Olmesartan Group Research Articles

P4482Antihypertensive drugs in experimental NAFLD as the first step to the establishment of criteria for choosing appropriate treatment of hypertension in NAFLD carriers

Abstract Background/Introduction Hypertension is highly prevalent in NAFLD patients (39%). NAFLD has been independently associated with an increased risk of arterial hypertension in observational studies and emerge as the most frequent cause of chronic hepatic disease in adults. Therefore, we can deduce that treating hypertension in NAFLD carriers will be often necessary. However, there are no established criteria for choosing the most appropriate drug therapy for hypertension in patients with NAFLD, and the basic research may be the first step to the development of these criteria. Purpose We aimed to evaluate the effects of the renin-angiotensin system blockade with angiotensin-converting enzyme inhibitor ramipril and angiotensin 2 type 1 receptor antagonist olmesartan, used preventively, in NAFLD induced in rabbits fed hypercholesterolemic diet. Antihypertensive drugs in experimental NAFLD as the first step to the establishment of criteria for choosing appropriate treatment of hypertension in NAFLD carriers. Methods Olmesartan study: Thirty-four rabbits were divided into three groups (control, untreated and olmesartan). The untreated and olmesartan group were fed a hypercholesterolemic diet. Animals from olmesartan group were treated with olmesartan 1mg/kg/day. Ramipril study: Twenty-nine rabbits were divided into three groups (normal, placebo, and ramipril). The placebo and ramipril groups were fed a hypercholesterolemic diet. The groups were orally administered 0.35 mg/kg/day of ramipril, and an equivalent volume of vehicle was administered to the placebo group. In both studies, at the end of the 8th week, all rabbits underwent segmental hepatic resection and were euthanised. Blood samples were collected to determine glucose, creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and aminotransferase levels at baseline and euthanasia. Haematoxylin and eosin and Gomori trichrome stained slides were analysed based on the histological scoring system for NAFLD. Results The comparison between two groups (olmesartan with untreated group and ramipril with placebo) showed that ramipril and olmesartan significantly diminished the development of steatosis (p<0.013, p=0.032), lobular inflammation (p<0.001, p=0.006), and fibrosis (p=0.015, p=0.02). Based on NAFLD activity score, olmesartan and ramipril significantly reduced the development of nonalcoholic steatohepatitis (p<0.001, p=0.003). Conclusion(s) The preventive use of olmesartan and ramipril attenuates the development of hepatic steatosis, lobular inflammation and fibrosis in hypercholesterolemic rabbits. These results can serve as the basis to the establishment of criteria for choosing the most appropriate drug therapy for hypertension in NAFLD carriers.

BLOOD PRESSURE LOWERING EFFICACY OF TELMISARTAN, AZILSARTAN, OLMESARTAN TAKING ON THE MORNING OR AT BEDTIME IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

Objective: Aim study was compared the antihypertensive effects of morning (a.m.) and evening (p.m.) dosing of olmesartan, azilsartan, telmisartan on 24-h BP. Design and method: 126 patients (57 men, 69 women) was included in 12-week study with evaluated the efficacy and safety of olmesartan 20–40 mg (n = 40), azilsartan 40–80 mg (n = 41), telmisartan 40–80 mg (n = 45), dosed a.m. or p.m., in patients with grade 1–2 hypertension. Mean ages 51,80 ± 1,31, BMI - 28,81 ± 0,39 kg/m2. Mean 24SBP – (135,60 ± 0,96) mmHg., 24DBP – (82,41 ± 0,84) mmHg., 24HR – (71,88 ± 0,89) b.p.m. Results: Mean 24-h SBP/DBP change from baseline to Weeks 12 in olmesartan group was benefit (−11,09 ± 2,30/8,38 ± 2,58 mmHg) in p.m. compared (−4,06 ± 2,25/3,38 ± 2,31mmHg) in a.m., p < 0,01 between evening and morning administration. Mean 24-h SBP/DBP change in azilsartan group was comparable in p.m. (−13,06 ± 2,65/9,76 ± 1,73 mmHg) and a.m. (−12,71 ± 1,62/7,00 ± 1,50 mmHg) in a.m., p > 0,05 between evening and morning. Mean 24-h SBP/DBP change from baseline to Weeks 12 in telmisartan group was benefit (−16,48 ± 2,86/12,56 ± 2,80 mmHg) in a.m. compared (−4,93 ± 1,53/5,40 ± 1,89 mmHg) in p.m., p < 0,01 between morning and evening administration. All treatments were well tolerated. At 24-h BP, with the administration of olmesartan, azilsartan and telmisartan, the target blood pressure levels were 71.80%, 71.05% and 75.61% respectively. Thus, all three drugs have equally effectively. Conclusions: Taking telmisartan more significantly reduced the 24-h BP in the morning compared with the evening adminisrtation, olmesartan lowered 24-h BP better in the evening administration, and the use of azilsartan equally decreased 24-h BP, regardless of the time of taking the drug.

Severe intestinal malabsorption associated with ACE inhibitor or angiotensin receptor blocker treatment. An observational cohort study in Germany and Italy.

PurposeThe angiotensin II receptor blocker (ARB) olmesartan has been recently associated with sprue‐like enteropathy (SLE), a gastrointestinal condition characterized by intestinal malabsorption (IM) and severe diarrhea. Whether the increased risk of SLE is substance‐specific or a class effect involving all ARBs is uncertain. The aim of this study is to assess the risk of enteropathy associated with ARBs and angiotensin converting enzyme inhibitors (ACE‐i) by using data from large administrative and claim databases.MethodsWe obtained data from Italian local health‐care units and a large German claim database and included patients treated with olmesartan, other ARBs, and ACE‐i. In the absence of a specific diagnosis code for SLE, International Classification of Diseases codes for IM were used. Analysis implemented a Poisson regression with robust error variance procedure, which allowed accounting for different clusters (local health‐care units and countries) and correctly estimating the standard error for the relative risk of rare event occurrence.ResultsPatients were divided into 3 groups: olmesartan (25.591, 5.5%), other ARBs (104.901, 22.5%), and ACE‐i patients (334.951, 72.0%). Baseline characteristics were similar overall. The incidence of unspecified IM in ACE‐i patients was not different compared with that of olmesartan, whereas a higher rate ratio was observed when comparing ARB patients with the olmesartan group (RR: 2.50, 95% CI 1.21 to 5.19, P .01). When International Classification of Diseases codes for coeliac disease were included, no differences were observed.ConclusionsWe could not confirm previous findings of a higher risk of malabsorption in olmesartan‐only patients, and drug‐induced enteropathy should be considered the result of exposure to the class of ARBs rather than a specific drug‐related effect.

Efficacy and safety of sacubitril/valsartan in patients with essential hypertension uncontrolled by olmesartan: A randomized, double-blind, 8-week study.

A majority of patients with hypertension fail to achieve blood pressure (BP) control despite treatment with commonly prescribed drugs. This randomized, double-blind phase III trial assessed the superiority of sacubitril/valsartan 200mg (97/103mg) to continued olmesartan 20mg in reducing ambulatory systolic BP after 8-week treatment in patients with mild to moderate essential hypertension uncontrolled with olmesartan 20mg alone. A total of 376 patients were randomized to receive either sacubitril/valsartan (n=188) or olmesartan (n=188). Superior reductions in 24-hour mean ambulatory systolic BP were observed in the sacubitril/valsartan group vs the olmesartan group (-4.3mmHg vs -1.1mmHg, P<.001). Reductions in 24-hour mean ambulatory diastolic BP and pulse pressure and office systolic BP and diastolic BP were significantly greater with sacubitril/valsartan vs olmesartan (P<.014). A greater proportion of patients achieved BP control with sacubitril/valsartan vs olmesartan. The overall incidence of adverse events was comparable between the groups. Compared with continued olmesartan, sacubitril/valsartan was more effective and generally safe in patients with hypertension uncontrolled with olmesartan 20mg.

Predictors for the development of microalbuminuria and interaction with renal function.

It is important to know which factors predict the development of microalbuminuria in patients with diabetes mellitus type II. Data from the Randomized Olmesartan and Diabetes Microalbuminuria Prevention Study were used to identify predictors for the new onset of microalbuminuria. Furthermore, the interaction of baseline albuminuria and baseline estimated glomerular filtration rate (eGFR) and the effects of treatment with olmesartan were investigated. A total of 4447 patients were randomized to receive 40-mg olmesartan or placebo for a median of 3.2 years. Baseline urinary albumin-creatinine ratio (UACR) was the most important predictor of microalbuminuria, followed by age, weight, glycosylated hemoglobin type A1C, blood glucose, total cholesterol, SBP number of antihypertensive drugs and heart rate. The development of microalbuminuria was not affected by hemodynamic factors. The incidence of microalbuminuria increased from the lower to the higher UACR tertile at all baseline eGFR tertiles. The effects of olmesartan on prevention of new onset microalbuminuria were more obvious in those with the highest baseline UACR at all baseline eGFR tertiles. The eGFR declined more significantly in the olmesartan group (from 85.0 to 80.1 ml/min per 1.73 m), whereas the decrease in the placebo group was smaller (from 84.7 to 83.7 ml/min per 1.73 m). The highest rate of eGFR decline in the olmesartan group was in patients with the highest baseline eGFR (>95 ml/min per 1.73 m) at all baseline UACR tertiles. The transition from normoalbuminuria to microalbuminuria in the olmesartan treated patients was not accompanied by preservation of renal function. Predictors of new onset microalbuminuria are the classical cardiovascular risk factors. Microalbuminuria development was associated with baseline UACR but not baseline eGFR, whereas eGFR decrease after introduction of olmesartan was dependent on baseline eGFR but not on baseline UACR. The effects of olmesartan on microalbuminuria development and on eGFR decrease are probably mediated by different mechanisms.Clinical Trials.gov number, NCT00185159.

Efficacy and Safety of Sacubitril/Valsartan (LCZ696) Compared With Olmesartan in Elderly Asian Patients (≥65 Years) With Systolic Hypertension.

Systolic hypertension is common in elderly patients and remains a challenge to treat effectively. The efficacy and safety of sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, vs. olmesartan was evaluated in elderly Asian patients (≥65 years) with systolic hypertension. In this randomized, double-blind, 14-week study, patients initially received once-daily sacubitril/valsartan 100 mg or olmesartan 10 mg, increased to sacubitril/valsartan 200 mg or olmesartan 20 mg at week 4. At week 10, for patients with blood pressure (BP) >140/90 mm Hg, the doses were up-titrated to sacubitril/valsartan 400 mg or olmesartan 40 mg. The primary assessment was superiority of sacubitril/valsartan vs. olmesartan in reducing office mean sitting (ms) systolic BP (msSBP) from baseline at week 10. Secondary efficacy assessments included changes from baseline in ms diastolic BP (msDBP), ms pulse pressure (msPP), 24-hour mean ambulatory (ma) BP (maBP), and maPP at week 10; msBP and msPP at weeks 4 and 14. Overall, 588 patients were randomized (mean age, 70.7 years; baseline msBP, 160.3/84.9 mm Hg; msPP, 75.4 mm Hg). At week 10, sacubitril/valsartan provided superior msSBP reductions vs. olmesartan (22.71 vs. 16.11 mm Hg, respectively; P < 0.001); similarly, reductions from baseline in other BP and PP assessments were significantly greater with sacubitril/valsartan. At week 14, despite more patients requiring up-titration in the olmesartan group, msBP and msPP reductions from baseline were significantly greater with sacubitril/valsartan. Both treatments were generally well-tolerated. Sacubitril/valsartan is more effective than olmesartan in reducing BP in elderly Asian patients with systolic hypertension.

ADMA, SDMA and L-arginine may be Novel Targets in Pharmacotherapy for Complications due to Cardiopulmonary Bypass.

SummaryBackgroundIn this study, the effects of olmesartan therapy on asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-arginine and inducible nitric oxide synthase (iNOS) levels were investigated in patients undergoing cardiopulmonary bypass.MethodsPatients were randomly allocated to two groups, control and olmesartan. Olmesartan was administered 30 mg once a day beginning from preoperative day 5 to postoperative day 28 and on operation day. Blood was drawn from all patients and ADMA, SDMA, L-arginine and iNOS levels were analyzed at six time points (T1: before anesthesia induction, T2: during cardiopulmonary bypass, T3: five min after the cross-clamp was removed, T4: after protamine infusion, T5: on postoperative day 3 and T6: on postoperative day 28).ResultsIn the olmesartan treated group, iNOS levels exhibited significant decreases at T2, T3, T4, T5 and T6 time points compared with control group (p<0.001, p<0.05, p<0.001, p<0.01, p<0.05 respectively). ADMA levels were significantly lower in olmesartan treated group than in control group at T3, T4, T5 and T6 time points (p<0.05, p<0.05, p<0.05, p<0.01 respectively). SDMA levels at T2, T3 and T6 time points were higher in control group than olmesartan group. L-Arginine levels were significantly higher at T2 and T3 time points in olmesartan treated group than control group (p<0.001, p<0.01).ConclusionsIt was concluded that administration of olmesartan reduced plasma ADMA, SDMA, iNOS levels and enhanced L-arginine level in CPB time and it could reduce potential postoperative complications through reducing oxidative stress and inflammatory response in the postoperative period after coronary bypass surgery.

Comparison of Efficacy and Safety of Azilsartan and Olmesartan in Patients With Essential Hypertension.

Many patients still have high blood pressure (BP) after treatment with angiotensin II type 1 (AT1) receptor blockers (ARBs). We compared the efficacy and safety of azilsartan to those of olmesartan in a prospective randomized clinical trial. Sixty-four hypertensive patients who were treated with ARBs other than azilsartan and olmesartan were enrolled in this study. We randomly assigned patients to changeover from their prior ARBs to either azilsartan or olmesartan, and followed the patients for 3 months. Systolic BP (SBP) in the azilsartan group was significantly decreased at 3 months, and diastolic BP (DBP) and pulse rate (PR) in the olmesartan group showed significant reductions after 3 months. There were no significant differences in ΔSBP, ΔDBP, or ΔPR (Δ = the value at 3 months minus the value at 0 months) between the groups. Serum levels of creatinine (Cr), uric acid (UA), and potassium (K) in the azilsartan group significantly increased after 3 months. While the changes in Cr, UA, and K were within the respective normal ranges, ΔSBP was positively associated with ΔCr in the azilsartan group. In conclusion, there was no difference in the depressor effects of azilsartan and olmesartan, and there were no serious changes in biochemical parameters with azilsartan and olmesartan.

Angiotensin II Receptor Blockers or Straight Renin Inhibitor Influence Upon Morphological and Functional Heart and Central Hemodynamics Indices in Hypertensive Patients After Ischemic Stroke

Arterial hypertension (AH) in the world and in Ukraine is the main cause of strokes and chronic cerebral dyscirculation with constantly growing incidence. The risk of recurrent stroke grows with increase of concomitant risk factors and AH target organs damage. Asymptomatic target organs damage, especially, LV hypertrophy, etc., is one the potent factors for cerebral vascular complications in hypertensive patients. That is why treatment of heart anatomy alterations, as a target organ, is of great importance in cardiovascular continuum for primary and secondary prevention of cardiovascular, including cerebrovascular end-points. The objective: of the study was to evaluate the influence of AH medication treatment by angiotensin receptors type II blockers (ARB) and straight renin inhibitor upon morphological and functional heart indices and central hemodynamics in hypertensive patients after ischemic stroke (IS) during 1 year follow-up according to stroke and vascular hospital departments experience. Patients and methods. We prospectively included 135 hypertensive pts. without AF history after IS aged 36-78 years (61,0±9,1 yrs.), hospitalized to stroke and vascular hospital departments of Ternopol regional community psycho-neurological hospital (TRCPNH) over the period Nov. 2011 – Dec. 2013 р. All pts. underwent Doppler EchoCG. Along with fundamental therapy pts. were randomly prescribed Losartan 50-100 mg/day (40 pts.), Olmesartan 20-40 mg/day (48 pts) or Aliskiren 150-300 mg/day. Control EchoCG was performed in 6 and 12 months from trearment start. Results. Among the pts. with AH after IS usually there are pts. with low NYHA class of CHF, with LVEF correlating with NYHA functional class ( –0,47, p&lt;0,0001), with predominantly concentric LV geometry (97,8%), correlating with NYHA functional class. NYHA FC significantly correlates with most morphological and functional left and right remodeling indices, while LV volumes significantly correlate with LV systolic function. ARB administration (Losartan or Olmesartan) for AH treatment leads to marked significant regress of LV hypertrophy and hypertensive remodeling already in 6 months of treatment with central hemodynamics improvement with similar changes in both sartans groups without significant difference between indices. In Aliskiren group (3) in 6 months of treatment pts. Showed significantly higher LA dimensions compared to Losartan group, thicker LV walls compared to both sartan groups, and higher LV RWTh. Central hemodynamics indices, namely, LV diastolic function, LV preload and smaller circulation pressure in 6 months after treatment did not significantly differ between the groups. Conclusions. In Aliskiren group in 12 months of treatment there also were certain positive changes compared to start data, witnessing of reverse LV remodeling. But at the same time Aliskiren group showe significantly higher LV walls thickness (р=0,0051 and р&lt;0,0001 for IVS, and р&lt;0,0001 and р&lt;0,0001 fro LVPW, respectively), and higher LV MMi (р=0,0003 and р=0,0002, respectively) compared both to Losartan and Olmesartan groups, with preservation of concentric LV geometry and LV hypertrophy. Also, Aliskiren group showed significantly worse LV diastolic function and preload indices, allowing to conclude about insufficient cardioprotection with Aliskiren in treating AH after IS, and significant benefit from ARB.

Olmesartan Reduces New-onset Atrial Fibrillation and Atrial Fibrillation Burden after Dual-chamber Pacemaker Implantation in Atrioventricular Block Patients.

Background:Atrial fibrillation (AF) is the most frequent tachyarrhythmia in patients with a permanent pacemaker. Angiotensin II receptor antagonists have a protective effect against the occurrence of AF in patients with heart diseases. This study aimed to assess the effectiveness of olmesartan in the prevention of new-onset AF and AF burden in atrioventricular block (AVB) patients with dual-chamber (DDD) pacemaker implantation.Methods:This was a single-center, prospective, randomized, single-blind, controlled clinical study. A total of 116 AVB patients, who received DDD pacemakers implantation with the percentage of ventricular pacing (VP%) ≥40% from April 22, 2011 to December 24, 2012, were prospectively randomized to olmesartan group (20 mg per day; n = 57) or control group (n = 59). Patients were followed up using pacemaker programming, 12-lead electrocardiography in the intrinsic sinus rhythm, laboratory examinations, and transthoracic echocardiography at 24 months. Atrial high rate events (AHREs) were defined as 180 beats/min over a minimum of 5 min. AF burden was calculated by the number of hours with AHREs divided by the number of measurement hours.Results:Ten (17.5%) patients in the olmesartan group and 24 patients (40.7%) in the control group occurred new-onset AF, and the difference between two groups was statistically significant (P = 0.04). AF burden was lower in olmesartan group than that in control group (8.02 ± 3.10% vs. 13.66 ± 6.14%, P = 0.04). There were no significant differences in mean days to the first occurrence of AHREs and mean cumulative numbers of AHREs between two groups (P = 0.89 and P = 0.42, respectively). Moreover, olmesartan group had smaller values of maximal P-wave durations and P-wave dispersion (PD) after 24 months follow-up compared with the control group (109.5 ± 7.4 ms vs. 113.4 ± 7.1 ms, P = 0.00; and 40.6 ± 4.5 ms vs. 43.3 ± 4.4 ms, P = 0.02, respectively). Left ventricular end-diastolic diameter and left ventricular ejection fraction were not significantly different between two groups (both P > 0.05).Conclusion:This study suggested that 24-month of olmesartan therapy could reduce new-onset AF and AF burden in patients with DDD pacemakers.Clinical Trial Registration:ChiCTR-TRC-12004443; http://www.chictrdb.org.

Depressor and Anti-Inflammatory Effects of Angiotensin II Receptor Blockers in Metabolic and/or Hypertensive Patients With Coronary Artery Disease: A Randomized, Prospective Study (DIAMOND Study).

BackgroundWe compared the efficacy and safety of azilsartan to those of olmesartan in a prospective, randomized clinical trial.MethodsForty-four hypertensive patients who had coronary artery disease (CAD) were enrolled. We randomly assigned patients to changeover from their prior angiotensin II receptor blockers (ARBs) to either azilsartan or olmesartan, and followed the patients for 12 weeks.ResultsOffice systolic blood pressure (SBP) in the azilsartan group was significantly decreased after 12 weeks. SBP and diastolic blood pressure (DBP) after 12 weeks in the azilsartan group were significantly lower than those in the olmesartan group. The percentage of patients who reached the target BP at 12 weeks (78%) in the azilsartan group was significantly higher than that at 12 weeks (45%) in the olmesartan group. There were no significant changes in pentraxin-3, high-sensitively C-reactive protein or adiponectin in blood after 12 weeks in either group. Although serum levels of creatinine (Cr) in the azilsartan group significantly increased, these changes were within the respective normal range.ConclusionIn conclusion, the ability of azilsartan to reduce BP may be superior to that of prior ARBs with equivalent safety in hypertensive patients with CAD.

Olmesartan ameliorates pressure overload-induced cardiac remodeling through inhibition of TAK1/p38 signaling in mice

AimsMany studies have demonstrated the potent effects of ARB administration on heart failure. However, the mechanism of the potent effects of ARB on cardiac remodeling is less well understood. We investigated the role of Olmesartan on the fibrosis and hypertrophy in mouse heart. Materials and methodsWe employed TAC surgery, a mouse model of chronic cardiac failure. All the mice were separated into three groups: the sham group, TAC group and TAC plus Olmesartan group (given Olmesartan treatment after TAC). We analyzed left ventricle remodeling, and function by echocardiography or pathology. We further detected the level of marker genes involved in fibrosis and hypertrophy and in cultured neonatal rat cardiac fibroblasts and myocytes infected by constitutively active TAK1 and p38MAPK. After TAC, all the mice developed hypertrophy, worse cardiac function and malignant remodeling in left ventricle. Key findingsOlmesartan improved heart remodeling and function without changing pressure of blood. Moreover, Olmesartan reduced the level of transforming growth factor β activated kinase-1 (TAK1) and phospho-p38MAPK. In neonatal rat cardiac fibroblast cells and cardiomyocytes, Olmesartan also decreased TAK1 and p38MAPK activation triggered by TGFβ1 or AngII. The inhibitory effect of Olmesartan was abrogated by overexpression of constitutively active TAK1 and p38MAPK by adenovirus system. SignificanceOur results suggest Olmesartan improves heart remodeling and function induced by pressure overload. P38MAPK inactivation attenuated by olmesartan via inhibition of TAK1 pathway plays an important role in the process.

Severe intestinal malabsorption associated with olmesartan: a French nationwide observational cohort study.

Severe sprue-like enteropathy associated with olmesartan has been reported, but there has been no demonstration of an increased risk by epidemiological studies. To assess, in a nationwide patient cohort, the risk of hospitalisation for intestinal malabsorption associated with olmesartan compared with other angiotensin receptor blockers (ARB) and ACE inhibitors (ACEIs). From the French National Health Insurance claim database, all adult patients initiating ARB or ACEI between 1 January 2007 and 31 December 2012 with no prior hospitalisation for intestinal malabsorption, no serology testing for coeliac disease and no prescription for a gluten-free diet product were included. Incidence of hospitalisation with a discharge diagnosis of intestinal malabsorption was the primary endpoint. 4 546 680 patients (9 010 303 person-years) were included, and 218 events observed. Compared with ACEI, the adjusted rate ratio of hospitalisation with a discharge diagnosis of intestinal malabsorption was 2.49 (95% CI 1.73 to 3.57, p<0.0001) in olmesartan users. This adjusted rate ratio was 0.76 (95% CI 0.39 to 1.49, p=0.43) for treatment duration shorter than 1 year, 3.66 (95% CI 1.84 to 7.29, p<0.001) between 1 and 2 years and 10.65 (95% CI 5.05 to 22.46, p<0.0001) beyond 2 years of exposure. Median length of hospital stay for intestinal malabsorption was longer in the olmesartan group than in the other groups (p=0.02). Compared with ACEI, the adjusted rate ratio of hospitalisation for coeliac disease was 4.39 (95% CI 2.77 to 6.96, p<0.0001) in olmesartan users and increased with treatment duration. Olmesartan is associated with an increased risk of hospitalisation for intestinal malabsorption and coeliac disease.

Protective effect of angiotensin II receptor blocker and calcium channel blocker on endothelial vasomotor function after everolimus-eluting stent implantation

BackgroundEndothelial dysfunction after drug-eluting stent implantation has been demonstrated. It may be associated with adverse cardiovascular events during follow-up. Olmesartan, an angiotensin II receptor antagonist, ameliorates endothelial dysfunction. The present study evaluated the protective effect of olmesartan on endothelial function after everolimus-eluting stent (EES) implantation. MethodsA total of 40 patients who underwent EES implantation were randomly assigned to the olmesartan group (20 patients with 30 lesions) or the non-olmesartan group (20 patients with 32 lesions). Endothelial function was estimated by measuring the coronary vasoreactivity in the segments 15mm proximal and distal to EES in response to intracoronary infusion of acetylcholine (Ach; 10−8 and 10−7mol/L) at 9-month follow-up. Endothelium-independent vasomotion was assessed after an intracoronary bolus of isosorbide dinitrate. ResultsIn both groups, Ach infusion did not induce significant vasoconstriction in the segment either proximal or distal to the EES. The changes in coronary diameter in response to 10−8mol/L (−2.0±4.4% vs. −0.6±4.1%, p=0.33) and 10−7mol/L (−1.8±7.9% vs. −0.3±7.6%, p=0.57) Ach infusion in the segment proximal to EES were not significantly different between the olmesartan group and the non-olmesartan group. There were no significant differences in vasoconstriction in response to 10−8mol/L (−0.8±5.8% vs. −0.9±7.0%, p=0.96) and 10−7mol/L (1.8±9.7% vs. −1.8±9.7%, p=0.16) Ach infusion in the segment distal to EES between the 2 groups. Endothelium-independent vasodilation after nitrate infusion did not differ between the 2 groups. ConclusionsEndothelial dysfunction is not observed after EES implantation. Olmesartan does not improve endothelial function after EES implantation.

PP.07.18

Objective: Diuretics are first line drugs for the treatment of hypertension. Due to their low cost there are limited studies on their effect as a monotherapy on vascular properties. They are mostly used in combination therapy, and there is not much data on their effects as monotherapy compared to other drugs. We aimed to investigate the short term effect of chlorthalidone and olmesartan in arterial stiffness in patients with newly diagnosed essential hypertension. Design and method: We recruited 28 patients on the olmesartan group and 23 on the chlortalidone group matched for age, gender, and BMI. The patients were followed for three months. Dose of medication was titrated to achieve blood pressure (BP) goal. PWV was measured by Sphygmocor (Atcor Medical). Central systolic aortic BP (CSBP), Central diastolic BP (CDBP) was assessed by applanation tonometry, 24-hour SBP and 24-hour DBP were also measured (Spacelabs 90216), and clinic SBP and DBP were measured according to international guidelines. Results: All BP pressure parameters showed no difference at the end of the study with the exception of clinic DBP (δDBP = -11.2 ± 12.4 and -0.56 ± 19.9 mmHg for olmesartan and chlorthalidone, p < 0.05). PWV and AIx were comparable at the end of the study in the two groups (δPWV = -0.2 ± 1.8 vs -0.9 ± 2.7 m/sec for olmesartan and chlorthalidone, p > 0.05). Conclusions: 24-hour BP parameters and central BP parameters showed a similar reduction at the end of the study for the two drugs. Further, there was no class effect on arterial stiffness parameters between the diuretic and the angiotensin receptor blocker.

Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure: the supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial.

We examined whether an additive treatment with an angiotensin receptor blocker, olmesartan, reduces the mortality and morbidity in hypertensive patients with chronic heart failure (CHF) treated with angiotensin-converting enzyme (ACE) inhibitors, β-blockers, or both. In this prospective, randomized, open-label, blinded endpoint study, a total of 1147 hypertensive patients with symptomatic CHF (mean age 66 years, 75% male) were randomized to the addition of olmesartan (n = 578) to baseline therapy vs. control (n = 569). The primary endpoint was a composite of all-cause death, non-fatal acute myocardial infarction, non-fatal stroke, and hospitalization for worsening heart failure. During a median follow-up of 4.4 years, the primary endpoint occurred in 192 patients (33.2%) in the olmesartan group and in 166 patients (29.2%) in the control group [hazard ratio (HR) 1.18; 95% confidence interval (CI), 0.96–1.46, P = 0.112], while renal dysfunction developed more frequently in the olmesartan group (16.8 vs. 10.7%, HR 1.64; 95% CI 1.19–2.26, P = 0.003). Subgroup analysis revealed that addition of olmesartan to combination of ACE inhibitors and β-blockers was associated with increased incidence of the primary endpoint (38.1 vs. 28.2%, HR 1.47; 95% CI 1.11–1.95, P = 0.006), all-cause death (19.4 vs. 13.5%, HR 1.50; 95% CI 1.01–2.23, P = 0.046), and renal dysfunction (21.1 vs. 12.5%, HR 1.85; 95% CI 1.24–2.76, P = 0.003). Additive use of olmesartan did not improve clinical outcomes but worsened renal function in hypertensive CHF patients treated with evidence-based medications. Particularly, the triple combination therapy with olmesartan, ACE inhibitors and β-blockers was associated with increased adverse cardiac events. This study is registered at clinicaltrials.gov-NCT00417222.

In a methotrexate-induced model of intestinal mucositis, olmesartan reduced inflammation and induced enteropathy characterized by severe diarrhea, weight loss, and reduced sucrose activity.

The aim of this study was to evaluate the effect of olmesartan (OLME), an angiotensin II receptor antagonist, on an intestinal mucositis model. Briefly, daily intraperitoneal (i.p.) injections of methotrexate (MTX) 7 mg/kg were administered to rats on 3 consecutive days. A subset of these rats was also pretreated with oral administration of OLME (0.5, 1.0, or 5.0 mg/kg) or vehicle as a control 30 min prior to MTX injection. Body weight, feces scoring, and death were recorded daily. On day 4, the rats were killed, and intestinal tissues were assayed for levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, myeloperoxidase and sucrose activity, and histopathological findings. A significant reduction in body weight was observed in the MTX+1.0 mg/kg OLME group (p<0.01). The feces scores for the MTX+0.5 mg/kg OLME and MTX+5.0 mg/kg OLME groups were also significantly higher (p<0.001). Sucrose activity was reduced in all groups treated with OLME (p<0.05). Treatment with MTX+OLM at all doses resulted in reduced inflammatory infiltration, ulcerations, vasodilation, and hemorrhagic areas (p<0.05), as well as reduced concentrations of myeloperoxidase (p<0.001). The IL-1β and TNF-α levels were decreased in the MTX+OLME 5.0 mg/kg (p<0.01 and p<0.05, respectively) compared with the MTX-alone group. Overall, antiinflammatory activity was observed in rats with MTX-induced intestinal mucositis that were administered OLME. However, further studies are needed to elucidate the adverse effects of OLME.

Comparative Study to Evaluate Efficacy &amp; Cost Effectiveness of Olmesartan Versus Telmisartan, in Patients of Stage I Hypertension

Background: Hypertension is one of the most common diseases in the world. It is an important and independent risk factor for atherosclerosis, heart failure, renal disease, and peripheral arterial disease. It is directly responsible for 57% of all stroke deaths and 42% of coronary heart disease deaths in India. Objectives: To evaluate and compare efficacy and cost effectiveness in hypertensive patients receiving Olmesartan and Telmisartan in Stage I hypertension. Material and methods: The present study was an open, prospective, randomized, parallel group comparative study conducted in 60 patients of stage I hypertension over a period of 16 weeks. Patients were randomly allocated to two, age and sex, matched groups of 30 patients each. Group I patients were started on Olmesartan at a dose of 20 mg&Group II patients were put on Telmisartan at a dose of 40 mg. The BP lowering efficacy and cost effective analysis of Olmesartan versus Telmisartan was calculated&compared. The data was entered in Microsoft excel and compiled. Statistical analysis was done using various tests. Results: Maximum patients in both the groups were in age group of 51-60 years. In group I there were 13 males and 17 females. In group II there were 14 males and 16 females. Both Olmesartan and Telmisartan are effective in lowering systolic&diastolic BP in supine&sitting positions&mean BP is also lowerer, more in Olmesartan group. By cost effective analysis Telmisartan was found more cost effective. Incremental cost effective ratio was found to be 218.35. Conclusion: Both Olmesartan and Telmisartan belong to the same antihypertensive drug class, effectively reduce systolic and diastolic blood pressure at various visits. Taking into account Total cost Telmisartan was more cost effective than Olmesartan. ICER was found to be 218.35.

Effects of olmesartan therapy on the expression of lung adrenoceptors in rats with chronic heart failure.

Adrenergic receptors (AR) play important roles in regulating lung function. However, there are few reports concerning AR expression and the protective effect of angiotensin II receptor blockers (ARB) on the lung in chronic heart failure (CHF). In this study, we aimed to investigate the protective effects of the ARB olmesartan on the lung in CHF. Wistar rats were randomly divided into four groups: normal control, sham-operated rats, rats with CHF induced by ligating the left anterior descending coronary arteries, and rats with CHF treated with olmesartan (1 mg/kg) once daily for 8 weeks. Heart function, plasma renin activity (PRA) and angiotensin II (Ang II) levels, lung microscopic structure inspection and mRNA and protein expressions of α1A-, β1- and β2-AR in lung were tested. Compared with the CHF group, PRA and Ang II levels were decreased while heart function and mRNA and protein expression of α1A-AR, β1-AR and β2-AR were up-regulated in the olmesartan group (p<0.05 or p<0.01). The inflammation and cell proliferation in CHF lung tissue were reduced in the olmesartan group. Olmesartan may play a beneficial role in protecting lung in CHF by up-regulating AR and decreasing levels of PRA and Ang II.

Prevention of electrocardiographic left ventricular remodeling by the angiotensin receptor blocker olmesartan in patients with type 2 diabetes.

To assess the ability of olmesartan (OLM) to prevent or delay left ventricular remodeling and hypertrophy in patients with type 2 diabetes. This prespecified ECG substudy of Randomised OlmesArtan and Diabetes MicroAlbuminuria Prevention (ROADMAP), which compared OLM with placebo, assessed the signs of left ventricular remodeling in patients with a 12-lead ECG at baseline and after at least 2 years. Cornell voltage QRS duration product (primary objective), Cornell voltage index and Sokolow-Lyon index were assessed. In total, 9418 ECG recordings and 1513 patients from ROADMAP were analyzed (placebo, n = 736; OLM, n = 777). Quartiles defined by baseline Cornell voltage QRS duration product were assessed and the proportion of patients in the highest quartile (≥200 mVms) increased from 24.0 to 26.5% in the placebo group and decreased from 25.5 to 22.3% in the OLM group [odds ratio (OR) 0.598 (95% confidence interval [CI] 0.440-0.813); P = 0.0011]. The OR did not change after adjustment for baseline parameters. By the end of study, 38.7% of patients in the placebo group and 34.7% in the OLM group shifted from a lower to a higher quartile or remained in the highest quartile of Cornell voltage QRS duration product [OR 0.797 (95% CI 0.637-0.996); P = 0.0465]. This translated into a 20.3% risk reduction with OLM and suggested OLM attenuated the progression of left ventricular remodeling versus placebo. OLM substantially delayed the development of left ventricular remodeling in type 2 diabetes. This effect was not explained by the differences in blood pressure control. Thus, OLM delayed the onset of microalbuminuria, as well as the ECG signs of cardiac structural adaptation in type 2 diabetes.