Azilsartan Research Articles

PP.22.13] EVALUATION OF EFFICACY AZILSARTAN MEDOXOMIL ON CENTRAL AORTIC BLOOD PRESSURE AND AMBULATORY BLOOD PRESSURE IN PATIENTS WITH MILD TO MODERATE ESSENTIAL HYPERTENSION

Objective: This study was aimed to evaluate the effect of azilsartan medoxomil (AZL) on central aortic blood pressure (CAP) and 24-hours blood pressure (BP) in grade 1 and 2 hypertensive patients. Design and method: Thirty nine patients (79% men, all white, mean age – 40 years) with mild to moderate essential hypertension, never treated before, were enrolled. Dose of AZL was gradually increased until maximum 80 mg once-daily. Follow-up of the study amounted to 6 months. CAP measurement (SphygmoCor CVMS, Atcor, Australia) and 24-hours blood pressure monitoring (ABPM, Meditech, Hungary) were measured before treatment and on the last visit. Results: Mean value (mean ± SEM) of baseline 24-hours systolic BP (SBP) was 142 ± 2,09 mm Hg and 24-hours diastolic BP (DBP) – 85 ± 2,14 mm Hg, while mean value of CAP was 137 ± 2,9 mm Hg. At the end of the study mean value of 24-hours SBP was 127.2 ± 1.2 mm Hg, 24-hours DBP – 75 ± 1.8 mm Hg and CAP was 119 ± 2,1 mm Hg. So decrease from baseline to final CAP, 24-hours SBP and 24-hours DBP were −18, −15 and −10 mm Hg respectively. An outcome of the study shows a significant reduction in both 24-hours SBP and DBP (p < 0.0001) and CAP changes (p < 0.005). Conclusions: Once-daily AZL effectively lowers CAP in adults with mild to moderate essential hypertension and has shown good antihypertensive efficacy according to 24-hours blood pressure monitoring as well.

Azilsartan ameliorates diabetic cardiomyopathy in young db/db mice through the modulation of ACE-2/ANG 1–7/Mas receptor cascade

Hyperglycemia up-regulates intracellular angiotensin II (ANG-II) production in cardiac myocytes. This study investigated the hemodynamic and metabolic effects of azilsartan (AZL) treatment in a mouse model of diabetic cardiomyopathy and whether the cardioprotective effects of AZL are mediated by the angiotensin converting enzyme (ACE)-2/ANG 1–7/Mas receptor (R) cascade. Control db/+ and db/db mice (n=5 per group) were treated with vehicle or AZL (1 or 3mg/kg/d oral gavage) from the age of 8 to 16weeks. Echocardiography was then performed and myocardial protein levels of ACE-2, Mas R, AT1R, AT2R, osteopontin, connective tissue growth factor (CTGF), atrial natriuretic peptide (ANP) and nitrotyrosine were measured by Western blotting. Oxidative DNA damage and inflammatory markers were assessed by immunofluorescence of 8-hydroxy-2′-deoxyguanosine (8-OHdG), tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). Compared with db/+ mice, the vehicle-treated db/db mice developed obesity, hyperglycemia, hyperinsulinemia and diastolic dysfunction along with cardiac hypertrophy and fibrosis. AZL treatment lowered blood pressure, fasting blood glucose and reduced peak plasma glucose during an oral glucose tolerance test. AZL-3 treatment resulted in a significant decrease in the expression of cytokines, oxidative DNA damage and cardiac dysfunction. Moreover, AZL-3 treatment significantly abrogated the downregulation of ACE-2 and Mas R protein levels in db/db mice. Furthermore, AZL treatment significantly reduced cardiac fibrosis, hypertrophy and their marker molecules (osteopontin, CTGF, TGF-β1 and ANP). Short-term treatment with AZL-3 reversed abnormal cardiac structural remodeling and partially improved glucose metabolism in db/db mice by modulating the ACE-2/ANG 1–7/Mas R pathway.

FORMULATION AND IN VITRO EVALUATION OF AZILSARTAN MEDOXOMIL NANOSUSPENSION

Objective: The objective of this study was to formulate and evaluate of the poorly soluble drug, azilsartan medoxomil into nanosuspension to increase the solubility and enhance the dissolution rate and then improve its bioavailability.Methods: Nanosuspension of azilsartan medoxomil was prepared using solvent-antisolvent precipitation method using PVP-K30 as a stabilizer. Eight formulations were prepared to show the effect of different parameters in which four formulations show the effect of stabilizer concentration, three formulations show the effect of stirring speed and two formulations prepare to show the effect of the addition of co-stabilizer such as sodium lauryl sulphate (SLS) and tween 80. All these formulation are evaluated for their particle size and entrapment efficiency. The selected one was evaluated for zeta potential, scanning electron microscope (SEM), saturation solubility, and in vitro drug release.Results: All the prepared formulations were in the nano size. The optimum concentration of the stabilizer was in the formulation when the drug: stabilizer ratio 1:1 and optimum stirring speed was 300 rpm. Dramatic effect on the particle size reduction was found by the addition of co-stabilizer (SLS) in formulation F3 that has P. S 157±0.0 nm. The selected formula F3 showed an enhanced dissolution profile compared to the pure drug at all-time intervals.Conclusion: The results show that the formulation that contain drug: PVP-K30: SLS in ratio 1:0.75:0.25 is the best one and can be utilized to formulate azilsartan medoxomil nanosuspension.

Azilsartan Medoxomil, an Angiotensin II Receptor Antagonist for the Treatment of Hypertension.

Azilsartan (AZL) medoxomil was approved by the United States Food and Drug Administration in 2011 for the treatment of hypertension and has shown promising results both in blood pressure (BP) reduction and in tolerability, but has not yet been taken into practice to the same extent as other angiotensin II receptor blockers (ARBs) that have been on the market for a longer period. AZL antagonizes the AT1 receptor for angiotensin II (ANG II), whereas angiotensin-converting enzyme inhibitors block the conversion of angiotensin I to ANG II, but not alternative routes of formation of ANG II. The bioavailability of AZL is about 60% and it has a tmax of 1.5-3hr and a half-life of approximately 11hr. With its IC50 of 7.4nM after 5hr of drug washout in radioligand assays, AZL has a tighter and longer-lasting binding to the AT1 receptor by several orders of magnitude than other ARBs, which might lead to a more effective reduction in BP. Clinical studies have revealed that AZL doses of 40 and 80mg/day reduce BP significantly better than maximal clinical doses of valsartan or olmesartan, while being well tolerated and exhibiting a spectrum of adverse effects comparable to those of other ARBs. These properties of AZL might lower the risk of cardiovascular disease and thereby reduce mortality rates. However, the existing mortality studies have not found this correlation, which should be further investigated.

Advantages azilsartan medoxomil in patients with arterial hypertension: how to make a choice and to optimize antihypertensive therapy?

Azilsartan medoxomil is a drug from class of angiotensin II receptor antagonist (sartans), have a antihypertensive effect and excellent tolerability profile. In comparison with other drugs (candesartan, olmesartan, ramipril, chlorthalidone, valsartan) according to comparative studies and meta-analyses azilsartan medoxomil demonstrated high antihypertensive efficacy, in terms of 24-hour BP control, which allows to recommend its purpose in patients of hypertension 1-2 degrees. This is due to the ability of the drug not only safely reduce AD during day and night hours, but also to normalize the circadian profile. Pleiotropic effects of azilsartan medoxomil in the form of increased sensitivity of receptors to insulin, a positive effect on glucose metabolism, improved endothelial function allow us to consider its purpose in patients with carbohydrate metabolism disorders, overweight, obesity, and metabolic syndrome. The drug is indicated for as patients who have not previously received antihypertensive therapy and if previous treatment with other RAAS blockers did not lead to reliable achievement of target BP levels. High efficiency and safety of azilsartan medoxomil can provide better patient adherence to long term therapy and achieve optimal results of therapy.

Reliable and Sensitive Stability Indicating – Liquid Chromatographic Method for Determination of Azilsartan Medoxomil and Characterization of Common Hydrolytic Degradation Product

Objective: The objective of the proposed method was to develop an accurate, rapid and cost-effective stability indicating a reversed phase high-performance liquid chromatographic method for the determination of azilsartan medoxomil. Materials and Methods: Chromatographic separation of the analyte from its degradation products was achieved on Qualisil- Gold column with a mobile phase composition of Acetonitrile and 0.2% Triethyl amine[pH 3.0], [62:38%v/v] at flow rate was 1.0 ml/min, the eluents were monitored using PDA detector at 248 nm. Results: The method was linear (r2 = 0.9997) in the concentration range of 20-120 μg/ml with acceptable percentage relative standard deviations for Inter-day (0.22 %) and Intraday (0.31 %) precisions. The result for accuracy study was 99.92-100.29 %. Conclusion: The method has proven specificity to quantify azilsartan medoxomil in presence of its degradation products formed in stress studies. Five major degradation products were found in stress studies, among them impurity-4 was identified and it was also observed that the drug was more susceptible to thermal and photolytic degradations. Key words: Stability indicating assay, Azilsartan medoxomil, RP-HPLC, ICH guidelines, Forced Degradation, Validation.

Development Using Response Surface Methodology and Validation of a Stability-Indicating RP-HPLC Method for Simultaneous Estimation of Azilsartan Medoxomil and Chlorthalidone in Solid Dosage Form

A stability-indicating reversed-phase high-performance liquid chromatography method using a photodiode array detector has been developed for simultaneous estimation of chlorthalidone (CLR) and azilsartan medoxomil (AZL) in combined solid dosage form. The method was developed based on statistical design of experiments (DoE) followed by optimization using the response surface methodology. Separation was achieved on a double end-capped C18 column (150 mm × 4 mm, 5 µm). The effects of % acetonitrile (v/v) and buffer salt concentrations on the retention time of the two drugs and on their resolution were investigated and optimized. A robust design space was created by the overlay contour plot method. The optimum chromatographic condition within the design space was found to be isocratic mobile phase consisting of 10 mM Tris(hydroxymethyl)aminomethane buffer (pH 7.7) and acetonitrile at ratio of 60:40 (v/v) with flow rate of 1 mL min−1 for 7 min. The retention times of CLR and AZL were found to be 2.6 and 4.9 min, respectively. The method was validated according to International Conference on Harmonization (ICH) and Food and Drug Administration (FDA) guidelines, and various validation parameters were determined. Forced degradation studies were also carried out in acid, base, oxidation, and reduction media with a view to establishing the specificity and stability-indicating property. The practical applicability of the method was confirmed by determining CLR and AZL in combined dosage form. This reliable and validated stability-indicating method for simultaneous estimation of CLR and AZL is available for routine analysis in the pharmaceutical industry as well as research laboratories.

Solvent effect on the self-assembly of salt solvates of an antihypertensive drug azilsartan and 2-methylimidazole

Three salt solvates of azilsartan (AZ) with 2-methylimidazole (2MI) (namely AZ-2MI-H2O, AZ-2MI-ACE and AZ-2MI-THF) and one azilsartan solvate (AZ-DIO, ACE = acetone, THF = tetrahydrofuran, and DIO = 1,4-dioxane) were manufactured by solvent-controlled self-assembly in aqueous-organic solutions. The experimental result of AZ-DIO shows that AZ is high affinity to DIO molecule, which has a unique ability to prevent salt formation between AZ and 2MI. Thermal studies of three salt solvates exhibit poor thermodynamic stability in environmental conditions. Solubility experiments show that AZ-2MI-ACE and AZ-2MI-THF are unstable and convert to AZ-2MI-H2O in aqueous solution, and that AZ-2MI-H2O exhibits increased solubility and retention stability in an aqueous medium compared with the commercial AZ-A crystalline form.

EFFICACY OF AZILSARTAN MEDOXOMIL ON THE DAILY PROFILE OF PERIPHERAL AND CENTRAL ARTERIAL PRESSURE AND ARTERIAL STIFFNESS IN HYPERTENSIVES WITH TYPE 2 DIABETES

Comorbidity of diabetes mellitus (DM) with arterial hypertension (AH) leads to four-time increase of cardiovascular risk (CVR). Achievement of target blood pressure (BP) is one of the main strategies of cardiovascular complications prevention in DM patients. Efficacy of azilsartan medoxomil is higher than of other drugs from the group. Aim. To study changes in peripheral and central BP daily profile and parameters of arterial stiffness in replacement of RAAS blocker as a part of two component antihypertension therapy (AHT) by 40 mg azilsartan medoxomil for patients with AH and type 2 DM, with dose titration to 80 mg if target BP not reached. Material and methods . Thirty AH+DM2 patients not having target BP<140/85 mmHg on two component AHT (53% females, mean age 60,4±7,6 y.o., 40% smokers). Replacement of RAAS blocker by azilsartan medoxomil 40 mg with dose increase to 80 mg in 6 weeks if BP <140/85 mmHg not achieved. Folow-up lasted for 12 weeks. 24-hour profile of peripheral and central BP and parameters of arterial stiffness were assessed with BPLab Vasotens (JSC “Piotr Telegin”). The results were statistically significant in p<0,05. Results. In 12 weeks of therapy, 25 patients (83%) reached the target peripheral BP<140/85 mmHg. The increase of azilsartan medoxomil at week 6 was needed in 11 (37%) patients. In 12 weeks there was significant decrease in clinical peripheral and central BP (from 160±16/89±9 mmHg to 125±7/73±6 mmHg and from 144±11/84±4 mmHg to 115±9/67±5 mmHg, respectively), decrease of the mean daily peripheral BP by 22/9 mmHg, central by 18/13 mmHg, mean nocturnal BP by 24/9 mmHg and 19/10 mmHg, respectively. There was significant decrease of daily and night variability of SBP (from 15±4 to 10±3 mmHg and from 11±3 to 8±2 mmHg, resp.), decrease of PWV (from 10,2±2,3 to 9,5±2,2 m/s) and augmentation index (from 24,6±8,6 to 13±7,0%), р<0,05 for all differences. There were no significant changes in PP amplification. Improvement of 24-hour BP (ABPM) led to increase of the dippers portion: improvement of SI SBP at azilsartan medoxomil was found in 53% cases. There was decrease of the level of morning SBP raise: from 34±13 mmHg to 25±10 mmHg (р<0,05). The drug demonstrated metabolic neutrality and good tolerability. Conclusion. Replacement of RAAS by azilsartan medoxomil in AH and DM2 patients taking bicomponent AHT leads to achievement of target clinical BP in 83% of patients, normalization of 24-hour profiles of peripheral and central BP and improvement of parameters of arterial stiffness in most patients. Azilsartan medoxomil therapy tolerated good and is metabolically neutral.

Преимущества азилсартана медоксомила у пациентов с артериальной гипертонией: как правильно осуществить выбор и оптимизировать антигипертензивную терапию?

Azilsartan medoxomil is a drug from class of angiotensin II receptor antagonist (sartans), have a antihypertensive effect and excellent tolerability profile. In comparison with other drugs (candesartan, olmesartan, ramipril, chlorthalidone, valsartan) according to comparative studies and meta-analyses azilsartan medoxomil demonstrated high antihypertensive efficacy, in terms of 24-hour BP control, which allows to recommend its purpose in patients of hypertension 1-2 degrees. This is due to the ability of the drug not only safely reduce AD during day and night hours, but also to normalize the circadian profile. Pleiotropic effects of azilsartan medoxomil in the form of increased sensitivity of receptors to insulin, a positive effect on glucose metabolism, improved endothelial function allow us to consider its purpose in patients with carbohydrate metabolism disorders, overweight, obesity, and metabolic syndrome. The drug is indicated for as patients who have not previously received antihypertensive therapy and if previous treatment with other RAAS blockers did not lead to reliable achievement of target BP levels. High efficiency and safety of azilsartan medoxomil can provide better patient adherence to long term therapy and achieve optimal results of therapy.

Development of RP-HPLC method for separation of atorvastatin calcium, amlodipine besylate and azilsartan medoxomil and its application to analyze their tablet dosage forms

Development of RP-HPLC method for separation of atorvastatin calcium, amlodipine besylate and azilsartan medoxomil and its application to analyze their tablet dosage forms

MODERN OPPORTUNITIES FOR ANTIHYPERTENSION THERAPY: THE PLACE OF AZILSARTAN MEDOXOMIL

Modern approaches to antihypertension therapy suppose the usage of combination drugs, making significant positive influence on the values of systemic blood pressure (BP) in daily and nocturnal periods, optimization of 24-hour BP profile, achieved target BP in most of patients. Also, it is important to fulfill organ protection and vessel protection. To all these criteria does respond azilsartan medoxomil and its combination with chlorthalidone. The combination azilsartan/chlorthalidone shows serious antihypertension properties, including the patients with metabolic disorders, facilitates optimization of BP at night, decrease of vascular stiffness. Collection of positive properties of the combination makes it to apply broadly in real clinical practice to increase efficacy of hypertension patient’s management.

COMBINATION OF AZILSARTAN MEDOXOMIL AND CHLORTHALIDONE: IS IT POSSIBLE TO FIGHT SYSTEMIC HYPERTENSION AND OBESITY TOGETHER?

Arterial hypertension (AH) and obesity are the main risk factors of chronic noncommunicable diseases. Adipous tissue is not only a depot for energetic compounds, but is an active endocrine organ synthetizing biologically active substances that facilitate development of AH. Patients with AH and obesity are in the high cardiovascular risk group and demand effective combination antihypertension therapy. One of such drugs is the fixed combination of azilsartan medoxomil and chlorthalidone, which safety and efficacy are confirmed by various trials. Our clinical case demonstrates positive action of Edarbi Сlo on office and 24-hour blood pressure (BP), main parameters of aorta stiffness and structural and functional condition of myocardium at rest, as in exertion in patient with AH and obesity.

Optimization, characterization and in vitro/vivo evaluation of azilsartan nanocrystals

Azilsartan (AZL), a poorly soluble drug, was considered to be fit for nanocrystals to improve its solubility. Our study intended to prepare AZL nanocrystals by means of bead milling method. Eight stabilizers or their binary combination and the milling time were set to be variable factors to optimize AZL nanosuspension formulation, and six types of freeze-drying supports were investigated to reduce the aggregation of particles during the solidification. AZL nanocrystals with or without sodium deoxycholate (NaDC) as combined stabilizer with Poloxamer 188 (F68) were prepared owning mean particle sizes of about 300 nm and 460 nm. During the screening processes, the formulation containing NaDC showed a smaller particle size and better stability during lyophilization. The irregular shape and crystal form changing in AZL nanocrystals were discovered by various characterizations. And with physical mixture as reference, nanocrystals showed its improvement about in-vitro dissolution and in-vivo bioavailability. In conclusion, the nanocrystals of AZL could be prepared well in our study. Additionally, our results suggested that NaDC was an appreciated excipient on the nanocrystals platform, which can exhibit the abilities of size-reduction and stability-maintaining on freeze-drying.

Hronotherapy Aspects of Efficiency Azilsartan Medoxomil in Combination Therapy in Patients With Hypertension and Metabolic Syndrome

Determination of the effectiveness and safety of different dosing regimens during the day (in the morning or at bedtime) combination therapy including azilsartan medoxomil in patients with essential hypertension and metabolic syndrome (MS). The study included 60 patients with uncontrolled hypertension and MS (age median - 59 (54-65) years). Patients were randomized in two groups: group 1 (n=30) received azilsartan medoxomil 40 mg/day, and indapamide retard 1,5 mg/day in the morning; group 2 (n=30)- azilsartan medoxomoil 40 mg at bedtime and indapamide retard 1,5 mg in the morning. All patients at baseline, and after 4 and 12weeks assessed levels of office blood pressure (BP), heart rate (HR); at baseline and after 12 weeks was conducted ambulatory BPmonitoring (ABPM). Evaluated the main indicators of circadian blood pressure profile, as well as the central aortic pressure (CAP) and the rigidity of the vascular wall: systolic, diastolic, and mean arterial pressure in the aorta, aortic augmentation index, pulse wave velocity in the aorta, the augmentation index. Study results were processed using the program Statistica 6.1 by methods nonparametric statistics. Regardless of the regimen used azilsartan destination as part of combination therapy after 4 weeks showed a significant (p<0.05) reduction in SBP and DBP. After 12 weeks of observation target blood pressure was recorded 27 (90%) patients of group 1 and 29 (96.7%)- group2. As a result of ABPM after 12 weeks of treatment in both groups showed a statistically significant (p<0.05) improvement in all parameters investigated. However, positive changes such indicators as an index time of hypertension in the day and night hours, SBP, DBP, and BP variability during the night, the morning rise of systolic as well as the speed of morning rise in SBP and DBP were more pronounced in the appointment azilsartan medoxomil at bedtime compared to morning reception. The use of both treatment regimens provided significant (p<0.05) increase frequency registration profile dippear and reduction - non-dipper. Importantly, irrespective of the time of taking the drugs in both groups occurred significant (p <0.05), and a comparable improvement in rigidity and CAP vascular wall. When combined with essential hypertension and MS azilsartana use of combination drug therapy provided achievement of the target values of blood pressure in the majority of patients, a significant improvement in the main indicators of ABPM, CAP, and the rigidity of the vascular wall, as well as the normalization of daily profile of blood pressure in the majority of patients, regardless of dosing regimen during the day. However, the combination of indapamide retard morning - azilsartan medoxomil at bedtime accompanied by a significantly greater positive changes most ABPM parameters, especially at night.

Polymorphs and solvatomorphs of azilsartan medoxomil: Elucidation of solvent-induced construction and conformational diversity

Two polymorphs (AM-A and AM-B) of azilsartan medoxomil (AM) and four AM solvatomorphs with toluene (AM-TOL), 1,4-dioxane (AM-DIO), chloroform (AM-TCM) and N,N-dimethylacetamide (AM-DMA) have been prepared by the hydrolysis of azilsartan medoxomil potassium in aqueous-organic solutions. In the crystal structures of two polymorphs and three solvatomorphs (AM-TOL, AM-DIO and AM-TCM), two asymmetric AM molecules form the dimeric cycle-like structures via intermolecular NH⋯N hydrogen bonds in R22 (26) ring, while AM-DMA shows intramolecular NH⋯O hydrogen bond between AM and DMA molecules. The hydrogen bonds (CH⋯O or CH⋯N) and π···π (or CH···π) interactions are helpful to stabilize the conformational diversity of AM. The solvent-induced experiment shows that solvent molecules have great influence on the solvatomorph formation and DIO can form the most steady solvatomorph than other solvents. The thermal study demonstrates that toluene molecules in three solvatomorphs (AM-TOL, AM-DIO and AM-TCM) are the most difficult to remove from the cage. Our results illustrate that the solvent plays significant role in tuning the size of the cage and producing the conformational diversity of AM molecules.

GW27-e0799 Safety of azilsartan medoxomil in hypertension: A Meta-analysis

This study was to compare the safety in patients with hypertension receiving azilsartan medoxomil as monotherapy or other antihypertensive agents. The Cochrane library, PubMed, Chinese National Knowledge Infrastructure(CNKI), Wanfang Data were searched from the beginning of the records through

The possibility of a new receptor blocker to angiotensin in improving control of hypertension. Non-intervention international multicenter observational prospective study of the use azilsartan medoxomil in patients with arterial hypertension and overweight or obesity in the Russian Federation and the Republic of Kazakhstan

Currently, there is evidence of a rather low efficacy of antihypertensive therapy, especially in patients with obesity and metabolic disorders that indicate the need for the search of new highly effective antihypertensive agents that have additional features to prevent destruction of target organs and cardiovascular complications. On the Russian pharmaceutical market antihypertensive drugs presents receptor blocker to angiotensin - azilsartan medoxomil (Edarbi®). The article is published design of study of the effectiveness of azilsartan medoxomil in patients with arterial hypertension and overweight or obesity in daily clinical practice of the Russian Federation and the Republic of Kazakhstan.

PS 14-35 INFLUENCE OF AZILSARTAN MEDOXOMIL ON CENTRAL AORTIC BLOOD PRESSURE AND AMBULATORY BLOOD PRESSURE IN PATIENTS WITH MILD TO MODERATE ESSENTIAL HYPERTENSION

Objective: This study was planned to assess influence of azilsartan medoxomil (AZL) on central aortic blood pressure (CAP) and 24-hours blood pressure (BP) in patients with mild to moderate hypertension. Design and Method: Twenty-nine patients (75% men, all white, mean age – 43 years) with mild to moderate essential hypertension, never treated before, were enrolled. Dose of AZL was gradually increased until maximum 80 mg once-daily. Follow-up of the study amounted to 6 months. CAP measurement (SphygmoCor CVMS, Atcor, Australia) and 24-hours blood pressure monitoring (ABPM, Meditech, Hungary) were measured before treatment and on the last visit. Results: Mean value (mean ± SEM) of baseline 24-hours systolic BP (SBP) was 144 ± 1.8 mmHg and 24-hours diastolic BP (DBP)–85 ± 1.6 mmHg, while mean value of CAP was 139 ± 2.9 mmHg. At the end of the study mean value of 24-hours SBP was 128 ± 1.9 mmHg, 24-hours DBP–77 ± 2.1 mmHg and CAP was 121 ± 3,0 mmHg. So decrease from baseline to final CAP, 24-hours SBP and 24-hours DBP were −18, −16 and −8 mmHg respectively. An outcome of the study shows a significant reduction in both 24-hours SBP and DBP (p < 0.0001) and CAP changes (p < 0.005). Conclusions: Once-daily AZL effectively lowers CAP in adults with mild to moderate essential hypertension and has shown good antihypertensive efficacy according to 24-hours blood pressure monitoring as well.

PP.05.13] AZILSARTAN MEDOXOMIL PROPORTIONALLY DECREASES CENTRAL AND BRACHIAL 24-H AMBULATORY BLOOD PRESSURE IN DIABETIC PATIENTS WITH DIFFICULT-TO-CONTROL ARTERIAL HYPERTENSION

Objective: Ambulatory monitoring of central blood pressure (BP) and arterial stiffness is a new technique for evaluation of antihypertensive drugs efficacy. The aim of the study was to assess changes in ambulatory brachial and central BP and AIx after azilsartan medoxomil (AM) 40 mg adjunction to treatment regimen in hypertensive type 2 diabetic patients. Design and method: AM 40 mg was given as substitution drug to ACEi to 20 hypertensive patients (8 male, age 58 + 10 years) with clinic BP >140/90 mmHg, 24-h BP >130/80 mmHg and/or daytime BP>135/85 mmHg previously treated with an ACEI and a second drug from another class. ABPM was done with BPLab VASOTENS (OOO Petr Telegin, Nizhniy Novgorod, Russia). Brachial and aortic BP changes as well as changes in 24-h, day- and nighttime AIx were evaluated. p < 0,05 was considered significant. Results: Significant (p < 0,05 vs baseline) decrease in 24-h, day- and nighttime BP after 4 weeks of Azilsartani medoxomil adjunction was observed: for brachial SBP, respectively, from 150 + 10 to 134 + 8, from 150 + 10 to 134 + 10, from 148 + 15 to 132 + 12 mmHg, for brachial pulse pressure (PP) from 54 + 10 to 48 + 9, from 54 + 8 to 46 + 8, from 56 + 10 to 48 + 7 mmHg. For aortic SBP corresponding changes were from 139 + 10 to 126 + 9, from 140 + 10 to 126 + 8, from 138 + 12 to 128 + 10 mmHg, for aortic PP, respectively, 46 + 6 to 38 + 5, from 44 + 6 to 36 + 8, from 46 + 7 to 38 + 6 mmHg. AIxHR75 bpm decreased at daytime from 28,3 + 12,6 to 21,7 + 10,1%, at night-time from 32,2 + 10 to 26 + 9%. Increase in PP amplification was observed also and was more evident in nighttime: baseline difference between brachial and aortic PP was 10,0 + 3,2 for daytime, 10,0 + 3,2 mmHg for nighttime, after azilsartan medoxomili treatment 10,7 + 2,6 and 10,2 + 2,8 mmHg, respectively (p < 0,05). Conclusions: Azilsartan medoxomil decreases significantly either brachial or aortic SBP and PP, as well decreases aortic PP augmentation. In hypertensive diabetic patient PP amplification was similar at day- and nighttime before and after treatment meaning proportional decrease of brachial and central SBP and PP.