Therapy For Arterial Hypertension Research Articles

Safety and efficacy of rodatristat ethyl for the treatment of pulmonary arterial hypertension (ELEVATE-2): a dose-ranging, randomised, multicentre, phase 2b trial

The role of serotonin in pulmonary arterial hypertension has been extensively studied in recent decades, with preclinical data strongly indicating involvement in disease pathogenesis; however, clinical studies have yielded mixed results. ELEVATE-2 was a phase 2b dose-ranging, randomised, double-blind, placebo-controlled, multicentre trial investigating rodatristat ethyl as a treatment for patients with pulmonary arterial hypertension. The study was conducted at 64 sites across 16 countries in Europe and North America. Eligible participants were aged 18 years or older, had pulmonary arterial hypertension with WHO functional class II or III symptom severity, and had received a stable dose and regimen of one or more pulmonary arterial hypertension treatments for at least 12 weeks. Participants were randomly assigned 1:1:1 to receive two placebo tablets, one placebo and one rodatristat ethyl 300 mg tablet, or two rodatristat ethyl 300 mg tablets twice daily using an interactive response system. Participants, investigators, site personnel, and sponsors were masked to treatment allocation. Participants who completed the 24 week treatment period were invited to continue in an open-label extension. The primary endpoint was percent change in pulmonary vascular resistance (PVR) from baseline to week 24. Primary efficacy analyses were conducted on the intention-to-treat population and analyses of harms were conducted in the safety population, which included all patients who received any amount of the study drug. This trial is registered with ClinicalTrials.gov, NCT04712669, and is now complete. Between March 18, 2021 and Dec 13, 2022, 108 participants were enrolled and randomly assigned. 36 participants received placebo, 36 received rodatristat ethyl 300 mg, and 36 received rodatristat ethyl 600 mg twice daily. Overall, 85 (79%) of participants were female and 23 (21%) were male. The mean age was 52·8 years (SD 14·7) in the full analysis set. In the open-label extension phase, 62 (82%) of participants were female and 14 (18%) were male, and the mean age was 52·8 years (SD 14·7); this phase was terminated following sponsor review of unmasked main study results. Least-squares mean percent change in PVR from baseline to week 24 favoured placebo and was 5·8% (SE 18·1) for the placebo group, 63·1% (18·5) for the rodatristat ethyl 300 mg group, and 64·2% (18·0) for the rodatristat ethyl 600 mg group. Treatment-emergent adverse events (TEAE) were reported for 29 (81%) patients in the placebo group, 33 (92%) patients in the rodatristat ethyl 300 mg group, and all 36 (100%) patients in the rodatristat ethyl 600 mg group. TEAE leading to study discontinuation were reported for three (8%) patients in the placebo group, four (11%) patients in the rodatristat ethyl 300 mg group, and four (11%) in the rodatristat ethyl 600 mg group. There was one (3%) TEAE leading to death in the rodatristat ethyl 300 mg group. Our results indicate that reducing peripheral serotonin concentrations via rodatristat ethyl has a negative effect on pulmonary haemodynamics and cardiac function in patients with pulmonary arterial hypertension. This finding suggests that manipulating this pathway might not be a suitable option for pulmonary arterial hypertension therapy. Enzyvant Therapeutics (now Sumitomo Pharma America).

Trustworthiness, Value, Danger, and Readability of ChatGPT-Generated Responses to Health Questions Related to Pulmonary Arterial Hypertension.

To enhance outcomes for patients with pulmonary arterial hypertension (PAH), comprehensive and individualized therapy is needed. A large language model called Generative Pre-trained Transformer (ChatGPT) has the ability to provide expert yet patient-friendly care. We wanted to determine how well ChatGPT could accurately and consistently respond to inquiries on knowledge and management for PAH. When 20 PAH patients were diagnosed, they were asked what concerns they had about PAH and what they had researched online.In the evaluation, it was determined that patients frequently searched the Internet for answers to eight queries. These eight queries were posed to ChatGPT, and their responses were recorded. Ten experts in the field of PAH assessed the trustworthiness, value, and hazard of the answers generated by the ChatGPT. According to evaluations conducted by experts, the ChatGPT-generated responses were deemed trustworthy with an average score of 8.4 (7.7-9.2) and valuable with an average score of 7.9 (7.4-8.2). Based on the statistical analysis, it can be inferred that most professionals believed that the utilization of prompts provided by ChatGPT did not present a substantial risk, with a mean of 2.1 (1.7-2.5).The answers were assessed for readability using two different indicators, namely the Flesch-Kincaid Grade Level (FKGL) and the Simple Measure of Gobbledygook (SMOG). The average FKGL value was determined to be 13.52 ± 2.40, indicating a "difficult" level of readability. ChatGPT provides reliable PAH-related information, but it is important to seek professional medical advice before making any decisions regarding PAH. ChatGPT can only provide general information and support, but a qualified healthcare provider can offer tailored recommendations.

Adherence to drug therapy in systemic arterial hypertension in a Family Health Unit

Adherence to drug therapy in systemic arterial hypertension in a Family Health Unit

Adherence to drug therapy in systemic arterial hypertension in a Family Health Unit

Adherence to drug therapy in systemic arterial hypertension in a Family Health Unit

Pulmonary hypertension associated with left heart disease.

Left heart disease (LHD) is the most common cause of pulmonary hypertension (PH), which may be classified further as isolated post-capillary (ipcPH) or combined post- and pre-capillary PH (cpcPH). The 7th World Symposium on Pulmonary Hypertension PH-LHD task force reviewed newly reported randomised clinical trials and contemplated novel opportunities for improving outcome. Results from major randomised clinical trials reinforced prior recommendations against the use of pulmonary arterial hypertension therapy in PH-LHD outside of clinical trials, and suggested possible harm. Greater focus on phenotyping was viewed as one general strategy by which to ultimately improve clinical outcomes. This is potentially achievable by individualising ipcPH versus cpcPH diagnosis for patients with pulmonary arterial wedge pressure within a diagnostic grey zone (12-18 mmHg), and through a newly developed PH-LHD staging system. In this model, PH accompanies LHD across four stages (A=at risk, B=structural heart disease, C=symptomatic heart disease, D=advanced), with each stage characterised by progression in clinical characteristics, haemodynamics and potential therapeutic strategies. Along these lines, the task force proposed disaggregating PH-LHD to emphasise specific subtypes for which PH prevalence, pathophysiology and treatment are unique. This includes re-interpreting mitral and aortic valve stenosis through a contemporary lens, and focusing on PH within the hypertrophic cardiomyopathy and amyloid cardiomyopathy clinical spectra. Furthermore, appreciating LHD in the profile of PH patients with chronic lung disease and chronic thromboembolic pulmonary disease is essential. However, engaging LHD patients in clinical research more broadly is likely to require novel methodologies such as pragmatic trials and may benefit from next-generation analytics to interpret results.

Comparative Effectiveness of Sotatercept and Approved Add-On Pulmonary Arterial Hypertension Therapies: A Systematic Review and Network Meta-Analysis.

Background: There are no direct comparisons of sotatercept to add-on therapies approved for pulmonary arterial hypertension (PAH). Objective: This study aimed to compare the efficacy and safety of add-on sotatercept versus other add-on therapies using a network meta-analysis. Data Sources: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov until April 15, 2023, for randomized trials involving patients with PAH who were treated with add-on sotatercept or other add-on PAH therapies. Data Extraction: Data extraction and risk-of-bias assessments were performed independently and in duplicate using the Cochrane RoB 2.0 tool. We performed a frequentist random-effects network meta-analysis using the restricted maximum-likelihood estimator and assessed the certainty of evidence using the GRADE (grading of recommendations assessment development, and evaluation) approach. Synthesis: Our search found 18 trials (5,777 patients) eligible for analysis. Sotatercept reduces clinical worsening as compared with placebo (relative risk [RR], 0.21; 95% confidence interval [CI] = 0.11-0.41; with high certainty). Sotatercept probably reduces clinical worsening more, compared with add-on endothelin receptor antagonists (RR, 0.28; 95% CI = 0.14-0.55), inhaled prostanoid (RR, 40.21; 95% CI = 0.07-0.67), and prostanoid taken orally (RR, 0.32; 95% CI = 0.16-0.67; all with moderate certainty). Sotatercept probably improves 6-minute-walk distance compared with placebo (mean difference [MD], 36.89 m; 95% CI = 25.26-48.51). Although sotatercept probably improves 6-minute-walk distance more than add-on endothelin receptor antagonists (MD, 18.38 m; 95% CI = 5.92-30.84) and prostanoid taken orally (MD, 25.66 m; 95% CI = 13.71-37.61), it did not exceed the minimal clinically important difference of 33 m (both with moderate certainty). Conclusions: Sotatercept is an effective add-on therapy for PAH, likely superior to many approved add-on PAH therapies in reducing clinical worsening.

Approaches to therapy Amlodipine/Indapamide/Perindopril therapy of high arterial hypertension in ischemic heart disease patients with chronic kidney disease stage 1-3 after coronary stenting

Introduction: Acute coronary syndrome, chronic forms of ischemic heart disease (IHD) and postinfarction cardiosclerosis are the main causes of morbidity and mortality in the world, including Russia. In the XXI century, there is an increase in comorbid pathology, especially in the combination of IHD with arterial hypertension, diabetes, chronic obstructive pulmonary disease and chronic kidney disease. Patients with IHD and chronic kidney disease have a higher incidence of coronary events and complications. The frequency of coronary events and complications indicates the need to improve the diagnosis and treatment of this group of patients. diagnosis and treatment of this group of patients. The aim of the study was to analyze the dynamics of vascular stiffness, pulmonary hypertension (PH), diastolic heart dysfunction and endothelial dysfunction indices in patients with different variants of ischemic heart disease combined with chronic kidney disease (CKD) stage 1-3 using complex therapy of combined hypotensive drug Amlodipine/Indapamide/Perindopril three months after coronary stenting and to compare them with the group of patients on conservative therapy only. Materials and Methods: 85 patients with different forms of IHD, arterial hypertension (AH) on the background of CKD 1-3 stages, as well as data of 42 patients with IHD, AH without renal pathology were analyzed. The first group – IHD, postinfarction cardiosclerosis, CKD stage 1-3 (33 patients); the second group – acute coronary syndrome with ST-segment elevation, Myocardial infarction (MI) (30 patients); the third group – ACS without ST-segment elevation, Unstable angina (UA) (22 patients). Results: The highest indices of vascular stiffness (Pulse wave velocity (PWV), Augmentation index (AI), CAVI, Central Systolic Blood Pressure (SBPao), central arterial pulse pressure (PP)) were registered in combination of ACS with ST-segment elevation and CKD 1-3 stages. These indices are markers of IHD progression in these patients; they also have increased pulmonary hypertension and diastolic dysfunction of the heart, endothelial dysfunction with vasodilation insufficiency in 88% of cases, which even without hemodynamically significant coronary artery stenoses according to coronary CT angiography data leads to the development of ACS with ST-segment elevation and ACS without ST-segment elevation with MI. Amlodipine/Indapamide/Perindopril was prescribed to all patients due to high arterial hypertension on admission against the background of basic therapy of IHD and coronary stenting. Coronary CT angiography in patients with comorbid renal pathology does not lead to aggravation of chronic kidney disease after 3 months, on the contrary; in this group of patients the most pronounced decrease of arterial stiffness (AS), AI, SBPao, PP with elevation of glomerular filtration rate (GFR) and decrease of creatinine in blood occurs in comparison with the group of patients who did not undergo coronary stenting, they were only on conservative therapy. Conclusion: Prescription of three component drug Amlodipine/Indapamide/Perindopril on the background of baseline therapy especially in combination with surgical vascularization of the heart is justified.

Renal denervation in secondary arterial hypertension therapy: clinical case

Introduction. Renovascular hypertension is one of the most severe types of hypertension in terms of the choice of treatment strategy. Recent studies have not provided a clear answer to the question of which treatment approach (conservative or surgical) is most appropriate for these patients.Brief description. The presented case describes a female patient with a longterm uncontrolled hypertension, whose examination revealed bilateral renal artery stenosis. Considering the debatable clinical effectiveness of revascularization of renal artery stenosis, the patient underwent distal renal artery denervation using multielectrode catheters. A decrease in blood pressure was shown. Follow-up of the patient demonstrated stable antihypertensive effect of the procedure, as well as its safety in case of impaired renal function.Discussion. This clinical demonstrates the third way in the treatment of patients with renal arteries stenosis and resistant hypertension — renal sympathetic denervation. This method requires a separate controlled study with individuals with renal dysfunction, including renovascular origin.

US commercial health plan coverage dynamics in pulmonary arterial hypertension therapies.

Health plan coverage is central to patient access to care, especially for rare, chronic diseases. For specialty drugs, coverage varies, resulting in barriers to access. Pulmonary arterial hypertension (PAH) is a rare, progressive, and fatal disease. Guidelines suggest starting or rapidly escalating to combination therapy with drugs of differing classes (phosphodiesterase 5 inhibitors [PDE5is], soluble guanylate cyclase stimulators [sGC stimulators], endothelin receptor antagonists [ERAs], and prostacyclin pathway agents [PPAs]). To assess the variation in commercial health plan coverage for PAH treatments and how coverage has evolved. To examine the frequency of coverage updates and evidence cited in plan policies. We used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes publicly available specialty drug coverage policies. Overall, and at the drug and treatment class level, we identified plan-imposed coverage restrictions beyond the drug's US Food and Drug Administration label, including step therapy protocols, clinical restrictions (eg, disease severity), and prescriber specialty requirements. We analyzed variation in coverage restrictiveness and how coverage has changed over time. We determined how often plans update their policies. Finally, we categorized the cited evidence into 6 different types. Results reflected plan coverage policies for 13 PAH drugs active between August 2017 and August 2022 and issued by 17 large US commercial health plans, representing 70% of covered lives. Coverage restrictions varied mainly by step therapy protocols and prescriber restrictions. Seven plans had step therapy protocols for most drugs, 9 for at least one drug, and 1 had none. Ten plans required specialist (cardiologist or pulmonologist) prescribing for at least one drug, and 7 did not. Coverage restrictions increased over time: the proportion of policies with at least 1 restriction increased from 38% to 73%, and the proportion with step therapy protocols increased from 29% to 46%, with generics as the most common step. The proportion of policies with step therapy protocols increased for every therapy class with generic availability: 18% to 59% for ERAs, 33% to 77% for PDE5is, and 33% to 43% for PPAs. The proportion of policies with prescriber requirements increased from 24% to 48%. Plans updated their policies 58% of the time annually and most often cited the 2019 CHEST clinical guidelines, followed by randomized controlled trials. Plan use of coverage restrictions for PAH therapies increased over time and varied across both drugs and plans. Inconsistency among health plans may complicate patient access and reduce the proportion who can persist on PAH treatments.

Evaluating the Impact of Pulmonary Arterial Hypertension Therapies on Pericardial Effusion and Patient Survival.

To evaluate the impact of Pulmonary Arterial Hypertension (PAH) therapies on the incidence of pericardial effusion and its prognostic implications for patient survival. This retrospective cohort study included 60 patients diagnosed with PAH at a high-volume tertiary care center, treated with intravenous or subcutaneous prostanoids. Data were collected from 2015 to 2019, including echocardiographic assessments, right heart catheterization, World Health Organization functional class evaluations, six-minute walk distance tests, and biomarkers such as brain natriuretic peptide and N-terminal prohormone of brain natriuretic peptide. Follow-up was conducted at least 90 days post-treatment initiation. Pericardial effusion was observed in 31.7% of patients before therapy. Patients with moderate to large effusions had a significantly higher mortality risk (HR = 1.92; 95% CI 1.1-44.78; p =0.0044), while small effusions appeared protective (HR = 0.27; 95% CI 0.15-0.48; p =0.006). Survival rates declined from 89% at one year to 71% at three years post-therapy, with effusion presence correlating with more severe PAH manifestations. Initial pericardial effusion severity is a critical predictor of mortality in PAH patients. Early assessment and stratified management of pericardial effusion are essential for optimizing therapeutic outcomes in PAH management. Future research should explore targeted interventions for managing pericardial effusion to improve patient prognosis.

ARE THERE ANY ADVANTAGES TO USING A POLYPILL OR FREE PILL COMBINATION TO PROTECT PATIENTS WITH ARTERIAL HYPERTENSION AND DYSLIPIDEMIA?

Objective: Arterial hypertension (AH) has been acknowledged as a leading cause of death. Treating AH alone may provide only limited benefits while it is recommendable to manage the total cardiovascular risk. The aim was to assess the treatment of AH and dyslipidemia (DLP) in patients in specialists’ offices. Design and method: This project was conducted from April to June 2023 in 51 specialists’ offices (SPO) (33% cardiology, and 67% internal medicine) in Slovakia. We have enrolled all 18-year-old pts who are willing to complete a short questionnaire and take office BP. Results: We enrolled 514 pts with AH (42% women), mean age 61,5 ± 17,2 years from SPOs. The mean OBP was 134,9 ± 10,9/ 80,3 ± 7,2 mmHg. The average total cholesterol (TC) was 5,7 mmol/l, LDL-C 3,0 mmol/l. TC (6,12 vs 5,15 mmol/l, p<0,01) was higher in male patients, and LDL-C was higher in female patients (3,05 vs 2,91 mmol/l). 76% pts experienced both AH and DLP simultaneously. In comparison to those without HLP, AH patients with HLP were given 0.5 active substances and 0.8 pills more. In total 79% pts with AH and HLP were treated with a free pill combination with a statin, while only 16% were treated with polypill. The use of polypill was more frequent in female pts (18%) vs male pts (14%). Target BP lower than 140/90 mmHg was reached in 68% pts with polypill, and in 53% pts without polypill. Non-HDL- C was lower in pts with polypill (3,6 vs 4,03 mmol/l). The current BP and non-HDL targets were reached more frequently in pts with polypill 56% vs 44% pts. Conclusions: Adherence to medications is important to achieve the full effect of antihypertensive and lipid-lowering drugs. We demonstrated that the use of polypill compared to a free pill combination of statin and AH therapy is more effective. 27% of patients reached BP and LDL targets when were treated by polypill. Using polypill in our pts we aim to reach a higher rate of BP and cholesterol control in Slovakia to meet the objectives of the Charter 70/2023 initiative.

Management of pulmonary vascular disease associated with congenital left-to-right shunts: A single-center experience

ObjectiveThe study objective was to describe the course and outcomes of children under 18 years of age, with left-to-right shunts and pulmonary arterial hypertension undergoing 1 of 2 management approaches: pulmonary arterial hypertension treatment before left-to-right shunt repair (Treat First) and left-to-right shunt repair first with or without subsequent pulmonary arterial hypertension treatment (Repair First). MethodsWe performed a retrospective single-center study, conducted from September 2015 to September 2021, of children with left-to-right shunts and pulmonary arterial hypertension (defined as indexed pulmonary vascular resistance ≥ 4 Wood units [WU]∗m2) but without Eisenmenger physiology. Patient characteristics, longitudinal hemodynamics data, pulmonary arterial hypertension management, left-to-right shunt repair, and outcomes were reviewed. ResultsOf 768 patients evaluated for left-to-right shunt closure, 51 (6.8%) had left-to-right shunts associated with pulmonary arterial hypertension (median age 1.1 [0.37-5] years, median indexed pulmonary vascular resistance 6 [5.2-8.7] WU∗m2). In the "Treat First" group (n = 33, 65%), 27 patients (82%) underwent left-to-right shunt closure and 6 patients (18%) did not respond to pulmonary arterial hypertension therapy and did not undergo left-to-right shunt closure. In the "Repair First" group (n = 18, 35%), 12 patients (67%) received pulmonary arterial hypertension therapy and 6 patients (33%) did not. Mortality rates were 6% in the "Treat First" group and 11% in "Repair First" group with follow-ups of 3.4 and 2.5 years, respectively. After left-to-right shunt closure, there was no significant change in indexed pulmonary vascular resistance over a median follow-up of 2 years after surgery (P = .77). ConclusionsIn children with left-to-right shunts and associated pulmonary arterial hypertension, treatment with pulmonary arterial hypertension–targeted therapy before defect repair does not appear to endanger the subjects and may have some benefit. The response to pulmonary arterial hypertension–targeted therapy before shunt closure persists 2 to 3 years postclosure, providing valuable insights into the long-term management of these patients.

Strategies for choosing combination therapy for hypertension in metabolic syndrome - focus on inflammation

The article substantiates the need for adequate fixed combination therapy for metabolic syndrome and arterial hypertension (AH). The issues of inflammation in the initiation and stabilization of arterial hypertension in patients with metabolic syndrome (MS) are considered. Taking into account the results of international and Russian studies, a differentiated approach is proposed to select a fixed combination of antihypertensive drugs for the treatment of hypertension and prevention of cardiovascular complications in patients with MS.

Use of pulmonary arterial hypertension therapies in patient swith sarcoidosis-associated pulmonary hypertension.

Use of pulmonary arterial hypertension therapies in patient swith sarcoidosis-associated pulmonary hypertension.

Survival and response to pulmonary vasodilator therapies in patients with chronic obstructive pulmonary disease and pulmonary vascular phenotype

BackgroundThe aim of the study was to describe and investigate the effect of pulmonary arterial hypertension (PAH) therapies in a cohort of patients with severe precapillary pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD; PH-COPD), and to assess factors predictive of treatment response and mortality. Material and methodsWe retrospectively included patients with severe incident PH-COPD who received PAH therapy and underwent RHC at diagnosis and on treatment. ResultsFrom 2015 to 2022, 35 severe PH-COPD patients, with clinical features of pulmonary vascular phenotype, were included. Seventeen (48.5%) patients were treated with combined PAH therapy. PAH therapy led to a significant improvement in hemodynamics (PVR -3.5 Wood Units (−39.3%); p < 0.0001), and in the simplified four-strata risk-assessment score, which improved by at least one category in 21 (60%) patients. This effect was more pronounced in patients on dual therapy. Kaplan-Meier estimated survival rates at 1, 3 and 5 years were 94%, 65% and 42% respectively. Univariate analysis showed a significant reduction in survival in patients with a higher simplified risk score at follow-up (Hazard ratio (HR) 2.88 [1.16–7.15]; p = 0.02). Hypoxemia <50 mmHg was correlated to mortality in multivariate analysis (HR 4.33 [1.08–17.42]; p = 0.04). ConclusionsOur study confirms the poor prognosis of patients with COPD and a pulmonary vascular phenotype and the potential interest of combined PAH therapy in this population, with good tolerability and greater clinical and hemodynamic improvement than monotherapy. Using the simplified risk score during follow-up could be of interest in this population.

The influence of some general diseases for changes on the ocular surface after trabeculectomy

BACKGROUND: By now, possible effects of diabetes mellitus and arterial hypertension on the ocular surface changes after trabeculectomy have not been evaluated. AIM: Analysis of the effects of arterial hypertension therapy and diabetes mellitus on the ocular surface changes after trabeculectomy. MATERIALS AND METHODS: The study group consisted of 443 patients, including those with arterial hypertension (179 patients), non insulin dependent compensated type 2 diabetes mellitus (25 patients) and their combination (53 persons), operated in 2016–2020 in the City Multifield Hospital No. 2, Saint-Petersburg, for primary open-angle noncompensated glaucoma and then observed for 6 to 24 months. The dynamics of ocular surface disease index (OSDI), tear film break-up time (TBUT), and amount of total tear production has been studied. RESULTS: The probability of the trabeculectomy success did not depend on the concomitant comorbidity. In contrast to intraocular pressure, the criteria for subjective and objective assessment of the ocular surface state were not subject to such obvious changes. In diabetic patients, the studied criteria have not changed compared to the baseline. CONCLUSIONS: The mentioned systemic diseases do not influence the state of the ocular surface in patients with glaucoma, and are not an independent risk factor for the failure of the IOP-lowering surgical procedure. The presence of diabetes mellitus prevents the accompanying a successful trabeculectomy regression of symptoms and clinical and functional signs of dry eye disease.

Drug therapy for arterial hypertension and atrial fibrillation in frail patients : Are there any new insights and recommendations?

The frail and elderly are considered to be at particular risk of suffering an adverse drug reaction. Empirical studies confirm the increased rate of adverse drug reactions. Whether frailty perse impairs drug metabolism or the underlying organ ageing processes and multimorbidity cannot be answered with certainty based on current data. Cardiovascular diseases exhibit aconsiderable interdependence with frailty. For example, there is adisproportionate syndromal interdependence between heart failure and frailty, and the typical ageing processes of the sinus node can be interpreted as heartbeat frailty. Multimorbidity in the elderly often includes acluster of chronic cardiovascular diseases, often leading to the use of several cardiovascular medications as required. More recent definitions of polypharmacy assess the appropriateness of drugs rather than their number. The Fit-fOR-The-Aged (FORTA) list, the PRISCUS 2.0 list and the "Cochrane Library Special Collection on deprescribing", for example, offer apractice-oriented assessment aid. In the treatment of arterial hypertension, the target values for older people have also been set ever lower in recent years. In the case of frail elderly people, on the other hand, the guidelines do not specify astrict blood pressure target corridor; tolerability is the crucial factor here. When initiating antihypertensive therapy in frail individuals, one can consider monotherapy-in adeparture from the standard case of dual combination therapy. The OPTIMISE study showed that discontinuation of one blood pressure medication did not lead to better tolerability of the drug therapy. Current studies come to differing conclusions regarding the risk-benefit assessment of new oral anticoagulants compared to vitaminK antagonists in the anticoagulation of frail elderly people with atrial fibrillation. Shared decision-making, which could improve adherence particularly in older people, is recommended.

Cluster analysis identifies novel real-world lung disease-pulmonary hypertension subphenotypes: implications for treatment response.

Clinical trials repurposing pulmonary arterial hypertension (PAH) therapies to patients with lung disease- or hypoxia-pulmonary hypertension (PH) (classified as World Health Organization Group 3 PH) have failed to show a consistent benefit. However, Group 3 PH clinical heterogeneity suggests robust phenotyping may inform detection of treatment-responsive subgroups. We hypothesised that cluster analysis would identify subphenotypes with differential responses to oral PAH therapy. Two k-means analyses were performed on a national cohort of US veterans with Group 3 PH; an inclusive model (I) of all treated patients (n=196) and a haemodynamic model (H) limited to patients with right heart catheterisations (n=112). The primary outcome was organ failure or all-cause mortality by cluster. An exploratory analysis evaluated within-cluster treatment effects. Three distinct clusters of Group 3 PH patients were identified. In the inclusive model (C1I n=43, 21.9%; C2I n=102, 52.0%; C3I n=51, 26.0%), lung disease and spirometry drove cluster assignment. By contrast, in the haemodynamic model (C1H n=44, 39.3%; C2H n=43, 38.4%; C3H n=25, 22.3%), right heart catheterisation data surpassed the importance of lung disease and spirometry. In the haemodynamic model, compared to C3H, C1H experienced the greatest hazard for respiratory failure or death (HR 6.1, 95% CI 3.2-11.8). In an exploratory analysis, cluster determined treatment response (p=0.006). Conclusions regarding within-cluster treatment responses were limited by significant differences between select variables in the treated and untreated groups. Cluster analysis identifies novel real-world subphenotypes of Group 3 PH patients with distinct clinical trajectories. Future studies may consider this methodological approach to identify subgroups of heterogeneous patients that may be responsive to existing pulmonary vasodilatory therapies.

A brief overview of modern approaches to the therapy of resistant arterial hypertension

Resistant hypertension is associated with increased mortality and morbidity. The optimal drug therapy for resistant hypertension has not been fully clarified, there are few studies on this issue in the literature. We compared the efficacy of nebivolol 5 mg, a third-generation beta-blocker, with spironolactone 25 mg in patients with resistant hypertension.&#x0D; 81 patients with resistant hypertension were included in the study. Resistant hypertension was defined as the presence of official blood pressure ≥ 140/90 mm Hg. when patients received 3 or more antihypertensive drugs, including diuretics. Blood pressure was recorded in office and outpatient settings at baseline and after 8 weeks of treatment.&#x0D; Office systolic blood pressure and diastolic blood pressure at 24-hour ambulatory blood pressure monitoring were significantly lower compared to baseline values in the nebivolol and spironolactone groups. The decrease in 24-hour mean systolic and diastolic blood pressure in the nebivolol group was 14.9±19.8 mm Hg. Art. and 9.3±12.7 mm Hg. Art. compared to 19.5±16.4 mm Hg. Art. and 13.7±10.8 mm Hg. Art. in the spironolactone group, respectively. The reduction in 24-hour mean systolic and diastolic blood pressure was not significantly different between the nebivolol and spironolactone groups (P = 0.338 and P = 0.153).&#x0D; Therefore, nebivolol is an effective treatment option for resistant hypertension, and the antihypertensive effect of this drug is similar to low doses of spironolactone.

Analysis of the list of medicines for arterial hypertension therapy during pregnancy

Preserving the pregnant women health is one of the most important task in the health care system. In 2020, more than 21,000 cases of hypertensive disorders were diagnosed during pregnancy in Ukraine. Arterial hypertension during pregnancy is the main risk factor for negative consequences for the child and mother. During pregnancy, antihypertensive therapy reduces the risk of morbidity or premature birth, as well as adverse effects to the fetus/newborn.&#x0D; The purpose of the study was to analyze the list of registered antihypertensive medicines under the INN, which are presented on the domestic pharmaceutical market, and to analyze their socio-economic availability.&#x0D; Research materials and methods. Analysis of antihypertensive medicines in accordance with national recommendations for the arterial hypertension treatment during pregnancy in Ukraine; analysis of the State Register of Medicinal Products of Ukraine, the National List of Essential Medicines, the State Formulary of Medicines (15 issue). Data from the information resource «Tabletki.ua» were used to determine the pharmaceuticals prices. Methods – information search, analysis, generalization, marketing research, «minimization of cost» method, calculation of socio-economic affordability ratios – the liquidity ratio Cliq, the ratio of adequacy solvency Ca.s.&#x0D; The results of the analysis of antihypertensive medicines that are registered and have indications during pregnancy showed that the following medicines with INNs are available on the pharmaceutical market: methyldopa, nifedipine, metoprolol tartrate, esmolol, nicardipine, uradipyl, but the following INNs labetalol, hydralazine, acebutolol, mepindolol, oxprenolol are missing. It was established that the list of antihypertensive medicines used during pregnancy is represented by 33 trade names of various medicinal forms from 10 countries of the world, the specific weight of which is 69% of medicines of foreign production. There is an insufficient amount of methyldopa medicines on the domestic pharmaceutical market, as there is only one name of a foreign manufacturer.&#x0D; It was determined by the «cost minimization» method that the costs for one month of treatment when using nifedipine of a domestic manufacturer compared to a drug of a foreign manufacturer are lower by 90%. For metoprolol of the domestic manufacturer, the costs are 73% lower than for the imported drug.&#x0D; The socio-economic availability of medicines was determined using the price liquidity ratio and the solvency adequacy ratio, which indicated relatively adequate price competition and the high availability of most antihypertensive medicines for the population of Ukraine.