Therapy For Arterial Hypertension Research Articles

Arterial hypertension and anticancer drug therapy: pathophysiological relationships and clinical significance

Arterial hypertension (AH) is one of the most common cardiovascular complications of anticancer drug therapy. In this review article, we consider the main groups of anticancer drugs that may cause the development of iatrogenic AH, the pathophysiological mechanisms of increased blood pressure, as well as the clinical significance of AH developed during treatment with cytostatics and targeted drugs in the practice of an oncologist and a cardiologist. It was found that AH is frequently associated with the use of angiogenesis inhibitors, as well as alkylating cytostatics, antimetabolites, taxanes, and proteasome inhibitors. In addition, erythropoietins, glucocorticosteroids, and non-steroidal anti-inflammatory drugs used as part of supportive therapy may contribute to an increase in blood pressure. Management of hypertension in cancer patients is an important part of antitumor treatment therapy whose implementation contributes to improving their quality of life. Research into various clinical and pathophysiological aspects of cardiovascular disorders in cancer patients is becoming increasingly relevant, which is indicated by the rapid development of cardio-oncology, a new interdisciplinary field of knowledge aimed at developing practical recommendations for the prevention, diagnosis, and treatment of cardiovascular toxicity caused by anticancer therapy.

EFFECTIVENESS OF СOMBINED REHABILITATION THERAPY IN KIDS WITH METABOLIC SYNDROME

Abstract The work carried out a multivariate study of the mechanisms of metabolic disorders, closely related to an increase in blood pressure in children with arterial hypertension from 10 to 17 years. For this purpose, 60 children with arterial hypertension and metabolic disorders were examined. 20 children made up the control group. Before and after spa treatment, all children underwent a set of clinical and laboratory examinations, which included daily monitoring of blood pressure, biochemical studies of lipid and carbohydrate profiles, insulin, insulin resistance indices HOMO and CARO, leptin, adiponectin. Besides the individual hypocaloric diet, the rehabilitation included proper physical activity, school of arterial hypertension, not allowing for a child to sit at the computer or watch TV for a long time (or at all), treatment of foci of chronic infection (including pelotherapy and inhalations), sedative aero-phytotherapy, aero-ionotherapy, exercise therapy in either arterial hypertension or obesity group, classical hand massage of the neck and shoulders, electrosleep therapy. Depending on the treatment received the children with arterial hypertension (n=60) were divided into three groups (using the method of simple randomisation). The use of balneotherapy and electrosleep therapy in complex spa treatment contributes to the normalization of initially disturbed biochemical carbohydrate and lipid metabolic markers, a decrease in high levels of leptin and insulin, and an increase in initially reduced adiponectin. This allows us to conclude that the combined sanatorium-resort rehabilitation of patients is highly effective, which is expressed in a decrease in blood pressure, body weight, indicators of fat and carbohydrate metabolism. Intensive spa treatment has a beneficial effect on changing the criteria for the development of MS in children with obesity and hypertension. Of course, to achieve the optimal effect in the correction of disorders of carbohydrate and lipid metabolism, a long period of therapeutic measures and observation of patients is required, at least 3-6 months.

Combination therapy of newly diagnosed intermediate-risk pulmonary arterial hypertension: A review

Advancements in the specific therapy of pulmonary arterial hypertension (PAH) and new combination therapy strategies and escalation treatment over the past decade have significantly improved disease control, slowed its progression, and improved quality of life and patient survival. This review provides a detailed discussion of current strategies for PAH-specific therapy available in the Russian Federation for patients with classical and non-classical PAH who fail to achieve treatment goals and remain at intermediate risk of disease progression/mortality.

Drug therapy of arterial hypertension: assessment of the senior students’ basic knowledge. Final results of the PHYSTARH project

Introduction. Arterial hypertension (AH) is the main correctable cause of the development of cardiovascular diseases, leading to dysfunction of many organs, including the heart, blood vessels and kidneys. Lack of adequate control of systolic and/or diastolic blood pressure can lead to life-threatening conditions and death.The aim of study is to analyze the senior medical students’ knowledge from different regions of Russia in the basic issues of hypertension therapy.Materials and methods. The article presents the results of the first stage of the PHYSTARH multicenter study (the full name of the project is Physicians’ and undergraduates’ knowledge in arterial hypertension treatment): an anonymous survey among 285 senior medical students from 4 cities of Russia. In this article, the authors analyzed the questions of the second part of the questionnaire.Results. The average level of correct answers on the questionnaire was 57.7%. The minimum level of correct answers was obtained in questions about the effectiveness of combined therapy, as well as the choice of absolute contraindications to the use of antihypertensive drugs. The maximum level of correct answers was registered in the question about determining the drug to its pharmacological group.Conclusion. The obtained results testify to the insufficiently level of students’ knowledge in the basic issues of arterial hypertension therapy.

Percutaneous transcatheter treatment of hypertension and heart failure: results of the SICI-GISE national survey promoted by the GISE Young Committee

During the last decade, thanks to contemporary evidence and technological improvements, the role of interventional cardiology in the field of cardiac conditions that are mainly treated conservatively has grown a lot. In such scenario, drug-resistant arterial hypertension and heart failure (HF) have a significant role, considering the huge number of involved patients and their impact on mortality and quality of life. This survey was jointly performed by the GISE Young Committee with the support of the SICI-GISE Society and the ICOT group with the aim of evaluating the view of the cardiology community on interventional therapies for arterial hypertension and HF. A web-based questionnaire based on 22 questions was distributed online to SICI-GISE members. The survey was distributed to 1550 physicians with 156 (10%) responses, 58% of whom was under 35 years of age. Renal denervation was available in 49% of Centers, its principal indication was the evidence of severe adverse reactions to anti-hypertensive drugs (80%). Most participants agreed that, compared to past years, there is more understanding of anatomical characteristics and improvement of devices, thus increasing procedural safety; however, main limitations were: appropriate patients' selection criteria (45%), lack of robust evidence (41%) and regulatory (36%) and economical (33%) factors. In the field of HF, this survey enlightened a wide availability of conventional therapies (i.e. mechanical circulatory support, defibrillators, resynchronization) in Italy; on the other side, there is limited availability of innovative devices (i.e. atrial decompression systems, transcatheter left ventricular reshaping). Many participants expressed enthusiastic attitude in this new field, with a look for the need of further evidence in terms of safety and efficacy. Finally, in the treatment of both acute and chronic HF, many participants expressed a problem of limited patient access to advanced therapies, mainly associated with suboptimal networking among institutions. Device-based therapies for arterial hypertension and HF represent a promising option for selected patients; this survey highlights the importance of achieving good quality evidence in both fields, with the goal of proper identification of defined criteria for patients' selection and improvement of procedural and long-term safety and efficacy.

Comparative study of the specific activity of soft application drugs with vinpocetine

In modern neurology, the main component of successful treatment of cerebrovascular pathology is pharmacotherapy. At the same time, the arsenal of effective medicines of evidence-based medicine in this area is quite limited. Vinpocetine (Cavinton) is one of the drugs that effectively selectively corrects cerebral perfusion. The use of alternative ways of absorption of vinpocetine (rectal and nasal) in certain soft application dosage forms will allow to significantly increase the bioavailability of the medicinal substance, reduce the level of adverse reactions from its use and expand the pharmacotherapeutic arsenal of domestic effective neuroprotective drugs. Taking into account the above, the employees of the Department of Medicines Technology of Zaporizhzhia State Medical University, on the basis of complex physical-chemical, pharmacotechnological, rheological and biopharmaceutical research, proposed rational formulations and technologies of two new soft application dosage forms of vinpocetine – rectal suppositories on a lipophilic basis and nasal cream on an emulsion basis for the therapy of arterial hypertension of II–III stages with cerebrovascular complications, reduction of the manifestation of neurological and/or mental symptoms in various forms of cerebral blood circulation insufficiency, consequences of a stroke, transient ischemic attack, etc. The aim of the work is to study the specific activity of the proposed innovative application dosage forms of vinpocetine. Materials and methods. Nasal ointment containing 0.5 % vinpocetine on an emulsion basis and rectal suppositories with vinpocetine 0.01 g on a lipophilic carrier were used as the object of preclinical studies, which ensure optimal release of the active pharmaceutical ingredient. The study of the specific activity of the developed medicinal forms of vinpocetine was carried out on a model of acute cerebrovascular accident of the type of ischemic stroke. Vinpocetin tablets (Astrapharm, Ukraine), which are used in neurological practice quite effectively and over a long period of time, were used as a comparison drug. Results. The comparative results showed that the appointment of all studied drugs led to an increase in motor activity. In addition, the administration of medicinal forms of vinpocetine reduced the development of cognitive and cognitive disorders after acute disorders of cerebral blood circulation. It was found that the highest result was shown by the group of animals that received a course of vinpocetine intranasally. In the groups of animals that received vinpocetine for 4 days, markers of oxidative stress – aldehyde phenylhydrazones and ketone phenylhydrazones – were significantly reduced. The highest activity was demonstrated by the pharmaceutical form of vinpocetin, which was used intranasally for 4 days. The introduction of dosage forms of vinpocetine exerted an energizing effect, which was expressed in an increase in the level of macroergic phosphates. Evidently, vinpocetine has a direct positive effect on the three-carbon sections of the Krebs cycle and increases the production of adenosine triphosphate (ATP). At the same time, the vinpocetine nasal cream applied intranasally for 4 days demonstrated the greatest energizing activity. Conclusions. Preclinical studies of the developed application soft medicines with vinpocetine on the model of acute cerebrovascular accident type ischemic stroke experimentally confirmed the expressed neuroprotective activity of rectal suppositories and nasal cream with vinpocetine and it was found that the effectiveness of therapy with these application medicinal forms is demonstrably higher than that in comparison with oral tablet means.

Efficacy and dose-response relationship of oral treprostinil in PAH patients on monotherapy or dual background therapy

Abstract Background FREEDOM-C and FREEDOM-C2 were randomized, placebo-controlled, double-blinded international, multicenter studies investigating the use of oral treprostinil (TRE) in subjects on mono or dual background pulmonary arterial hypertension (PAH) therapies. Both had a primary endpoint of change in 6-minute walk distance (6MWD) at Week 16 vs baseline. Previous post-hoc analyses combining mono and dual therapy subjects (PDE-5i and/or ERA) from these studies revealed a TRE dose-dependent increase in 6MWD. (1. White & Rao, 2016) Purpose This post-hoc analysis was performed to determine if subjects from FREEDOM-C and FREEDOM-C2 derive improvements in 6MWD with increasing doses of TRE when stratified by mono or dual background therapy and to determine if PAH background therapies (mono or dual) impacted 6MWD. Methods All active subjects (n=331) from FREEDOM-C and FREEDOM-C2 were grouped into TRE dose tertiles (low-dose: ≤2 mg BID, mid-dose: >2 mg to ≤3.5 mg BID, and high-dose: >3.5 mg BID). Placebo subjects (n=329) were in a separate 0 mg dose group. No data imputation was implemented. Comparisons of 6MWD change at Weeks 4, 8, 12, and 16 between mono and dual therapy subgroups at any dose group were performed using a two-sample t-test or nonparametric Wilcoxon rank-sum test. The nonparametric Kruskal-Wallis test was conducted with subsequent pairwise comparisons of 6MWD change at Week 16 between the four dose groups through Dunn's approach. Additionally, the Jonckheere-Terpstra test was used to assess the linear trend for 6MWD improvement with higher doses of TRE. Results Baseline characteristics of the combined intention to treat (ITT) population and summary of 6MWD for subjects with both baseline and Week 16 data are in Table 1. 6MWD change improved steadily to Week 16 in subjects at higher TRE doses, regardless of the number of PAH background therapies (Figure 1). No statistical differences were found between mono and dual therapy at any time point or for any dose group. At Week 16, there was a significant difference in 6MWD change between the placebo group and high dose group within both mono and dual background therapy subjects. The difference between the low- and high-dose groups was significant for subjects on dual background therapy. There was a significant positive linear trend for TRE doses in 6MWD improvement at Week 16 for both monotherapy subjects (one-sided p-value = 0.0002) and dual therapy subjects (one-sided p-value = 0.0242). Conclusions 6MWD improved in PAH patients regardless of their background therapy (monotherapy or dual background) and derive greater 6MWD improvements with higher doses of TRE. The observed dose-dependent 6MWD increase supports the use of TRE in sequential combination with background therapies (mono or dual). Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): United Therapeutics Corporation

BURDEN OF ILLNESS IN PATIENTS WITH PULMONARY HYPERTENSION DUE TO COPD IN US ADMINISTRATIVE CLAIMS DATA

BURDEN OF ILLNESS IN PATIENTS WITH PULMONARY HYPERTENSION DUE TO COPD IN US ADMINISTRATIVE CLAIMS DATA

Improved Survival for Patients with Systemic Sclerosis-associated Pulmonary Arterial Hypertension: The Johns Hopkins Registry.

Rationale: To date, it remains unclear whether recent changes in the management of patients with systemic sclerosis-associated pulmonary hypertension (SSc-PH) have improved survival. Objectives: To describe a cohort of patients with SSc-PH and compare their characteristics and survival between the last two decades. Methods: Patients with SSc-PH prospectively enrolled in the Johns Hopkins Pulmonary Hypertension Center Registry were grouped into two cohorts based on the date of diagnostic right heart catheterization: cohort A included patients whose disease was diagnosed between 1999 and 2010, and cohort B included those whose disease was diagnosed between 2010 and 2021. Patients' characteristics were compared between the two cohorts. Measurements and Main Results: Of 504 patients with SSc-PH distributed almost equally between the two cohorts, 308 (61%) had World Symposium on Pulmonary Hypertension group 1, 43 (9%) had group 2, and 151 (30%) had group 3 disease. Patients with group 1 disease in cohort B had significantly better clinical and hemodynamic characteristics at diagnosis, were more likely to receive upfront combination pulmonary arterial hypertension therapy, and had a nearly 4-year increase in median transplant-free survival in univariable analysis than those in cohort A (P < 0.01). Improved transplant-free survival was still observed after adjusting for patients' baseline characteristics. In contrast, for group 2 or 3 patients with SSc-PH, there were no differences in baseline clinical, hemodynamic, or survival characteristics between the two cohorts. Conclusions: This is the largest single-center study that compares clinical characteristics of patients with SSc-PH between the last two decades. Transplant-free survival has improved significantly for those with group 1 disease over the last decade, possibly secondary to earlier detection and better therapeutic management. Conversely, those with group 2 or 3 disease continue to have dismal prognosis.

Knowledge on arterial hypertension therapy in outpatients in Novi Sad

Knowledge on arterial hypertension therapy in outpatients in Novi Sad

Antihypertensive therapy of late arterial hypertension in children following successful coarctation correction.

Late arterial hypertension (AH) is the most significant complication of coarctation of the aorta (CoA). Only a few clinical studies described antihypertensive treatment of late AH following successful CoA repair. The primary objective of this multicentre cross-sectional study was to describe real-life antihypertensive therapy for late AH in children after hemodynamically successful CoA repair. The secondary objective was to describe antihypertensive therapy used within different haemodynamic phenotypes of AH. Blood pressure status, echocardiographic parameters and central blood pressure measurements were evaluated in 110 children aged 6-18 years following successful CoA repair with right arm blood pressure not exceeding leg blood pressure by at least 20 mmHg. AH was found in 62 (56%) patients including 47 who were already treated and 15 with new diagnosed AH of whom seven presented with masked hypertension. Among treated patients, 10 presented with masked hypertension. The dominant phenotype of AH among patients with uncontrolled AH was isolated systolic hypertension (32 patients out of 37; 87.5%). AH was controlled in 53% of treated patients. Fifty-three percent of hypertensive patients had elevated central SBP and 39% had left ventricular hypertrophy with various left ventricle geometry patterns, 23% of them had both. β-adrenergic receptor blockers were the most used antihypertensive drugs followed by angiotensin-converting enzyme inhibitors with doses within the lower recommended range. High prevalence of uncontrolled AH despite successful CoA repair and use of relatively low doses of antihypertensive drugs indicates the need of close blood pressure monitoring and more intensive and combined antihypertensive therapy.

Фармакотерапевтичні особливості ведення пацієнтів із вторинними артеріальними гіпертензіями ендокринного генезу

Secondary arterial hypertension is the arterial hypertension, the etiology of which can be established. Secondary arterial hypertension becomes the cause of elevated blood pressure in 5–10% of patients with hypertension. More than 50 diseases and clinical conditions contributing to the development of secondary arterial hypertension have been identified. In most cases, such arterial hypertension is characterized by high blood pressure, an unfavorable prognosis of the disease, and a high frequency of cardiovascular complications. However, in some forms of it, timely diagnosis and adequate treatment allow to achieve normalization of blood pressure and prevent the development of complications. In cases of the secondary arterial hypertension, in addition to antihypertensive therapy, drug treatment or surgical treatment of the underlying disease that caused hypertension is required. Knowledge of modern diagnostics and principles of treatment of these conditions has to improve the quality of care for patients suffering from hypertension. The purpose of the study was to consider the main clinical, pathogenic, diagnostic and pharmacotherapeutic aspects of the secondary arterial hypertension of endocrine genesis. Secondary endocrine arterial hypertensions develop in diabetes mellitus, hyperaldosteronism primary (Kon's syndrome) and pseudoprimary (idiopathic hyperplasia of the adrenal cortex), Itsenko-Cushing syndrome, pheochromocytoma, pheochromoblastoma, paraganglioma, acromegaly, hypothyroidism, hyperthyroidism, hyperparathyroidism, etc. Each of these diseases has a special etiopathogenesis of arterial hypertension, which makes it necessary to carry out special screening and diagnostic tests in order to prescribe reasonable therapy. In the management of patients with secondary endocrine arterial hypertension, there cannot be universal approaches to the appointment of antihypertensive drugs, instead, an individualized approach contributes to effective control of the disease and prevention of possible complications. Conclusion. So, taking into account the high and progressive incidence of arterial hypertension worldwide, the high frequency of life-threatening complications, a large number of risk factors, constant updating of knowledge on the clinical, pathogenic, diagnostic and pharmacotherapeutic aspects of the management of such patients becomes extremely relevant. A significantly large part of secondary arterial hypertension in the structure of this pathology requires special attention of practicing doctors regarding differential diagnosis, especially in the cohort of young patients. Information about features of the pathogenic therapy of the secondary arterial hypertension of endocrine origin is necessary for a wide range of doctors of various specialties for the maximum effective management of such patients

2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.

2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.

The Paradox of Pulmonary Vascular Resistance: Restoration of Pulmonary Capillary Recruitment as a Sine Qua Non for True Therapeutic Success in Pulmonary Arterial Hypertension.

Exercise-induced increases in pulmonary blood flow normally increase pulmonary arterial pressure only minimally, largely due to a reserve of pulmonary capillaries that are available for recruitment to carry the flow. In pulmonary arterial hypertension, due to precapillary arteriolar obstruction, such recruitment is greatly reduced. In exercising pulmonary arterial hypertension patients, pulmonary arterial pressure remains high and may even increase further. Current pulmonary arterial hypertension therapies, acting principally as vasodilators, decrease calculated pulmonary vascular resistance by increasing pulmonary blood flow but have a minimal effect in lowering pulmonary arterial pressure and do not restore significant capillary recruitment. Novel pulmonary arterial hypertension therapies that have mainly antiproliferative properties are being developed to try and diminish proliferative cellular obstruction in precapillary arterioles. If effective, those agents should restore capillary recruitment and, during exercise testing, pulmonary arterial pressure should remain low despite increasing pulmonary blood flow. The effectiveness of every novel therapy for pulmonary arterial hypertension should be evaluated not only at rest, but with measurement of exercise pulmonary hemodynamics during clinical trials.

Clinical efficacy of combination therapy of arterial hypertension in patients with chronic glomerulonephritis with different blood pressure salt sensitivity

Arterial hypertension is the main factor in the progression of CKD of any etiology; therefore, effective antihypertensive therapy is a crucial task of healthcare practice. In this work, the authors aim to study the comparative effectiveness of various types of combined antihypertensive therapy in patients with different blood pressure salt sensitivity.

Population aspects of arterial hypertension therapy. Focus on fixed combinations

High blood pressure (BP) remains the leading risk factor for coronary heart disease, stroke, other cardiovascular diseases, chronic kidney disease, and dementia. Objective. To estimate the frequency of prescribing antihypertensive drugs (AHD) with the allocation of the proportion of fixed combinations (FC) among people aged 25–64 years examined in 16 regions of the Russian Federation as part of the ESSE-RF and ESSE-RF2 studies.Design and methods. The analysis included the results of a survey of representative samples of the population of the Russian Federation in the ESSE-RF studies (2012–2014, men: N = 8376 and women N = 13546 people) and ESSE-RF2 (2017, men: N = 3000 and women N = 3714 people). Each participant signed an informed consent. Arterial hypertension (AH) was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg and/or if the examined reported taking AHD. Under the lack of control of AH, we understood the proportion of patients (%) with BP levels ≥ 140/90 mm Hg of the total number of patients with AH. Information about the AHD taken was recorded from the words of the patient (trade name of the drug) followed by coding according to the International Nonproprietary Names of Drugs.Results. In the Russian population, there was a decrease in the proportion of uncontrolled BP from 78,5 % (95 % confidence interval (CI) 77,7–79,3) in ESSE-RF to 73,0% (95 % CI 71,3–74,6) in ESSE-RF2. FC intake was detected in 15,6 % (95 % CI 13,8–18,0) of patients treated in the ESSE-RF study, while the proportion of such patients in the ESSE-RF2 decreased to 10,9% (95% CI 9,2–12,8), p &lt; 0,001. The most common FC was the combination of an angiotensin-converting enzyme inhibitors (ACEI) and a diuretic (ESSE-RF: 49,1 % and ESSE-RF2: 45,9 %). In second place in ESSE-RF is a diuretic + angiotensin receptor blockers (25,8 %), in ESSE-RF2 — calcium channel blockers (CCB) + ACEI (22,4%). A more modern combination, namely: the combination of ACEI and CCB, was noted only in 8,7% in ESSE-RF, while in ESSE-RF2 the proportion of this FC increased by 2,5 times.Conclusions. In the population of the Russian Federation, only 10 %-15 % of patients with AH receive FC AHD. An increase in FC intake may contribute to an increase in adherence to therapy, which is extremely important for the Russian population with poor BP control.

Phenotyping of idiopathic pulmonary arterial hypertension: a registry analysis

SummaryBackgroundAmong patients meeting diagnostic criteria for idiopathic pulmonary arterial hypertension (IPAH), there is an emerging lung phenotype characterised by a low diffusion capacity for carbon monoxide (DLCO) and a smoking history. The present study aimed at a detailed characterisation of these patients.MethodsWe analysed data from two European pulmonary hypertension registries, COMPERA (launched in 2007) and ASPIRE (from 2001 onwards), to identify patients diagnosed with IPAH and a lung phenotype defined by a DLCO of less than 45% predicted and a smoking history. We compared patient characteristics, response to therapy, and survival of these patients to patients with classical IPAH (defined by the absence of cardiopulmonary comorbidities and a DLCO of 45% or more predicted) and patients with pulmonary hypertension due to lung disease (group 3 pulmonary hypertension).FindingsThe analysis included 128 (COMPERA) and 185 (ASPIRE) patients with classical IPAH, 268 (COMPERA) and 139 (ASPIRE) patients with IPAH and a lung phenotype, and 910 (COMPERA) and 375 (ASPIRE) patients with pulmonary hypertension due to lung disease. Most patients with IPAH and a lung phenotype had normal or near normal spirometry, a severe reduction in DLCO, with the majority having no or a mild degree of parenchymal lung involvement on chest computed tomography. Patients with IPAH and a lung phenotype (median age, 72 years [IQR 65–78] in COMPERA and 71 years [65–76] in ASPIRE) and patients with group 3 pulmonary hypertension (median age 71 years [65–77] in COMPERA and 69 years [63–74] in ASPIRE) were older than those with classical IPAH (median age, 45 years [32–60] in COMPERA and 52 years [38–64] in ASPIRE; p<0·0001 for IPAH with a lung phenotype vs classical IPAH in both registries). While 99 (77%) patients in COMPERA and 133 (72%) patients in ASPIRE with classical IPAH were female, there was a lower proportion of female patients in the IPAH and a lung phenotype cohort (95 [35%] COMPERA; 75 [54%] ASPIRE), which was similar to group 3 pulmonary hypertension (336 [37%] COMPERA; 148 [39%] ASPIRE]). Response to pulmonary arterial hypertension therapies at first follow-up was available from COMPERA. Improvements in WHO functional class were observed in 54% of patients with classical IPAH, 26% of patients with IPAH with a lung phenotype, and 22% of patients with group 3 pulmonary hypertension (p<0·0001 for classical IPAH vs IPAH and a lung phenotype, and p=0·194 for IPAH and a lung phenotype vs group 3 pulmonary hypertension); median improvements in 6 min walking distance were 63 m, 25 m, and 23 m for these cohorts respectively (p=0·0015 for classical IPAH vs IPAH and a lung phenotype, and p=0·64 for IPAH and a lung phenotype vs group 3 pulmonary hypertension), and median reductions in N-terminal-pro-brain-natriuretic-peptide were 58%, 27%, and 16% respectively (p=0·0043 for classical IPAH vs IPAH and a lung phenotype, and p=0·14 for IPAH and a lung phenotype vs group 3 pulmonary hypertension). In both registries, survival of patients with IPAH and a lung phenotype (1 year, 89% in COMPERA and 79% in ASPIRE; 5 years, 31% in COMPERA and 21% in ASPIRE) and group 3 pulmonary hypertension (1 year, 78% in COMPERA and 64% in ASPIRE; 5 years, 26% in COMPERA and 18% in ASPIRE) was worse than survival of patients with classical IPAH (1 year, 95% in COMPERA and 98% in ASPIRE; 5 years, 84% in COMPERA and 80% in ASPIRE; p<0·0001 for IPAH with a lung phenotype vs classical IPAH in both registries).InterpretationA cohort of patients meeting diagnostic criteria for IPAH with a distinct, presumably smoking-related form of pulmonary hypertension accompanied by a low DLCO, resemble patients with pulmonary hypertension due to lung disease rather than classical IPAH. These observations have pathogenetic, diagnostic, and therapeutic implications, which require further exploration.FundingCOMPERA is funded by unrestricted grants from Acceleron, Bayer, GlaxoSmithKline, Janssen, and OMT. The ASPIRE Registry is supported by Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.

Notopterol Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat.

IntroductionCurrent targeted pulmonary arterial hypertension (PAH) therapies have improved lung hemodynamics, cardiac function, and quality of life; however, none of these have reversed the ongoing remodeling of blood vessels. Considering notopterol, a linear furocoumarin extracted from the root of traditional Chinese medicine Qiang-Huo (Notopterygium incisum), had shown the antiproliferative and anti-inflammatory properties in previous studies, we hypothesized that it could play a role in ameliorating PAH.MethodsIn vivo, we conducted monocrotaline (MCT) induced PAH rats and treated them with notopterol for 3 weeks. Then, the rats were examined by echocardiography and RV catheterization. The heart and lung specimens were harvested for the detection of gross examination, histological examination and expression of inflammatory molecules. In vitro, human pulmonary arterial smooth muscle cells (HPASMCs) were treated with notopterol after hypoxia; then, cell proliferation was assessed by cell counting kit-8 and Edu assay, and cell migration was detected by wound healing assays.ResultsWe found that notopterol improved mortality rate and RV function while reducing right ventricular systolic pressure in MCT-induced PAH rats. Furthermore, notopterol reduced right ventricular hypertrophy and fibrosis, and it also eased pulmonary vascular remodeling and MCT-induced muscularization. In addition, notopterol attenuated the pro-inflammatory factor (IL-1β, IL-6) and PCNA in the lungs of PAH rats. For the cultured HPASMCs subjected to hypoxia, we found that notopterol can inhibit the proliferation and migration of HPASMCs.ConclusionOur studies show that notopterol exerts anti-inflammatory and anti-proliferative effects in the pulmonary arteries, which may contribute to prevention of PAH.

EFFECTS OF TRANSCUTANEOUS PERIPHERAL NERVE ELECTROSTIMULATION DEVICE FOR BLOOD PRESSURE CORRECTION

Objective: Currently the therapy of arterial hypertension (AH) is mainly based on antihypertensive medicines. The medical transcutaneous peripheral nerve electrostimulator “ABP-051’’ (“Shvabe’’&amp; “INFERUM’’, Russia) allows to influence the level of blood pressure (BP) in a non-drug way, but its effectiveness was tested only by comparing discrete blood pressure measurements. The aim of the study was to evaluate the effect of the course use of the stimulator “ABP-051’’ on the circadian blood pressure profile (CBPP), reconstructed according to three-day BP-monitoring in patients with hypertension. Design and method: Patients: the study included 62 patients with hypertension: AH patients with regular antihypertensive therapy, who were andomised into 2 groups: the main group of 52 patients who were treated by the “ABP-051’’ and 10 patients in control group with sham stimulation. Methods: all patients underwent a study of the dynamics of the level and profile of blood pressure by means assessment of CBPP (the method of non-sinusoidal variability) based on the reconstruction of three-day BP monitoring. Results: It was found that stimulation therapy is not accompanied by side effects and does not lead to significant fluctuations in blood pressure after a single procedure. During the course of therapy, a significant decrease in blood pressure and circadian profile indicators was observed in 66% of patients (fig.1). The average decrease in systolic blood pressure is -8.3 ± 7.7 mm Hg, diastolic blood pressure is 5.8 ± 3.8 mm Hg. The effect of the course treatment was observed by the end of the 2-week stimulation cycle and in most patients persisted for 2 weeks after its completion. In general, positive effects on the blood pressure profile were observed in 90% of patients, whereas there were no changes in the control group. Conclusions: The course use of “ABP-051’’ is safe and in 90% of patients with hypertension contributes to decrease of BP and/or the improvement of the circadian blood pressure profile.

Use of single pill combinations in the treatment of arterial hypertension in Poland: The current practice and guidelines, the impact on reimbursement spending and patient co-payment.

BackgroundClinical guidelines recommend using single pill combinations (SPC) when initiating and intensifying the treatment of arterial hypertension (AH), which is not reflected in the Summaries of Product Characteristics (SMPC) for individual preparations. The drug reimbursement system in Poland (with a few exceptions) does not provide for reimbursement outside the indications specified in the SMPC. Therefore, it excludes the use of SPC under reimbursement. In 2020 the share of SPC in the treatment of AH amounted to 12.8% of unit volume and was lower than the 80% based on the guidelines of the Polish Society of Hypertension.MethodsUsing the data from a sample of pharmacies in Poland over the period November–December 2020, the potential was assessed of switching from existing AH therapy with monocomponent drugs containing selected combinations of active ingredients to the equivalent SPC.ResultsThe potential of switching from AH treatment in the analyzed period using monocomponent drugs with the equivalent SPC amounted to 19% of unit volume (a reduction of 212M units), with the highest switch potential (43.9%) for drugs containing amlodipine. The public payer’s savings would be EUR 12.3 million and patient savings would amount to EUR 5.0 million.ConclusionsEnabling reimbursement of SPC in Poland in line with the clinical guidelines can significantly increase the share of SPC in the treatment of AH, which will result in better health outcomes and a significant reduction in the payer’s drug reimbursement spending and will lower the financial barrier for patients to access this type of treatment.