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Effect of telmisartan on histological activity and fibrosis of non-alcoholic steatohepatitis: A 1-year randomized control trial.
Alam, S, Kabir, J, Mustafa, G, Gupta, U, Hasan, SK, Alam, AK
Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association. 2016;(1):69-76
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Abstract
BACKGROUND/AIM: Telmisartan can attenuate two hit pathogenesis of non-alcoholic steatohepatitis (NASH). This study aimed to observe the effect of Telmisartan on non-alcoholic fatty liver disease (NAFLD) activity score (NAS) and fibrosis score in NASH patients. PATIENTS AND METHODS A total of 50 NASH patients were randomized; 35 of group 1 were treated with Telmisartan 40/80 mg once daily with life style modification (TL) and 15 of group 2 underwent only life style modification (L) for 1 year. At the end, 20 of TL group and 10 of L group were analyzed. Those who showed NAS improvement ≥ 2 or NAS improvement ≥ 1 with fibrosis improvement ≥ 1 were considered as responders. RESULTS Baseline alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin resistance index, components of metabolic syndrome, age, and sex were similar in both groups. At the end of study, NAS improvement in TL and L groups was 2.15 ± 1.66 and 1.10 ± 0.57 (P = 0.017) and fibrosis improvement was 0.65 ± 0.93 and -0.30 ± 0.48 (P = 0.001), respectively. NAS improved by ≥ 2 in 13 (65%) and 2 (20%) patients and fibrosis score improved by ≥ 1 in 8 (40%) patients and none of the patients in TL group and L group, respectively. Telmisartan and life style modification could improve steatosis, ballooning, lobular inflammation, and fibrosis. Life style modification could improve ballooning only, but fibrosis deteriorated. TL group showed improvement in NAS and fibrosis score [P value: 0.035; odds ratio (OR) =92.07, confidence interval (CI) =1.39-6106] to the level of response by regression analysis. Weight reduction and improvement of metabolic syndrome did not influence the response. There were similar minor adverse events in both groups. CONCLUSION Telmisartan improved NAS and fibrosis score in NASH with insignificant adverse events.
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Effect of tablets with a combination of telmisartan and amlodipine on patients with hypertension: the Cotalo study.
Ohishi, M, Kawai, T, Hayashi, N, Kitano, S, Katsuya, T, Nagano, M, Hirotani, A, Yamamoto, K, Kamide, K, Rakugi, H
Hypertension research : official journal of the Japanese Society of Hypertension. 2013;(7):620-6
Abstract
Fixed-dose combination (FDC) therapy with telmisartan 40 mg+amlodipine 5 mg (T40/A5) is expected to achieve tight blood pressure (BP) control because of the strong efficacy and long half-life of each drug. The aims of this study were to evaluate the 24-h antihypertensive efficacy of T40/A5 FDC therapy and to explore differences that may arise owing to different administration times in Japanese patients whose hypertension was not controlled by 5 mg of amlodipine per day. In this randomized clinical trial, 44 patients who had been taking amlodipine 5 mg per day and did not achieve their optimal BP target were enrolled (mean age: 67.8±10.2 years). The subjects were then randomly assigned to a T40/A5 morning or evening administration group (22 patients per group). At baseline and 8 weeks after randomization, we evaluated clinical BP and various laboratory values and performed ambulatory BP monitoring (ABPM). Clinical and mean BP evaluated with ABPM at 8 weeks (24 h, daytime, nighttime and early morning) were significantly decreased compared with BP at baseline. There were no significant differences in the diurnal BP profile change from baseline to 8 weeks between subjects in the morning and evening administration groups. There were also no significant differences in the diurnal BP profile change from baseline to 8 weeks between subjects with or without metabolic syndrome. We conclude that T40/A5 FDC therapy significantly decreased the 24-h mean and clinical BP, independent of administration time, in patients whose hypertension was not controlled by 5 mg of amlodipine.
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Angiotensin II receptor blockers improve endothelial dysfunction associated with sympathetic hyperactivity in metabolic syndrome.
Kishi, T, Hirooka, Y, Konno, S, Sunagawa, K
Journal of hypertension. 2012;(8):1646-55
Abstract
OBJECTIVES Renin-angiotensin system inhibitors are preferred for the treatment of hypertension with metabolic syndrome (MetS). Underlying endothelial dysfunction and sympathetic nervous system (SNS) activation are critically involved in the pathogenesis of hypertension in MetS. We investigated whether treatment with angiotensin II type 1 receptor blockers (ARBs) improves endothelial and autonomic function in patients with MetS. METHODS AND RESULTS We conducted a prospective, randomized, open-label, blinded endpoint trial. Sixty patients with MetS were randomized into three treatment groups: telmisartan, candesartan, or diet therapy (control; n = 20 each), and treated for 6 months. To evaluate the endothelial function of forearm resistance arteries, blood flow and vascular resistance were measured using a strain-gauge plethysmograph during intra-arterial infusion of acetylcholine (ACh) or sodium nitroprusside (SNP). At 6 months, both telmisartan and candesartan comparably decreased blood pressure. Furthermore, ARB treatment ameliorated impaired forearm vasodilation in response to ACh. Telmisartan had a greater effect than candesartan on ACh-induced forearm vasodilation. In contrast, forearm vasodilation in response to SNP was comparable between the telmisartan and candesartan-treated groups. ARB treatment increased high-molecular-weight (HMW) adiponectin levels and baroreflex sensitivity, but telmisartan had a stronger effect than candesartan. In addition, only telmisartan treatment significantly decreased plasma norepinephrine concentrations, blood pressure variability, and heart rate variability based on spectral analysis. CONCLUSION These findings indicate that ARBs improve impaired endothelial and baroreflex function, and increase HMW adiponectin levels in patients with MetS. Telmisartan exhibited more beneficial effects than candesartan, and only telmisartan reduced sympathetic hyperactivity, despite similar depressor effects.
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Role of angiotensin II in plasma PAI-1 changes induced by imidapril or candesartan in hypertensive patients with metabolic syndrome.
Fogari, R, Zoppi, A, Mugellini, A, Maffioli, P, Lazzari, P, Derosa, G
Hypertension research : official journal of the Japanese Society of Hypertension. 2011;(12):1321-6
Abstract
To evaluate the relationship between plasma plasminogen activator inhibitor-1 (PAI-1) and angiotensin II (Ang II) changes during treatment with imidapril and candesartan in hypertensive patients with metabolic syndrome. A total of 84 hypertensive patients with metabolic syndrome were randomized to imidapril 10 mg or candesartan 16 mg for 16 weeks. At weeks 4 and 8, there was a dose titration to imidapril 20 mg and candesartan 32 mg in nonresponders (systolic blood pressure (SBP) >140 and/or diastolic blood pressure (DBP) >90 mm Hg). We evaluated, at baseline and after 2, 4, 8, 12 and 16 weeks, clinic blood pressure, Ang II and PAI-1 antigen. Both imidapril and candesartan induced a similar SBP/DBP reduction (-19.4/16.8 and -19.5/16.3 mm Hg, respectively, P<0.001 vs. baseline). Both drugs decreased PAI-1 antigen after 4 weeks of treatment, but only the PAI-1 lowering effect of imidapril was sustained throughout the 16 weeks (-9.3 ng ml(-1), P<0.01 vs. baseline), whereas candesartan increased PAI-1 (+6.5 ng ml(-1), P<0.05 vs. baseline and P<0.01 vs. imidapril). Imidapril significantly decreased Ang II levels (-14.6 pg ml(-1) at week 16, P<0.05 vs. baseline), whereas candesartan increased them (+24.2 pg ml(-1), P<0.01 vs. baseline and vs. imidapril). In both groups there was a positive correlation between Ang II and PAI-1 changes (r=0.61, P<0.001 at week 16 for imidapril, and r=0.37, P<0.005 at week 16 for candesartan). Imidapril reduced plasma PAI-1 and Ang II levels, whereas candesartan increased them. This suggests that the different effect of angiotensin-converting enzyme inhibitors and Ang II blockers on Ang II production has a role in their different influence on fibrinolysis.
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[Comprehensive management of cardiovascular risk. Focusing on telmisartan].
Ceska, R, Krutská, S, Zlatohlávek, L, Vrablík, M
Vnitrni lekarstvi. 2010;(8):839-44
Abstract
Cardiovascular diseases (CVD) represent a significant health problem in all countries world-wide and in the developed world, including the Czech Republic, in particular. The underlying cause in the majority of CVD patients is atherosclerosis and its complications, respectively. The present paper focuses on prevention and timely treatment of atherosclerosis. Management should be comprehensive and should target the risk factors (RF). Hypertension, hyperlipoproteinaemia and dyslipidemia (HLP and DLP), type 2 diabetes mellitus (T2DM), visceral fat obesity and cigarette smoking are the dominating RFs. Even though all RFs have to be managed simultaneously and it is not possible to focus on just one of them, for the sake of clarity, this paper discusses hypertension and the use of telmisartan, a representative of one the most up-to-date group of antihypertensives. There is a growing evidence that it is not always just a reduction of a specific risk that is important but also the mode of treatment. For example, to reduce a CV risk in a patient with hypertension but also, for example, with metabolic syndrome, it is more beneficial to treat the patient with rennin-angiotensin system (RAS) blocking agents, possibly in a combination with calcium channels antagonists, than to use "traditional" (older) treatment approach with a combination of a beta/blocker and diuretic. Among the RAS-modifying agents, ACE inhibitors and sartans are the most widely used. Among sartans, telmisartan is very well-tolerated and has evidence from a large interventional study for its effect on reducing the CV risk.
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Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis.
Georgescu, EF, Ionescu, R, Niculescu, M, Mogoanta, L, Vancica, L
World journal of gastroenterology. 2009;(8):942-54
Abstract
AIM: To evaluate insulin resistance, cytolysis and non-alcoholic steatohepatitis (NASH) score (NAS) using the Kleiner and Brunt criteria in 54 patients with NASH and mild-to-moderate hypertension, treated with telmisartan vs valsartan for 20 mo. METHODS All patients met the NCEP-ATP III criteria for metabolic syndrome. Histology confirmed steatohepatitis, defined as a NAS greater than five up to 3 wk prior inclusion, using the current criteria. Patients with viral hepatitis, chronic alcohol intake, drug abuse or other significant immune or metabolic hepatic pathology were excluded. Subjects were randomly assigned either to the valsartan (V) group (standard dose 80 mg o.d., n = 26), or to the telmisartan (T) group (standard dose 20 mg o.d., n = 28). Treatment had to be taken daily at the same hour with no concomitant medication or alcohol consumption allowed. Neither the patient nor the medical staff was aware of treatment group allocation. Paired liver biopsies obtained at inclusion (visit 1) and end of treatment (EOT) were assessed by a single blinded pathologist, not aware of patient or treatment group. Blood pressure, BMI, ALT, AST, HOMA-IR, plasma triglycerides (TG) and total cholesterol (TC) were evaluated at inclusion and every 4 mo until EOT (visit 6). RESULTS At EOT we noticed a significant decrease in ALT levels vs inclusion in all patients and this decrease did not differ significantly in group T vs group V. HOMA-IR significantly decreased at EOT vs inclusion in all patients but in group T, the mean HOMA-IR decrease per month was higher than in group V. NAS significantly diminished at EOT in all patients with a higher decrease in group T vs group V. CONCLUSION Angiotensin receptor blockers seem to be efficient in hypertension-associated NASH. Telmisartan showed a higher efficacy regarding insulin resistance and histology, perhaps because of its specific PPAR-gamma ligand effect.
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Treatment of hypertension in individuals with the cardiometabolic syndrome: role of an angiotensin II receptor blocker, telmisartan.
Francischetti, EA, Celoria, BM, Francischetti, A, Genelhu, VA
Expert review of cardiovascular therapy. 2008;(3):289-303
Abstract
Arterial hypertension is a global public health problem owing to its high prevalence and association with increased risk for cerebral, cardiac and renal events. Hypertension frequently clusters with other cardiometabolic risk factors, such as dysglycemia, low levels of high-density lipoprotein cholesterol and high triglyceride levels. These, along with other factors such as central obesity, increased inflammation, endothelial dysfunction and thrombosis, are components of the metabolic syndrome. All guidelines recommend that the first-line therapy in metabolic syndrome should be based on lifestyle modification, consisting of diet and moderate exercise for at least 30 min/day. Concerning drug treatment of hypertension associated with other cardiometabolic risk factors, many results of head-to-head studies have demonstrated a reduction in new-onset Type 2 diabetes in hypertensive patients treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, when compared with conventional antihypertensive therapy. The explanations of the different actions of both these drugs include several mechanisms related to pancreatic insulin release and insulin sensitivity improvement. Another mechanism by which the inhibition of the renin-angiotensin system may improve insulin sensitivity is through the partial peroxisome proliferator-activated receptor-gamma agonism of telmisartan. For that reason, telmisartan has been considered by some experts to be an antihypertensive agent that is particularly useful in the treatment of hypertension associated with cardiometabolic risk factors. The impact of the promising metabolic action exhibited by telmisartan on the outcome of hypertensive patients aggregating other cardiometabolic risk factors waits for adequately randomized and powered clinical trials.
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Effects of telmisartan on fat distribution in individuals with the metabolic syndrome.
Shimabukuro, M, Tanaka, H, Shimabukuro, T
Journal of hypertension. 2007;(4):841-8
Abstract
BACKGROUND Visceral fat obesity plays an essential role in the clustering of atherosclerotic multiple risk factors in the metabolic syndrome. Telmisartan, an angiotensin II type 1 receptor blocker, has partial agonistic properties for peroxisome proliferator-activated receptor gamma, which is a key regulator of adipocyte differentiation and function. METHODS This study aimed to clarify the impact of telmisartan on fat distribution and insulin sensitivity in the metabolic syndrome. In this open-label, prospective, randomized study, patients with the metabolic syndrome (waist circumference: men >or= 85 cm, women >or= 90 cm) were treated either with amlodipine (n = 26) or with telmisartan (n = 27) for 24 weeks, and fat distribution and insulin sensitivity were determined. RESULTS Systolic and diastolic blood pressure were decreased in both groups to a comparable level. However, insulin and glucose levels during an oral 75 g glucose loading were decreased only in the telmisartan group. The visceral fat area, determined by abdominal computed tomography scan, was reduced in the telmisartan group after 24 weeks' treatment, but the subcutaneous fat area did not change in either group. CONCLUSION The results imply that telmisartan could treat both the hemodynamic and metabolic aberrations seen in patients with the metabolic syndrome, improving insulin resistance and glucose intolerance at least partly through visceral fat remodeling.
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Effects of telmisartan and losartan on insulin resistance in hypertensive patients with metabolic syndrome.
Bahadir, O, Uzunlulu, M, Oguz, A, Bahadir, MA
Hypertension research : official journal of the Japanese Society of Hypertension. 2007;(1):49-53
Abstract
Partial peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists are known to decrease insulin resistance. Experimental studies have shown that the angiotensin type 1 receptor blocker (ARB) telmisartan has a PPAR-gamma-activating property, but there does not appear to be a class effect. To test telmisartan's clinical importance, we here investigated its effect on insulin resistance in hypertensive patients with metabolic syndrome (MetS) in comparison with another ARB, losartan. A total of 42 hypertensive MetS patients (29 female, 13 male) were included (mean age: 50+/-9, range: 20-70 years). NCEP-ATP III criteria were used for the diagnosis of MetS. Patients were randomized to receive either telmisartan 80 mg/day (n=21) or losartan 50 mg/day (n=21) for 8 weeks. Biochemical assessments were made at baseline and at the end of the 8 weeks. Insulin resistance was evaluated by using homeostasis model assessment of insulin resistance (HOMA-IR). Both groups had similar reductions in systolic and diastolic pressures (p>0.05). HOMA-IR did not change significantly in either group throughout the study. In the telmisartan group, the mean HOMA-IR at baseline and at the end of the study were 1.9+/-07 and 1.9+/-0.5, respectively. The figures for the losartan group were 1.8+/-0.6 and 1.8+/-0.6, corresponding. In conclusion, in contrast with the reports that telmisartan may decrease insulin resistance by an effect associated with its molecular structure, 8 weeks of telmisartan treatment in the present study had a neutral effect on insulin resistance in hypertensive MetS patients, and similar results were obtained for losartan.
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Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha.
Derosa, G, Cicero, AF, D'Angelo, A, Ragonesi, PD, Ciccarelli, L, Piccinni, MN, Pricolo, F, Salvadeo, SA, Ferrari, I, Gravina, A, et al
Hypertension research : official journal of the Japanese Society of Hypertension. 2006;(11):849-56
Abstract
The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.