, and meta-regression analyses of randomized trials. J Hypertens. 2014; 32: 2285-2295 Crossref PubMed Scopus (207) Google Scholar Hypertension frequently coexists with diabetes as obesity increases the risk of developing both conditions. In patients with diabetes, two-thirds also have hypertension. 2 Centers for Disease Control and PreventionNational Diabetes Statistics Report, 2020. Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, GA2020 Google Scholar , 3 Chow CK Teo KK Rangarajan S et al. Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. JAMA. 2013; 310: 959-968 Crossref PubMed Scopus (1143) Google Scholar In the USA, four of the top ten causes of death are associated with hypertension (ie, heart disease, stroke, diabetes, and renal disease). 4 Ahmad FB Anderson RN The leading causes of death in the US for 2020. JAMA. 2021; 325: 1829-1830 Crossref PubMed Scopus (247) Google Scholar Thus, strategies that reduce comorbidities associated with hypertension are important. Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysisBlood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual's clinical risk of diabetes. Full-Text PDF Open Access

Antihypertensive drug class in combination with lipid lowering treatment for primary prevention of cardiovascular disease in the elderly

BackgroundAntihypertensives and lipid-lowering therapy (LLT) are often used concurrently. ObjectivesTo determine whether there was a difference in clinical outcomes when older patients with LLT were prescribed angiotensin-converting-enzyme-inhibitors (ACE-Is) compared with diuretics. MethodsThis analysis included 648 LLT older users free of cardiovascular disease (CVD) from a trial comparing ACE-I versus diuretic-based therapy. Comparisons were made between LLT+ACE-I (n = 335) and LLT+diuretic groups (n = 313) using multivariable Cox proportional-hazard models. Primary endpoints were all-cause and CVD mortality (in-trial [4.1-year]+post-trial [6.9-year]) and secondary endpoints (in-trial) were the composite of all-cause mortality and first CVD events and its components, CVD mortality and incident diabetes. ResultsThere were no significant differences between the two groups for the primary endpoints over the in-trial plus post-trial follow-up, nor was there a difference for any secondary outcomes over the in-trial follow-up. ConclusionsThe LLT+ACE-I and LLT+diuretic combinations showed similar effects in CVD-free older individuals. Randomised trials are needed to provide conclusive evidence.

Current Approaches to Arterial Hypertension Management in Children and Adolescents: Clinical Guidelines Review

The prevalence of arterial hypertension (AH) in children and adolescents is increasing, thus it is crucial and topical to make pediatricians familiar with modern approaches in drug and drug-free therapy for AH. The aim of this review was to provide the overview of international and Russian guidelines for the AH treatment. We have searched the following keywords in PubMed: guidelines, arterial hypertension treatment, guidelines of management, pediatric hypertension. Reviews, clinical guidelines, and original articles published from 2010 to 2020 were analyzed. Detailed description of AH management in children and adolescents is presented. Approaches to drug-free correction of increased blood pressure (BP) are discussed in detail, indications for antihypertensive therapy are described, characteristics of the main classes of antihypertensive drugs are given (indications, contraindications, and possible side effects). Principles of refractory AH management and antihypertensive drugs combinations are also described.

Effect of dihydropyridine calcium channel blockers on blood pressure variability in the SPRINT trial: a treatment effects approach.

Increased visit-to-visit blood pressure variability (vvBPV) has negative effects on multiple organ systems. Prior research has suggested that dihydropyridine calcium channel blockers (CCB) may reduce vvBPV, which we attempted to verify in a high-quality dataset with robust statistical methodology. We performed a post hoc analysis of the SPRINT trial and included participants who were on a dihydropyridine CCB either 0 or 100% of follow-up study visits. The primary outcome was vvBPV, defined as residual standard deviation (rSD) of SBP from month 6 until study completion. We estimated the average treatment effect of the treated (ATET) after augmented inverse-probability-weighting (AIPW) matching. Of the 9361 participants enrolled in SPRINT, we included 5020, of whom 1959 were on a dihydropyridine CCB and 3061 were not; mean age was 67.4 ± 9.2 years, 34.5% were men, 65.9% were white, 49.4% were randomized to intensive blood pressure control, and the rSD was 10.1 ± 4.0 mmHg. Amlodipine represented greater than 95% of dihydropyridine CCB use. After AIPW matching of demographics and other antihypertensive medications, the ATET estimation for participants on a dihydropyridine CCB was an rSD that was 2.05 mmHg lower (95% CI -3.19 to -0.91). We did not find that other antihypertensive medications classes decreased vvBPV, and several increased it. In the SPRINT trial, consistent use of a dihydropyridine CCB was associated with a 2 mmHg reduction in vvBPV. The implication of this hypothesis-generating finding in a high-quality dataset is that future trials to reduce vvBPV could consider using dihydropyridine CCBs.

Arterial hypertension: modern advances in metabolomics

Early diagnosis and effective pharmacotherapy of arterial hypertension are urgent problems, a significant contribution to the solution of which can be made by metabolomics. The etiology of hypertension remains unknown for the majority of patients with high blood pressure; the diagnosis for 90% is defined as essential (primary) hypertension. This population is characterized by disturbance of the metabolic pathways of lipids, glucose, biogenic amines and amino acids, which may manifest with hyperlipidemia, hyperglycemia, and insulin resistance with the possible subsequent development of type II diabetes mellitus. The study of the metabolomic signature can provide a clue to the identification of biomarkers of hypertension and contribute to the effective development of preclinical diagnosis and identification of risk groups, as well as a more complete understanding of the etiological and pathogenetic mechanisms of increased blood pressure. Published studies indicate the existence of metabolome characteristic of hypertensive patients, distinguishing them from normotensive subjects. The most typical are changes involving amino acids, polyunsaturated fatty acids, carnitines, phosphatidylcholines, and acylglycerols.The variability of the response to antihypertensive therapy does not allow achieving effective control of blood pressure in a significant proportion of patients. The peculiarities of changes in the metabolome under the use of various pharmacological groups can be used to identify metabolite markers of the response to the main classes of antihypertensive drugs, as well as markers of the development of side effects of drug therapy. Thus, individualization of the pharmacotherapeutic approach based on pharmacometabolomics can significantly increase the efficacy and safety of antihypertensive therapy.This review aims to study the main groups of metabolites identified in published trials as predictors of the development of hypertension, as well as metabolite markers of response to antihypertensive therapy.

Calcium channel blockers versus other classes of drugs for hypertension.

This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the effect of CCBs on the prevention of cardiovascular events, as compared with other antihypertensive drug classes, is still debated. To determine whether CCBs used as first-line therapy for hypertension are different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events. For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to 1 September 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 1), Ovid MEDLINE, Ovid Embase, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted the authors of relevant papers regarding further published and unpublished work and checked the references of published studies to identify additional trials. The searches had no language restrictions. Randomised controlled trials comparing first-line CCBs with other antihypertensive classes, with at least 100 randomised hypertensive participants and a follow-up of at least two years. Three review authors independently selected the included trials, evaluated the risk of bias, and entered the data for analysis. Any disagreements were resolved through discussion. We contacted study authors for additional information. This update contains five new trials. We included a total of 23 RCTs (18 dihydropyridines, 4 non-dihydropyridines, 1 not specified) with 153,849 participants with hypertension. All-cause mortality was not different between first-line CCBs and any other antihypertensive classes. As compared to diuretics, CCBs probably increased major cardiovascular events (risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.09, P = 0.03) and increased congestive heart failure events (RR 1.37, 95% CI 1.25 to 1.51, moderate-certainty evidence). As compared to beta-blockers, CCBs reduced the following outcomes: major cardiovascular events (RR 0.84, 95% CI 0.77 to 0.92), stroke (RR 0.77, 95% CI 0.67 to 0.88, moderate-certainty evidence), and cardiovascular mortality (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence). As compared to angiotensin-converting enzyme (ACE) inhibitors, CCBs reduced stroke (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence) and increased congestive heart failure (RR 1.16, 95% CI 1.06 to 1.28, low-certainty evidence). As compared to angiotensin receptor blockers (ARBs), CCBs reduced myocardial infarction (RR 0.82, 95% CI 0.72 to 0.94, moderate-certainty evidence) and increased congestive heart failure (RR 1.20, 95% CI 1.06 to 1.36, low-certainty evidence). For the treatment of hypertension, there is moderate certainty evidence that diuretics reduce major cardiovascular events and congestive heart failure more than CCBs. There is low to moderate certainty evidence that CCBs probably reduce major cardiovascular events more than beta-blockers. There is low to moderate certainty evidence that CCBs reduced stroke when compared to angiotensin-converting enzyme (ACE) inhibitors and reduced myocardial infarction when compared to angiotensin receptor blockers (ARBs), but increased congestive heart failure when compared to ACE inhibitors and ARBs. Many of the differences found in the current review are not robust, and further trials might change the conclusions. More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.

Elevated blood pressure, antihypertensive medications and bone health in the population: revisiting old hypotheses and exploring future research directions

Blood pressure and bone metabolism appear to share commonalities in their physiologic regulation. Specific antihypertensive drug classes may also influence bone mineral density. However, current evidence from existing observational studies and randomised trials is insufficient to establish causal associations for blood pressure and use of blood pressure–lowering drugs with bone health outcomes, particularly with the risks of osteoporosis and fractures. The availability and access to relevant large-scale biomedical data sources as well as developments in study designs and analytical approaches provide opportunities to examine the nature of the association between blood pressure and bone health more reliably and in greater detail than has ever been possible. It is unlikely that a single source of data or study design can provide a definitive answer. However, with appropriate considerations of the strengths and limitations of the different data sources and analytical techniques, we should be able to advance our understanding of the role of raised blood pressure and its drug treatment on the risks of low bone mineral density and fractures. As elevated blood pressure is highly prevalent and blood pressure–lowering drugs are widely prescribed, even small effects of these exposures on bone health outcomes could be important at a population level.

Biological effects of the antihypertensive losartan under different ocean acidification scenarios

Since the last decade, several studies have reported the presence and effects of pharmaceutical residues in the marine environment, especially those of the antihypertensive class, such as losartan. However, there is little knowledge about the physiological effects of losartan in marine invertebrates regarding its behavior under possible coastal ocean acidification scenarios. The objective of this study was to evaluate biological effects on marine organisms at different levels of the biological organization caused by the compound losartan in water and sediment under coastal ocean acidification scenarios. Water and sediment samples were collected at five sites around the Santos Submarine Sewage outfall (SSO) and two sites around the Guarujá Submarine Sewage Outfall (GSO). Losartan was found in concentrations ranging from <LOD to 7.63 ng/L in water and from <LOQ to 3.10 ng/g in sediments. Statistical analysis showed interactive effects pH and losartan on the toxicity results. The water toxicity test with Echinometra lucunter embryos/larvae showed LOECs 50–100 mg/L, with values decreasing as the pH decreased. In the sediment assays, LOEC value for sea urchin embryo-larval development was 1.0 μg/g for all tested pHs. Regarding the lysosomal membrane stability assays with adult bivalves, a LOEC of 3000 ng/L was found for Perna perna in water exposure (both at pH 8.0 and 7.6). Effects for Mytella guyanensis were observed at environmentally relevant concentrations in sediment (LOEC = 3 ng/g at pH 8.0 and 7.6). This study demonstrated that coastal ocean acidification by itself causes effects on marine invertebrates, but can also increase the negative effects of losartan in waterborne exposure. There is a need to deepen the studies on the ecotoxicity of pharmaceutical residues and acidification of the marine environment.

OUTCOMES OF PATIENTS WITH COVID-19 ON ANTIHYPERTENSIVE MEDICATIONS IN SOUTHERN PENNSYLVANIA

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: The controversy surrounding the association of ACE inhibitor (ACEi) use in the COVID-19 pandemic has been well documented. Since then, studies have been published refuting the findings. While there was a recent study in France on hypertensive patients on one of ACEi, angiotensin II receptor blocker (ARB) or calcium channel blocker (CCB), we performed a retrospective study reviewing the outcomes (i.e. admissions, readmission and mortality) associated with COVID-19 patients and their use of anti-hypertensive medications (anti-HTNs), specifically ACEi/ARB, thiazides, beta blocker (BB) and CCB, to look at the outcomes associated with their use, regardless of their roles in anti-hypertensive management. METHODS: We performed a retrospective study on patients with a positive COVID-19 RT-PCR test since January 2019. 606 adult patients were randomly selected. Data on demographics, co-morbidities, admission status, length of stay, types of anti-hypertensives and outcomes were collected and reviewed. RESULTS: Our study demonstrated the use of ACEi (24.1%) and thiazides (17.5%) had a reduced rate of admission when compared to patients on BB (32.3%) or CCB (32.4%). It should be noted thiazides were not as widely used (n = 63) in our population. Thus, it was not possible to comment on whether its use had a role in preventing hospitalization. Among the agents, ACEi is widely used for a multitude of diseases. As a result, it is often a first line agent employed by many, which was consistent with the data (n = 294) collected in this study. Interestingly, when assessing readmission rates, ACEi had the lowest percentage (8.1%;6/74) among the classes (BB 13.3%;8/60, CCB 18.4%;7/38, Thiazide 15.4%;2/13). Its judicious use and lower rates of admission and readmission were perhaps a compliment to the fine work by the physicians involved in their care.For mortality, there was a minimal percentage difference across the classes (ACEi 25.7%, BB 23.3%, CCB 23.7%, thiazides 23.1%). While there was a difference in number of patients across all four medications, the similar mortality suggested the co-morbidities, rather than the medications, may have a stronger influence on the outcomes in these patients. CONCLUSIONS: Our study demonstrated ACEi had a reduced rate of admission and the lowest rate of readmission compared to patients on BB or CCB. There was no difference in mortality across all four anti-hypertensive classes. We believe studies assessing co-morbidities while controlling for anti-hypertensive use could be beneficial in further our understanding in predicting outcomes of COVID-19 patients. CLINICAL IMPLICATIONS: ACEi use did not appear to have higher admission rates than other anti-hypertensives. Its use resulted in the lowest re-admission rates. The use of specific anti-hypertensive class had no bearing on mortality rates of COVID-19 patients. DISCLOSURES: No relevant relationships by Ali AKRAM, source=Web Response No relevant relationships by Vernon Chan, source=Web Response No relevant relationships by Dana Daoud, source=Web Response No relevant relationships by Olufunmilayo Folaranmi, source=Web Response No relevant relationships by Christopher Hemsley, source=Web Response No relevant relationships by Hafiza Wajeeha Javaid, source=Web Response No relevant relationships by Sarah Maurice, source=Web Response No relevant relationships by Junaid mir, source=Web Response No relevant relationships by Aisha Parihar, source=Web Response No relevant relationships by Britney Plotnick, source=Web Response No relevant relationships by Jayaram Thimmapuram, source=Web Response