Azilsartan Research Articles

Efficacy and safety of azilsartan medoxomil in various doses in patients with metabolic disorders

Background. Obesity is an independent risk factor of the cardiovascular complications in patients with arterial hypertension (HTN). It can directly contribute to an increase in blood pressure (BP). Thus, the treatment of patients with HTN and obesity becomes a complex clinical problem, which requires new highly effective antihypertensive drugs.
 Aim. To assess the effectiveness and safety of novel angiotensin II receptor blocker azilsartan medoxomil (AZL-M) as monotherapy and in free combinations with diuretics and/or calcium antagonists in obese or overweight patients with HTN in real clinical practice.
 Materials and methods. An international multicenter observational non-interventional prospective study of the efficacy and safety of AZL-M in patients with hypertension and overweight or obesity was performed in the Russian Federation and the Republic of Kazakhstan. Patients took the drug for 6 months in accordance with the approved local instructions for use. All examinations were performed in accordance with routine clinical practice on the basis of a physicians decision.
 Results. In patients prescribed AZL-M as monotherapy (without dosage changes during the study) a significant decrease in systolic and diastolic blood pressure (systolic BP and diastolic BP, respectively) was observed (p0.001, compared to baseline); the average decrease in systolic BP and diastolic BP was 30.5012.67 and 14.478.65 mmHg, respectively (n=865). Target BP (140/90 mmHg or 140/85 mmHg in patients with diabetes mellitus) was achieved in 112 (94.12%), 547 (92.24%) and 135 (88.24%) of patients who were prescribed AZL-M at doses of 20, 40, or 80 mg/day, correspondingly. In patients receiving AZL-M in combination with a diuretic or calcium antagonist, the rate of achievement of ad blood pressure targets was 78.887.5% and 81.385.5%, respectively, and the frequency of response to therapy was 68.892.9% and 81.393.9%, respectively. During the entire observation period, 43 adverse events (AEs) were recorded, the most common of which were arterial hypotension (14 cases). All AEs associated with the study drug were of mild or moderate intensity.
 Conclusion. AEs administered as monotherapy and as part of combination therapy provided a statistically and clinically significant decrease in BP and a high frequency of target BP achievement in patients with HTN and metabolic disorders associated with overweight or obesity. Given the high efficacy and good tolerance of the drug, AEs can be considered as the drug of choice for the treatment of HTN in patients with overweight or obesity.

Are the Newest Angiotensin Receptor Blockers Preferred than the Old Members in COVID-19 Patients with Cardiovascular Comorbidity?

Background and Objective: The cardiovascular diseases are the most frequent comorbidities of Covid-19 infection. The severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) employs the angiotensin converting enzyme 2 (ACE2) receptor to invade cells. Angiotensin receptor blockers (ARBs) do not directly interact with ACE2 receptor, but they could affect course of Covid-19 infection because they increase expression of ACE2 and this could offer more binding sites for the virus. However, this could support cardiopulmonary protective effects of the ACE2/Ang-(1-7)/Mas axis. Also, sensitivity of an individual to COVID-19 infection might be affected by ACE2 polymorphism. To my knowledge, there are no clinical data to explain whether use of ARBs in COVID-19 patients with cardiovascular diseases is the same for all members or that some ARB members are preferred than others? This review tries to shed light on this issue. Materials and Methods: Wide literature search using many key words related to ARBs and COVID-19. Results: The newest ARBs (Olmesartan medoxomil and Azilsartan medoxomil) block the angiotensin II receptor 1 (AT1R) with inverse agonist activities, have no antagonistic effects on AT2R, upregulate ACE2 and stimulate ACE2/Ang-(1-7)/Mass receptor pathway. They are poor activators of peroxisome proliferator-activated receptor-γ (PPARγ) whose activation is not needed for their metabolic benefits. In addition, Olmesartan medoxomil inhibits ACE and decreases the plasma level of angiotensin II. Conclusion: In spite of their favorable pharmacological profiles, there is no enough evidence to support choice of the newest ARBs rather than the old ones for treatment of cardiovascular morbidities in COVID-19 patients.

Azilsartan medoxomil: opportunities and prospects in diabetes mellitus

Current data on the prevalence of hypertension and diabetes mellitus (DM) are presented. Concomitant DM complicates the course of cardiac diseases, affecting the effectiveness of antihypertensive therapy. Along with high blood pressure, lipid and carbohydrate metabolism parameters should be corrected. Nephroprotection is also important in these patients. These goals are achievable due to the pleiotropic effects of some drugs. The analytical paper reviews the pleiotropic organoprotective effects of the antihypertensive drug azilsartan medoxomil. The data on its antihypertensive efficacy versus other angiotensin II receptor blockers are presented. In addition, the results of clinical trials in patients with various components of the metabolic syndrome (obesity, dyslipidemia, hyperglycemia) and DM are described.

Full spectrum and genetic algorithm-selected spectrum-based chemometric methods for simultaneous determination of azilsartan medoxomil, chlorthalidone, and azilsartan: Development, validation, and application on commercial dosage form

Abstract Five various chemometric methods were established for the simultaneous determination of azilsartan medoxomil (AZM) and chlorthalidone in the presence of azilsartan which is the core impurity of AZM. The full spectrum-based chemometric techniques, namely partial least squares (PLS), principal component regression, and artificial neural networks (ANN), were among the applied methods. Besides, the ANN and PLS were the other two methods that were extended by genetic algorithm procedure (GA-PLS and GA-ANN) as a wavelength selection procedure. The models were developed by applying a multilevel multifactor experimental design. The predictive power of the suggested models was evaluated through a validation set containing nine mixtures with different ratios of the three analytes. For the analysis of Edarbyclor® tablets, all the proposed procedures were applied and the best results were achieved in the case of ANN, GA-ANN, and GA-PLS methods. The findings of the three methods were revealed as the quantitative tool for the analysis of the three components without any intrusion from the co-formulated excipient and without prior separation procedures. Moreover, the GA impact on strengthening the predictive power of ANN- and PLS-based models was also highlighted.

Is the newest angiotensin-receptor blocker azilsartan medoxomil more efficacious in lowering blood pressure than the older ones? A systematic review and network meta-analysis.

Angiotensin‐receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin‐receptor blockers may be more effective than the older ones. A network meta‐analysis was performed to compare the efficacy of various angiotensin‐receptor blockers in reducing office and ambulatory blood pressure in hypertensive patients. Relevant literature was searched from English and Chinese databases for randomized controlled trials involving angiotensin‐receptor blockers in hypertension. Efficacy variables included systolic and diastolic blood pressure either in the office or on ambulatory blood pressure monitoring. Absolute blood pressure reductions at 6‐12 weeks of treatment and their credible intervals were reported. A total of 34 publications provided adequate data for analysis (n = 14 859). In 28 studies on office systolic blood pressure (n = 12 731), against the common comparator valsartan 80 mg, the differences in systolic blood pressure were in favor of azilsartan medoxomil (20‐80 mg), irbesartan (300 mg), olmesartan (20‐40 mg), telmisartan (80 mg), and valsartan (160‐320 mg), but not candesartan (8‐16 mg), losartan (50‐100 mg), irbesartan (150 mg), olmesartan (10 mg), and telmisartan (40 mg). The ranking plot shows that azilsartan medoxomil 80 mg had a possibility of 99% being the best in the class. Similar results were observed for office diastolic blood pressure and from 13 studies for 24‐hour ambulatory systolic and diastolic blood pressure. In conclusion, angiotensin‐receptor blockers had different blood pressure lowering efficacy. The newest angiotensin‐receptor blocker azilsartan medoxomil at the dose of 80 mg seemed to be most efficacious in reducing both systolic and diastolic blood pressure in the office and on ambulatory measurement.

Efficacy and safety of using a fixed-dose combination of azilsartan medoxomil and chlorthalidone in patients with diabetes mellitus

All resent international and national guidelines for the treatment of patients with arterial hypertension offer a unified approach to the prescription of antihypertensive therapy. The vast majority of patients, including those with diabetes mellitus, require combined drugs. Renin-angiotensin-aldosterone system blockers, calcium channel blockers or diuretics are recommended as first-line therapy. The requirements for diuretics which can be used in this category of patients are especially strong. If patients with diabetes mellitus need diuretics as part of their antihypertensive therapy, thiazide-like diuretics should be preferred. Edarbi Clo, which is a fixed-dose combination of angiotensin receptor blocker azilsartan medoxomil and thiazide-like diuretic chlorthalidone met all these requirements. Along with its strong antihypertensive effect, Edarbi Clo has a beneficial effect on metabolism parameters, inflammation parameters and prevents damage to target organs, which makes it possible to recommend it as a drug of choice in this category of patients.

Evaluating the Safety and Tolerability of Azilsartan Medoxomil Alone or in Combination With Chlorthalidone in the Management of Hypertension: A Systematic Review.

Azilsartan medoxomil (AZM) is the newest representative in the class of angiotensin receptor blockers. Azilsartan medoxomil in combination with the older diuretic chlorthalidone (CLD) in fixed-doses of AZM/CLD 40/12.5 mg and 40/25 mg has been approved by the FDA for use in patients with essential hypertension. We sought to evaluate the safety and tolerability of AZL-M alone and in combination with CLD. We conducted a search in PubMed using the keywords 'azilsartan', 'azilsartan medoxomil', 'chlorthalidone, 'safety', 'tolerability' in order to find scientific studies evaluating the safety of these drugs. We included studies reporting side effects of these drugs, alone or in combination, in comparison to placebo or other antihypertensive medications. For our systematic review, we followed the PRISMA guidelines. Azilsartan medoxomil is a potent antihypertensive medicine with an acceptable safety profile. The most commonly reported adverse events are dizziness, headache, fatigue, upper respiratory tract infection and urinary tract infection. Chlorthalidone is more potent and has a considerably longer duration of action than the most commonly prescribed diuretic hydrochlorothiazide. Safety and tolerability between these two drugs are similar except higher serum uric acid and lower potassium levels with chlorthalidone. The combination of azilsartan medoxomil with chlorthalidone has been shown to be effective in lowering blood pressure with an acceptable safety and tolerability profile. This fixeddose combination is an attractive treatment option for hypertension management.

Compound danshen dripping pills affect the pharmacokinetics of azisartan by regulating the expression of cytochrome P450 2B1, 2C6, and 2C11 in rats

Combination therapies of compound danshen dripping pill (CDDP) and Azilsartan (AZ) represent a promising treatment option in clinical practice in China, but there are no reports on drug-drug interactions between CDDP and AZ. This study investigated the effects of CDDP on the pharmacokinetics of AZ and clarified its potential mechanism. The pharmacokinetic profiles of oral administration of AZ (2 mg/kg) in Sprague-Dawley rats, with or without pre-treatment of CDDP (81, 405, 810 mg/kg/d for 7 d) were investigated using UPLC-MS/MS. The main pharmacokinetic parameters were calculated and compared. The MS analysis was performed in positive ionization mode. The purpose of chromatographic separation of AZ and the internal standard (IS, Valsartan) was finished on a Waters XBridge BEH C18 column (2.1 × 100 mm, 2.5 μm). The mobile phase was acetonitrile and 0.1 % formic acid-water with gradient elution at a flow rate of 0.4 mL/min. The mRNA and protein levels of CYP2B1, CYP2C6, and CYP2C11 in the rat liver were detected by qRT-PCR and western blot, respectively. The results indicated that low, medium and high doses of CDDP significantly increased the Cmax (6.47 ± 2.28, 6.51 ± 1.99, 7.04 ± 1.31 vs. 3.30 ± 1.87) of AZ, compared with that in the AZ single-drug group (p<0.05). The AUC0-t of AZ (47.77 ± 23.41, 50.69 ± 25.46, 54.50 ± 11.57 vs. 26.85 ± 16.79) tended to increase in combination with CDDP. The gene and protein expression levels of CYP2B1, CYP2C6, and CYP2C11 were significantly reduced in the rat liver by CDDP. CDDP may diminish the AZ metabolism in vivo by suppressing the expression of the CYP2B1, CYP2C6, and CYP2C11 enzymes. This observation suggested the occurrence of potential interactions between CDDP and AZ when clinically administered as combination therapy, which may require adjustment of the clinical dose of AZ.

Experience with Azilsartan and Azilsartan Combined with Chlorthalidone in a Preventive Cardiology Center. Fighting the Therapeutic Inertia with a Program Based on Evidence, Personalization, and Empowerment

In patients with hypertension (HT), cardiovascular risk reduction is directly proportional to the reduction in blood pressure sustained over time. However, in “real life,” blood pressure control is often insufficient or not sustained over time to achieve optimal cardiovascular risk reduction. In this article, we comment on the multiple reasons which explain this common therapeutic failure. Also, in this article, we summarize the amazing basic and clinical phase III evidence of azilsartan (AZL) and azilsartan combined with chlortalidone (CLD), two excellent therapeutic options for HT control. With such evidence as scientific background, we communicate our results with almost 300 HT patients treated with azilsartan and azilsartan/chlortalidone in "real life." In brief, our findings were the following: a) In HT patients with blood pressure (BP) &lt;150/90 mmHg, AZL 40 mg as monotherapy provides practically 100% success to achieve a target BP &lt;140/90 and &lt;130/80 mmHg, in a subpopulation that we have called “hyper-responders” b) In HT patients with BP &lt;150/90 mmHg (naive or with another treatment failure), AZL/CLD 40/12.5 mg provides practically 100% success to achieve a target BP &lt;140/90 mmHg and 90% to achieve a target BP &lt;130/80 mmHg; c) In HT patients with BP &gt;150/90 mmHg (generally with another treatment failure), AZL/CLD 80/12.5 mg gives women a success rate greater than 60% to achieve a target BP &lt;140/90 mmHg and greater than 50% to achieve a target BP &lt;130/80 mmHg. The success rates were higher in men, greater than 75% to achieve a target BP &lt;140/90 mmHg and greater than 60% to achieve a target BP &lt;130/80 mmHg. In both cases, the use of amlodipine (2.5, 5, or 10 mg) made it possible to achieve a target BP &lt;140/90 mmHg in 100% of the cases and &lt;130/80 mmHg in 80% of the cases. Finally, according to our results, we propose a simple three-step strategy based on evidence, personalization, and empowerment which allows reaching a target BP &lt;140/90 mmHg in more than 90% of cases and a target BP &lt;130/80 mmHg in more than 75% of cases in 4 to 12 weeks.

An international multicenter observational non-interventional prospective study of the efficacy of azilsartan medoxomil in overweight or obese patients with arterial hypertension (CONSTANT)

Background 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. Methods 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. Results 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 (p < .001 compared to baseline value). A positive response to therapy was observed in 92.6% of cases (95% CI: 91.3–93.7%). Target blood pressure was achieved by 86.4% of cases (95% CI: 84.8–87.9%). During the study period 43 adverse events were recorded, the most common of which were arterial hypotension and dizziness. Conclusions 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.

Simultaneous estimation of azilsartan medoxomil and chlorthalidone by chromatography method using design of experiment and quality risk management based quality by design approach

Simultaneous estimation of azilsartan medoxomil and chlorthalidone by chromatography method using design of experiment and quality risk management based quality by design approach

A gadolinium-based magnetic ionic liquid for dispersive liquid-liquid microextraction.

A hydrophobic gadolinium-based magnetic ionic liquid (MIL) was investigated for the first time as an extraction solvent in dispersive liquid–liquid microextraction (DLLME). The tested MIL was composed of trihexyl(tetradecyl)phosphonium cations and paramagnetic gadolinium chloride anions. The prepared MIL showed low water miscibility, reasonable viscosity, markedly high magnetic susceptibility, adequate chemical stability, low UV background, and compatibility with reversed-phase HPLC solvents. These features resulted in a more efficient extraction than the corresponding iron or manganese analogues. Accordingly, the overall method sensitivity and reproducibility were improved, and the analysis time was reduced. The applicability of the proposed MIL was examined through the microextraction of four sartan antihypertensive drugs from aqueous samples followed by reversed-phase HPLC with UV detection at 240 nm. The DLLME procedures were optimized for disperser solvent type, MIL mass, disperser solvent volume, as well as acid, base, and salt addition. The limits of quantitation (LOQs) obtained with the analysis of 1.2-mL samples after DLLME and HPLC were 80, 30, 40, and 160 ng/mL for azilsartan medoxomil, irbesartan, telmisartan, and valsartan, respectively. Correlation coefficients were greater than 0.9988 and RSD values were in the range of 2.48–4.07%. Under the optimized microextraction conditions and using a 5-mL sample volume, enrichment factors were raised from about 40 for all sartans using a 1.2-mL sample to 175, 176, 169, and 103 for azilsartan medoxomil, irbesartan, valsartan, and telmisartan, respectively. The relative extraction recoveries for the studied sartans in river water varied from 82.5 to 101.48% at a spiked concentration of 0.5 μg/mL for telmisartan and irbesartan and 1 μg/mL for azilsartan medoxomil and valsartan. Graphical abstract Electronic supplementary materialThe online version of this article (10.1007/s00216-020-02992-z) contains supplementary material, which is available to authorized users.

Real-world effectiveness of treatments for type 2 diabetes, hypercholesterolemia, and hypertension in Canadian routine care – Results from the CardioVascular and metabolic treatment in Canada: Assessment of REal-life therapeutic value (CV-CARE) registry, 12-months results

AimsThe CV-CARE registry provides RWE in Canadian routine clinical practice. MethodsCV-CARE is a multi-site, observational, prospective Canadian registry enrolling patients initiating treatment with metformin hydrochloride extended-release (MetER) for T2D; colesevelam (C) for HCh; and azilsartan (AZI), azilsartan/chlorthalidone (AZI/CHL) or diltiazem extended-release (TXC) for HTN. Patient characteristics/assessment were performed at baseline and 12 ± 6 months. Primary outcome was absolute change in HbA1c and FPG (MetER); % change in LDL-C (C); and absolute change in BP (AZI-AZI/CHL-TXC). ResultsOf the 4194 patients in the primary analysis population, 24% were taking MetER, 39% were taking C, 33% were taking AZI, 12% were taking AZI/CHL, and 3% were taking TXC. At 12 months, MetER-treated patients had an absolute mean (95% CI) change in HbA1c of −0.3% [−0.4; −0.2] and in FPG of 0.7 mmol/L [−1.0; −0.4]. C-treated patients had a mean (95% CI) % change in LDL-C of −13.0% [−14.6; −11.4]. Absolute mean (95% CI) changes in SBP were −18.7 mmHg [−19.7; −17.7](AZI), −21.3 mmHg [−23.1; −19.5](AZI/CHL), and -12.3 mmHg [−15.1; −9.6](TXC). ConclusionIn a real-world Canadian setting, MetER, C, AZI, AZI/CHL, and TXC show improvement of the cardiometabolic profile of T2D, HCh, and HTN patients.

A phase 3 double-blind randomized (CONSORT-compliant) study of azilsartan medoxomil compared to valsartan in Chinese patients with essential hypertension: Erratum.

A phase 3 double-blind randomized (CONSORT-compliant) study of azilsartan medoxomil compared to valsartan in Chinese patients with essential hypertension: Erratum.

Synthesis of Two Novel Azilsartan Cocrystals: Preparation, Physicochemical Characterization and Solubility Studies

Azilsartan is a novel angiotension II receptor blocker primarily used to treat high blood pressure. This is not a formulation-friendly molecule largely due to the inherent water-solubility pitfalls. In this paper, two novel cocrystals of azilsartan (AZ) were studied (AZ-BIP, AZ-BPE; BIP = 4,4′-bipyridine, BPE = trans-1,2-bis (4-pyridyl) ethylene) by solution crystallization. The structures of these two cocrystals were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), including the single-crystal structure determination of AZ-BIP and AZ-BPE. In the cocrystals AZ-BIP (2:1) and AZ-BPE (2:1), two AZ molecules and one coformer formed a sandwich structure through N-H…N interactions. These sandwich structures were extended into a one-dimensional structure through O-H…N hydrogen bonds. The equilibrium solubility study demonstrated that the AZ-BIP and AZ-BPE cocrystals both showed higher solubility than azilsartan in water.

Azilsartan medoxomil for improving insulin resistance and adipokine levels in hypertension in comparison with angiotensin-converting enzyme inhibitors

Aim. To assess azilsartan medoxomil (AZM) in achieving the target blood pressure (BP) (<140/90 mm Hg), its angioprotective action in patients with hypertension (HTN), as well as contribution in reducing levels of adipokines and inflammation markers in patients switching from lisinopril or enalapril. Material and methods. This open-label observational study lasting 24 weeks included 60 patients who had previously received monotherapy with lisinopril 20 mg/day or enalapril 20 mg/day, and did not reach the target BP levels (<140/90 mm Hg). During the study, all patients underwent 24-hour BP monitoring, applanation tonometry (determination of the augmentation index and central BP), pulse wave velocity measurement, laboratory tests (lipid profile, uric acid, fasting glucose, HOMA index, homocysteine, leptin, adiponectin, highly sensitive C-reactive protein (hs-CRP), tumor necrosis factor alpha, interleukin-6 (IL-6). Results. After switching from lisinopril and enalapril to AZM, a decrease in systolic BP was 24,3% and 31,3%, diastolic BP — 19,8% and 21,4% (p<0,05). In the groups of initial therapy with lisinopril and enalapril, there was a decrease in central (aortic) BP by 20,4% and 25,5%, central pulse pressure by 20,6% and 27,6%, augmentation index by 33,1% and 34,58%, pulse wave velocity by 19,4% and 20,7% (p<0,05), levels of leptin by 10,4%, and 16,8%, hs-CRP by 16,1% and 19,3%, IL-6 by 23,6% and 25,1%, respectively. We also revealed an increase in adiponectin levels by 7,2% and 9,2%, respectively (p<0,05). Conclusion. Azilsartan medoxomil has advantages over angiotensin-converting enzyme inhibitors (enalapril, lisinopril) in achieving BP control, and improving vascular elasticity. It contributes to a decrease in insulin resistance and noninfectious inflammation.

2139-PUB: Antihypertensive Effect of Azilsartan in Newly Diagnosed Stage 2 Diabetic Hypertensives

Background and Aim: Coexistence of hypertension (HTN) and type 2 diabetes (T2DM) multiplies the risk of cardiovascular events. Early identification and prompt management of elevated blood pressure in T2DM has shown to improve the quality of life and to reduce the economic burden to the patients. We studied blood pressure (BP) lowering effect of Azilsartan (AZST) monotherapy in newly diagnosed stage 2 hypertensives with a history of T2DM. We also analysed its effects on blood glucose and renal indices. Methods: T2DM Subjects attending a specialized diabetes clinic, who were diagnosed with HTN for the first time, were invited to participate. Mean of 3 BP readings was considered for analysis after due consent. Subjects with stage 2 hypertension were administered AZST 40mg once daily. After 3 months they had a repeat BP recording. Subjects underwent serum creatinine, Na+, K+, fasting (FPG) and postprandrial (PPG) plasma glucose measurements at baseline and after 3moths’ of enrolment. We compared BP lowering efficacy and changes in plasma glucose and renal parameters at baseline and after 3months of AZST therapy. Diabetic, dyslipidemic and other chronic medicines were continued unchanged during the study period. Results: Inclusion criteria were met by 474 subjects (117, 25% females). Mean age and duration of diabetes were 53.3 (95% CI 52.3-54.3) and 7.03 (CI 6.6-7.5) years respectively. With AZST therapy mean SBP dropped from 152.7 (CI 151.1-154.3) mm Hg to 136.4 (CI 134.9-138.0) mm Hg (p &amp;lt;0.05) and the post treatment DBP declined to 79.6 (CI 78.8-80.4) mm Hg from its baseline value of 90.5 (CI 89.6-91.4) mm Hg (p &amp;lt;0.05). The mean baseline FPG and PPG were 158.8 (CI 154.0-163.4) mg/dL and 237.3 (CI 231.9-242.7) mg/dL in order. There was a non-significant decline in plasma glucose, but no changes were seen in eGFR or electrolytes. No adverse event was reported. Conclusion: Azilsartan monotherapy was found to be safe and effective in managing newly diagnosed stage 2 hypertension in type 2 diabetes without hampering renal function. Disclosure H. Mahapatra: None. M. Khuntia: None. S. Mishra: None. S.K. Mishra: None. R.K. Padhi: None. B. Jena: None. S. Das: None. R.K. Khatua: None. A.R. Jena: None. R. Mahapatra: None. L. Mahapatra: None. A.K. Sahoo: None. Funding Jyoti Diabetes Research Foundation

Regional variability in Canadian routine care of type 2 diabetes, hypercholesterolemia, and hypertension: Results from the The Cardio-Vascular and metabolic treatments in Canada: Assessment of REal-life therapeutic value (CV-CARE) registry

BackgroundRegional differences in the profile and treatment strategies of patients with cardiometabolic diseases have been studied in several different countries. The Cardio-Vascular and metabolic treatments in Canada: Assessment of REal-life therapeutic value (CV-CARE) registry was designed to evaluate patient profiles and medical management of cardiometabolic diseases in routine clinical care settings across Canada. Primary objectives were to (1) evaluate regional variability of patient profiles with cardiometabolic disease(s) and (2) assess treatment differences of patients treated for type 2 diabetes (T2D), hypercholesterolemia (HCh), and hypertension (HTN) across Canada. MethodsCV-CARE is a multi-center, observational, prospective registry that enrolled Canadian patients treated with metformin-extended release (MetER) for T2D, colesevelam (C) for HCh, azilsartan (AZI) for mild-to-moderate essential HTN and azilsartan/chlorthalidone (AZI/CHL) for severe, essential HTN. Patient characteristics and treatments were assessed at baseline. ResultsThe registry enrolled 6960 patients, with a total of 4194 patients making up the primary analysis population [MetER (n=995); C (n=1639); AZI (n=1364); AZI/CHL (n=498)]. First-line use of MetER was more common in British Columbia (BC; 45.5%) compared to Ontario (ON; 29.8%), and Quebec (QC; 12.9%). C treatment for HCh was used as monotherapy most readily in BC (68.7%) compared with QC (59.7%) and ON (35.8%). Dual action of low-density lipoprotein cholesterol and hemoglobin A1c reduction was the predominant reason for C add-on therapy (46.8%), with highest usage seen in ON (62.9%). AZI treatment for HTN was most frequently used in BC (43.8%), and AZI/CHL was most commonly used in ON (12.0%). First-line use of AZI was more common in QC (50%) vs. ON (34.9%) and BC (24.1%). The primary reason for switching to AZI and AZI/CHL from prior treatment was lack of efficacy across provinces. ConclusionThis is the first regional description of the CV-CARE cohort. Significant variations in both baseline profile and treatments were observed which could have an impact on long-term outcomes.

Development and Validation of Stability Indicating Chromatographic Methods for Determination of Azilsartan Medoxomil in Pharmaceutical Formation

Two stability-indicating chromatographic methods namely, reverse-phase high-performance liquid chromatography (RP-HPLC) and high-performance thin-layer chromatography (HPTLC) were developed and validated for the determination of azilsartan medoxomil from pharmaceutical dosage form in presence of its degradation products as per ICH guideline. In RP-HPLC, separation was performed with Hiber® C-18 column (250 mm X 4.6 mm, 5 μm), using mobile phase methanol: acetonitrile: water (88:8:4 v/v/v) at a flow rate of 0.5 ml/min. The analyte was detected at 254 nm over a concentration range of 20 - 70 μg/ml with correlation coefficient of 0.999. In HPTLC, separation was carried out with silica gel G60 F254 aluminum sheet using acetone: toluene: ammonia (8.2:1.7:0.1 v/v/v) as a developing system. Linearity of the proposed HPTLC method was found 500 - 900 ng/band and correlation coefficient 0.9970 at 254 nm. Besides, stress degradation study was also carried out wherein degraded product peaks were well resolved from the analyte peak with difference in their retention time and retardation factor in RP-HPLC and HPTLC methods respectively. Statistical analysis proved that there were no significant differences between the two validated methods. The proposed stability-indicating methods can be applied for the analysis of azilsartan medoxomil in pharmaceutical formulations for quality control.

The Comparative Study of Azilsartan with Telmisartan in Terms of Efficacy, Safety and Cost - Effectiveness in Hypertension

Introduction: Hypertension (HT) represents the most common cardiovascular risk factor amongst the cluster group of Cardiovascular Diseases (CVD). Clinically, HT might be defined as that level of Blood Pressure (BP) at which the institution of therapy reduces the BP-related morbidity and mortality. Azilsartan (AZL) is a relatively new Angiotensin Receptor Blocker (ARB) available for the treatment of any stage of HT. Aim: To compare the efficacy, safety and cost-effectiveness of AZL 40-80 mg once daily versus telmisartan 40-80 mg once daily in patients of stage-I HT. Methods: A prospective, open, randomized parallel group comparative study of AZL versus telmisartan was done in patients of stage-I HT. The study included 80 patients, 40 in each group (group I and group II) coming to the department of Medicine, Rajindra Hospital attached to Government Medical College, Patiala. The study was conducted over 8 weeks. Group I, patients received Azilsartan 40-80 mg per day in divided doses and group II, patients received telmisartan 40-80 mg per day in divided doses according to severity of hypertension. The therapeutic efficacy of drugs was evaluated by monitoring BP. Adverse drug reactions were monitored in patients. The daily cost for each medication was noted and total cost of drugs taken over 8 weeks was calculated. Effectiveness of the drugs was calculated in terms of mm Hg fall in mean BP. All the observations thus made were statistically analyzed using appropriate tests. Results: Patients receiving AZL 40mg and telmisartan 40mg showed a significant fall (p<0.05) in systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at 4 weeks and 8 weeks, when compared to baseline. The difference in SBP and DBP between Group I (AZL) and II (Telmisartan) was statistically significant at 4 weeks (p<0.05) and was highly significant at 8 weeks (p<0.001). Adverse effects such as nasopharyngitis, upper respiratory tract infection, gastroenteritis, headache, dizziness, and fatigue were reported with both drugs. Conclusions: Reduction of BP with AZL was more as compared to telmisartan at 4 weeks and 8 weeks. Safety and tolerability was similar in both groups.