tak-491 and Obesity

Arterial hypertension (AH) is one of the most common cardiovascular disease. Angiotensin II (AT II), the hormone of renin-angiotensin-aldosterone system, realizes its negative effects through AT 1 receptors - application point of angiotensin receptor blockers (ARB). Due to different dissociation AT 1 receptors properties some ARBs are more effective than others. Multiply multicenter randomized and observational studies approve the effectiveness and safety of azilsartan medoxomil in patients with AH 1-2 grade. Several preclinical studies have shown the additional properties of azilsartan, including increase of insulin sensitivity, cardio- and nephron protection in obesity. In our clinical case we showed the positive influence of azilsartan medoxomil on clinic and ambulatory blood pressure, 24-hour aortic stiffness parameters, longitudinal left ventricular strain in patient with AH and obesity.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Humans; Hypertension; Male; Obesity; Oxadiazoles

To assess the influence of the therapy of arterial hypertension with azilsartan medoxomil on the renal function in overweight or obese patients with concomitant metabolic disorders.. An international multicenter observational nonintervention prospective study included 1945 patients, taking azilsartan medoxomil in accordance with approved prescribing information. The observation period reached 6 months.. In patients with an initial glomerular filtration rate (GFR)60 ml/min/1.73 m2 or 60 ml/min/1.73 m2 mean change in systolic blood pressure after 6 months of therapy reached -32.511.1 and -30.413.6 mmHg, correspondingly, while the change in diastolic blood pressure was -13.78.8 and -14.29.4 mmHg, respectively. No decrease in renal function was observed. Moreover, in patients with an initial GFR60 ml/min/1.73 m2 GFR increased significantly (p0.001).. Azilsartan medoxomil, prescribed as monotherapy or in free combinations, provided an effective control of blood pressure in patients with arterial hypertension with both normal or moderately reduced and initially significantly reduced renal function. High efficacy and acceptability of the drug was associated with a beneficial effect on renal function, which allows to consider azilsartan medoxomil as the drug of choice for the treatment of hypertension in patients with concomitant metabolic disorders.. Цель. Оценить влияние антигипертензивной терапии азилсартана медоксомилом на динамику функционального состояния почек у пациентов с избыточной массой тела или ожирением и сопутствующими метаболическими нарушениями. Материалы и методы. Оценено состояние функции почек у 1945 пациентов, включенных в международное многоцентровое наблюдательное неинтервенционное проспективное исследование с применением азилсартана медоксомила в соответствии с утвержденной инструкцией по использованию препарата. Период наблюдения составил 6 мес. Результаты. Выделены 2 группы пациентов в зависимости от исходной скорости клубочковой фильтрации (СКФ): 1-я группа с СКФ60 мл/мин/1,73 м2 и 2-я с СКФ60 мл/мин/1,73 м2. В обеих группах пациентов среднее изменение систолического артериального давления через 6 мес терапии достигло -32,511,1 и -30,413,6 мм рт. ст. соответственно, а изменение диастолического артериального давления -13,78,8 и -14,29,4 мм рт. ст. соответственно. В результате исследования не отмечено ухудшения функции почек на фоне терапии азилсартана медоксомилом. Более того, у пациентов с исходной СКФ60 мл/мин/1,73 м2 установлено статистически значимое увеличение СКФ по сравнению с исходными показателями (p0,001). Заключение. Азилсартана медоксомил как в режиме монотерапии, так и в свободных комбинациях с другими антигипертензивными препаратами обеспечивает эффективный контроль артериального давления у пациентов с артериальной гипертонией и метаболическими нарушениями как при нормальной или умеренно сниженной, так и при исходно значительно сниженной функции почек. Высокая эффективность и хорошая переносимость препарата сочетаются с нефропротективным действием, что позволяет рассматривать азилсартана медоксомил как препарат выбора для терапии артериальной гипертонии у пациентов с сопутствующими метаболическими нарушениями и сниженной функцией почек.

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Kidney; Metabolic Diseases; Obesity; Overweight; Prospective Studies; Tetrazoles; Treatment Outcome

Control of arterial hypertension in obese or overweight patients is complicated since obesity directly contributes to increased blood pressure, requiring new, highly effective antihypertensive drugs. This study evaluates the efficacy of azilsartan medoxomil in real clinical practice.. An international multicenter observational non-interventional prospective study of azilsartan medoxomil was conducted in 64 clinical centers in the Russian Federation and 5 centers in the Republic of Kazakhstan. This study included 1945 obese or overweight patients with arterial hypertension. Azilsartan medoxomil was prescribed in accordance with the approved instruction for use. The decision to prescribe the drug, dose adjustment and monitoring target BP achievement belonged to the attending physicians according to their routine clinical practice. The observation period took about 6 months.. The average duration of taking the medicine was 26.1 ± 4 weeks. By the fourth visit, the use of azilsartan medoxomil either in a monotherapy regimen or in free combinations resulted in a pronounced decrease in systolic and diastolic blood pressure by 30.5 ± 13.4 and 14 ± 9.4 mmHg, respectively (. Over the study time of 1945 patients, significant changes in blood pressure levels over time were noted, and a high frequency of response to the azilsartan therapy was observed. Adverse events related to the study drug were of mild or moderate intensity and did not require discontinuation of therapy. Thus, azilsartan medoxomil demonstrated a good safety profile and provided effective blood pressure control for overweight or obese patients with hypertension in real clinical practice.

Topics: Antihypertensive Agents; Benzimidazoles; Blood Pressure; Humans; Hypertension; Internationality; Male; Middle Aged; Obesity; Oxadiazoles; Prospective Studies

Angiotensin II type 1 receptor blockers (ARBs) are widely used in treating hypertension. In the present study, we tested the hypothesis that a novel ARB, azilsartan medoxomil (AZL-M) will prevent renal and cardiovascular injury in the spontaneously hypertensive obese rat (SHROB), a model of cardiometabolic syndrome.. Male SHROB were treated with vehicle or AZL-M orally for 56 days. Vehicle treated normotensive Wistar-Kyoto (WKY) rats served as controls. The effects of AZL-M on kidney injury, vascular endothelial and heart functions, lipid profile, and glucose tolerance were assessed.. AZL-M demonstrated anti-hypertensive effects along with markedly improved vascular endothelial function in SHROB. In these rats, AZL-M demonstrates strong kidney protective effects with lower albuminuria and nephrinuria along with reduced tubular cast formation and glomerular injury. AZL-M treatment also improved left ventricular heart function, attenuated development of left ventricular hypertrophy, and reduced cardiac fibrosis in SHROB.. Overall, these findings demonstrate kidney and heart protective effects of AZL-M in SHROB, and these effects were associated with its ability to lower blood pressure and improve endothelial function.

Topics: Animals; Antihypertensive Agents; Benzimidazoles; Blood Glucose; Body Weight; Cholesterol; Disease Models, Animal; Heart; Hypertension; Hypertrophy, Left Ventricular; In Vitro Techniques; Insulin; Kidney; Male; Mesenteric Arteries; Myocardium; Obesity; Oxadiazoles; Protective Agents; Rats, Inbred WKY; Triglycerides; Vasodilation

Topics: Animals; Antihypertensive Agents; Benzimidazoles; Hypertension; Male; Obesity; Oxadiazoles; Protective Agents

Angiotensin II receptor blockers (ARBs) are used widely for the treatment of heart failure. However, their use in obese and insulin-resistant patients remains controversial. To clarify their potential efficacy in these conditions, we administered azilsartan medoxomil (azilsartan), a prodrug of an angiotensin II receptor blocker to mice fed a high-fat diet (HFD) with left ventricular (LV) pressure overload (aortic banding). LV fibrosis (hydroxyproline), cardiac plasminogen activator inhibitor-1 (PAI-1; a marker of profibrosis), and creatine kinase (a marker of myocardial viability and energetics) were assessed. LV wall thickness and cardiac function were assessed echocardiographically. Mice given a HFD were obese and insulin resistant. Their LV hypertrophy was accompanied by greater LV PAI-1 and reduced LV creatine kinase compared with normal diet controls. Drug treatment reduced LV wall thickness, hypertrophy, and PAI-1 and increased cardiac output after aortic banding compared with results in HFD vehicle controls. Thus, azilsartan exerted favorable biological effects on the hearts of obese insulin-resistant mice subjected to LV pressure overload consistent with its potential utility in patients with analogous conditions.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Cardiac Output; Creatine Kinase; Diet, High-Fat; Echocardiography; Heart Ventricles; Hypertrophy, Left Ventricular; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Obesity; Oxadiazoles; Plasminogen Activator Inhibitor 1; Ventricular Pressure

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Insulin Resistance; Male; Obesity; Oxadiazoles