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Thomas Unger - One of the best experts on this subject based on the ideXlab platform.
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impact of Telmisartan on cardiovascular outcome in hypertensive patients at high risk a Telmisartan randomised assessment study in ace intolerant subjects with cardiovascular disease subanalysis
Journal of Hypertension, 2014Co-Authors: Sebastien Foulquier, Roland E. Schmieder, Peter Sleight, Michael Bohm, Salim Yusuf, Helmut Schumacher, Thomas UngerAbstract:BACKGROUND: In the Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease, all patients were at high cardiovascular risk, and a substantial proportion were hypertensive. We performed a post-hoc analysis to explore the hypothesis that Telmisartan has a differential action in hypertensive vs. nonhypertensive patients. METHODS: The primary four-fold endpoint (composite of cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for heart failure), the secondary three-fold endpoint (cardiovascular death, MI, and stroke), the individual components, new onset of left ventricular hypertrophy (LVH), and new onset of albuminuria were analyzed. RESULTS: There was no evidence for a significantly differential treatment effect of Telmisartan in hypertensive and nonhypertensive patients for any endpoints, although the occurrence of the secondary three-fold endpoint was significantly lower in the Telmisartan group (13.0%) compared with placebo (15.0%, P < 0.05) only in hypertensive patients. Moreover, data from this post-hoc analysis suggest that MI may be less frequent in hypertensive patients treated with Telmisartan (3.8 vs. 5.1%; P < 0.05). Telmisartan may also reduce new onset of LVH (nonhypertensive patients P < 0.05; hypertensive patients P < 0.001) in both subgroups, and new onset of microalbuminuria and macroalbuminuria in hypertensive patients (P < 0.001 and P < 0.01, respectively).The effect of Telmisartan in hypertensive and nonhypertensive patients at high cardiovascular risk was not different. This post-hoc analysis suggests that MI may be further reduced by Telmisartan in hypertensive patients. Further investigations are needed to study the hypotheses raised by this explanatory analysis.
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Telmisartan and hydrochlorothiazide combination therapy for the treatment of hypertension
Current Medical Research and Opinion, 2010Co-Authors: Sverre E. Kjeldsen, Thomas Unger, Roland E. Schmieder, Giuseppe ManciaAbstract:AbstractBackground:Control of elevated blood pressure has been shown to reduce the risk of cardiovascular events. The angiotensin II receptor blocker (ARB), Telmisartan, has been shown to provide effective 24-hour blood pressure control. Additional antihypertensive efficacy can be achieved by combining Telmisartan with the thiazide diuretic hydrochlorothiazide (HCTZ).Objective:To review the clinical data in combination therapy with Telmisartan and HCTZ.Methods:Search of Medline and Embase for published clinical studies using the keywords Telmisartan and HCTZ.Findings:The Telmisartan/HCTZ combination provides significant reductions in blood pressure, effective 24-hour blood pressure control and is well-tolerated. Blood pressure reductions with this combination are greater than those achieved with either drug alone, and in comparative studies Telmisartan/HCTZ is more effective than other ARB/HCTZ combinations. However, it should be noted that some of the combinations assessed used doses of the drugs that we...
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liver specific peroxisome proliferator activated receptor α target gene regulation by the angiotensin type 1 receptor blocker Telmisartan
Diabetes, 2008Co-Authors: M Clemenz, Nikolaj Frost, Michael Schupp, Sandrine Caron, Anna Forystludwig, Christian Bohm, Martin Hartge, Ronald Gust, Bart Staels, Thomas UngerAbstract:Objective: The angiotensin type 1 receptor blocker (ARB) and PPARγ-modulator Telmisartan has been recently demonstrated to reduce plasma triglycerides in non-diabetic and diabetic hypertensive patients. The present study investigates the molecular mechanisms of Telmisartans hypolipidemic actions, in particular its effect on the PPARα pathway. Research Design and Methods: Regulation of PPARα-target genes by Telmisartan was studied by real-time PCR and Western immunoblotting in-vitro and in-vivo in liver/skeletal muscle of mice with diet-induced obesity (DIO). Activation of the PPARα-ligand binding domain (LBD) was investigated using transactivation assays. Results: Telmisartan significantly induced the PPARα target genes carnitine palmitoyl transferase 1A (CPT1A) in human HepG2 cells and acyl-CoA synthetase long-chain family member 1 (ACSL1) in murine AML12 cells in the μ-molar range. Telmisartan-induced CPT1A stimulation was markedly reduced after siRNA-mediated knockdown of PPARα. Telmisartan consistently activated the PPARα-LBD as a partial PPARα agonist. Despite high in-vitro concentrations required for PPARα activation, Telmisartan (3mg/kg/d) potently increased ACSL1 and CPT1A expression in liver from DIO-mice associated with a marked decrease of hepatic- and serum triglycerides. Muscular CPT1B expression was not affected. Tissue specificity of Telmisartan-induced PPARα-target gene induction may be the result of previously reported high hepatic concentrations of Telmisartan. Conclusions: The present study identifies the ARB/PPARγ modulator Telmisartan as a partial PPARα agonist. As a result of its particular pharmacokinetic profile, PPARα activation by Telmisartan seems to be restricted to the liver. Hepatic PPARα activation may provide an explanation for Telmisartan's anti-dyslipidemic actions observed in recent clinical trials.
Yuichi Sugiyama - One of the best experts on this subject based on the ideXlab platform.
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whole body distribution and radiation dosimetry of 11c Telmisartan as a biomarker for hepatic organic anion transporting polypeptide oatp 1b3
Nuclear Medicine and Biology, 2012Co-Authors: Keiji Shimizu, Tadayuki Takashima, Yoshinobu Hashizume, Kazuya Maeda, Yuichi Sugiyama, Yasuyoshi Watanabe, Masahiro Sasaki, Tomohiko Yamane, Hiromitsu Kageyama, Michio SendaAbstract:Abstract Introduction Telmisartan, a nonpeptide angiotensin II AT1 receptor antagonist used as an antihypertensive drug, is specifically taken up by the liver through the OATP1B3. PET imaging with [ 11 C]Telmisartan is expected to provide information about the whole body pharmacokinetics of Telmisartan as well as its transport property by OATP1B3. The purpose of the study was to determine the biodistribution and radiation dosimetry of [ 11 C]Telmisartan in humans. Methods Biodistribution of [ 11 C]Telmisartan was measured in three rats and six healthy male human volunteers. In the rat study, a dynamic emission scan was performed for 90 min. In the human study, dynamic whole-body PET images were acquired after intravenous injection of [ 11 C]Telmisartan. ROIs were defined for source organs on the PET images to measure time-course of [ 11 C]Telmisartan uptake as percentage injected dose and the number of disintegration for each organ. Radiation dosimetry was calculated with OLINDA/EXM. Results In the rat study, most radioactivity was rapidly taken up by the liver and part of it was excreted into the biliary tract and intestine. Extrapolating from the rat data, the effective dose for the adult human being was estimated to be 3.65±0.01 microSv/MBq ( n =3). In the human study, most of the tracer was taken up by the liver as well, although not as rapidly as in the rat. The activity in the gall bladder and intestine increased gradually. The effective dose for the adult human being was 4.24±0.09 microSv/MBq ( n =6). Conclusions [ 11 C]Telmisartan is a safe PET tracer with a dosimetry profile comparable to other common 11 C PET tracers.
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The Involvement of Organic Anion Transporting Polypeptide in the Hepatic Uptake of Telmisartan in Rats: PET Studies with [11C]Telmisartan
Molecular Pharmaceutics, 2011Co-Authors: Tadayuki Takashima, Yoshinobu Hashizume, Yumiko Katayama, Machiko Murai, Yasuhiro Wada, Kazuya Maeda, Yuichi Sugiyama, Yasuyoshi WatanabeAbstract:Telmisartan, a selective angiotensin II receptor antagonist, is primarily excreted via hepatobiliary transport. The predominant contribution of organic anion transporting polypeptide (OATP) 1B3 in its hepatic uptake of Telmisartan has been demonstrated by in vitro transport studies. In the present study, a quantitative positron emission tomography (PET) methodology was developed for in vivo kinetic assessment of hepatobiliary transport of Telmisartan. Serial abdominal PET scans were performed in rats following intravenous administration of [11C]Telmisartan as a radiotracer. PET scans revealed that [11C]Telmisartan was localized primarily in the liver and some of the radioactivity moved to the intestine, which corresponds to biliary excretion. Radiometabolite analysis by radiometric HPLC showed that [11C]Telmisartan was converted to its acylglucuronide, which was mainly detected in bile, but little in plasma and liver. Integration plot analysis revealed that [11C]Telmisartan was taken up into the liver as ...
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first automatic radiosynthesis of 11c labeled Telmisartan using a multipurpose synthesizer for clinical research use
Annals of Nuclear Medicine, 2011Co-Authors: Hitoshi Iimori, Yoshinobu Hashizume, Yuichi Sugiyama, Yasuyoshi Watanabe, Masahiro Sasaki, Yoshinobu Kajiwara, Yuichi Sugimoto, Michio SendaAbstract:Objective Telmisartan, a nonpeptide angiotensin II AT1 receptor antagonist, is an antihypertensive drug. Positron emission tomography (PET) imaging with [11C]Telmisartan is expected to provide information about the whole body pharmacokinetics of Telmisartan as well as the transport function of hepatic OATP1B3. We developed a first automatic preparation system of [11C]Telmisartan to applicable clinical research using a new 11C and 18F multipurpose synthesizer.
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predominant contribution of oatp1b3 to the hepatic uptake of Telmisartan an angiotensin ii receptor antagonist in humans
Drug Metabolism and Disposition, 2006Co-Authors: Naoki Ishiguro, Kazuya Maeda, Thomas Ebner, Wataru Kishimoto, Asami Saito, Akiko Harada, Willy Roth, Takashi Igarashi, Yuichi SugiyamaAbstract:Telmisartan, a nonpeptide angiotensin II receptor antagonist, is selectively distributed to liver. In the present study, we have characterized the contribution of organic anion transporting polypeptide (OATP) isoforms to the hepatic uptake of Telmisartan by isolated rat hepatocytes, human cryopreserved hepatocytes, and human transporter-expressing cells. Because it is difficult to evaluate the transport activity of Telmisartan because of its extensive adsorption to cells and culture materials, we performed the uptake study in the presence of human serum albumin. The saturable uptake of Telmisartan into isolated rat hepatocytes took place in a Na + -independent manner and was inhibited by pravastatin, taurocholate, and digoxin, which are Oatp substrates and inhibitors, but not by organic cation, tetraethylammonium, indicating the involvement of Oatp isoforms in its uptake into rat hepatocytes. To identify which human OATP transporters are important for the hepatic uptake of Telmisartan, the uptake assay was carried out using OATP1B1- and OATP1B3-expressing human embryonic kidney 293 cells and cryopreserved human hepatocytes. The uptake of Telmisartan by OATP1B3-expressing cells was saturable ( K m = 0.81 μM) and significantly higher than that by vector-transfected cells. In contrast, no significant uptake was observed in OATP1B1-expressing cells. We also observed the saturable uptake of Telmisartan by human hepatocytes. Thirty micromolar estrone-3-sulfate, which can selectively inhibit OATP1B1-mediated uptake compared with OATP1B3, did not inhibit the uptake of Telmisartan in human hepatocytes, whereas it could inhibit the uptake of estradiol 17β-d-glucuronide mediated by OATP1B1. These results suggest that OATP1B3 is predominantly involved in the hepatic uptake of Telmisartan in humans.
Juan M Saavedra - One of the best experts on this subject based on the ideXlab platform.
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Telmisartan prevention of lps induced microglia activation involves m2 microglia polarization via camkkβ dependent ampk activation
Brain Behavior and Immunity, 2015Co-Authors: Yuan Xu, Yazhou Xu, Yurong Wang, Yunjie Wang, Ling He, Zhenzhou Jiang, Zhangjian Huang, Hong Liao, Jia Li, Juan M SaavedraAbstract:Abstract Brain inflammation plays an important role in the pathophysiology of many psychiatric and neurological diseases. During brain inflammation, microglia cells are activated, producing neurotoxic molecules and neurotrophic factors depending on their pro-inflammatory M1 and anti-inflammatory M2 phenotypes. It has been demonstrated that Angiotensin II type 1 receptor blockers (ARBs) ameliorate brain inflammation and reduce M1 microglia activation. The ARB Telmisartan suppresses glutamate-induced upregulation of inflammatory genes in cultured primary neurons. We wished to clarify whether Telmisartan, in addition, prevents microglia activation through polarization to an anti-inflammatory M2 phenotype. We found that Telmisartan promoted M2 polarization and reduced M1 polarization in LPS-stimulated BV2 and primary microglia cells, effects partially dependent on PPARγ activation. The promoting effects of Telmisartan on M2 polarization, were attenuated by an AMP-activated protein kinase (AMPK) inhibitor or AMPK knockdown, indicating that AMPK activation participates on Telmisartan effects. Moreover, in LPS-stimulated BV2 cells, Telmisartan enhancement of M2 gene expression was prevented by the inhibitor STO-609 and siRNA of calmodulin-dependent protein kinase kinase β (CaMKKβ), an upstream kinase of AMPK. Furthermore, Telmisartan enhanced brain AMPK activation and M2 gene expression in a mouse model of LPS-induced neuroinflammation. In addition, Telmisartan reduced the LPS-induced sickness behavior in this in vivo model, and this effect was prevented by prior administration of an AMPK inhibitor. Our results indicate that Telmisartan can be considered as a novel AMPK activator, suppressing microglia activation by promoting M2 polarization. Telmisartan may provide a novel, safe therapeutic approach to treat brain disorders associated with enhanced inflammation.
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Telmisartan ameliorates glutamate induced neurotoxicity roles of at1 receptor blockade and pparγ activation
Neuropharmacology, 2014Co-Authors: Juan Wang, Juan M Saavedra, Tao Pang, Roman Hafko, Julius Benicky, Enrique SanchezlemusAbstract:Abstract Sartans (Angiotensin II AT1 Receptor Blockers, ARBs) are powerful neuroprotective agents in vivo and protect against IL-1β neurotoxicity in vitro. The purpose of this research was to determine the extent of sartan neuroprotection against glutamate excitotoxicity, a common cause of neuronal injury and apoptosis. The results show that sartans are neuroprotective, significantly reducing glutamate-induced neuronal injury and apoptosis in cultured rat primary cerebellar granule cells (CGCs). Telmisartan was the most potent sartan studied, with an order of potency Telmisartan > candesartan > losartan > valsartan. Mechanisms involved reduction of pro-apoptotic caspase-3 activation, protection of the survival PI3K/Akt/GSK-3β pathway and prevention of glutamate-induced ERK1/2 activation. NMDA receptor stimulation was essential for glutamate-induced cell injury and apoptosis. Participation of AT1A receptor was supported by glutamate-induced upregulation of AT1A gene expression and AT1 receptor binding. Conversely, AT1B or AT2 receptors played no role. Glutamate-induced neuronal injury and the neuroprotective effect of Telmisartan were decreased, but not abolished, in CGCs obtained from AT1A knock-out mice. This indicates that although AT1 receptors are necessary for glutamate to exert its full neurotoxic potential, part of the neuroprotective effect of Telmisartan is independent of AT1 receptor blockade. PPARγ activation was also involved in the neuroprotective effects of Telmisartan, as Telmisartan enhanced PPARγ nuclear translocation and the PPARγ antagonist GW9662 partially reversed the neuroprotective effects of Telmisartan. The present results substantiate the therapeutic use of sartans, in particular Telmisartan, in neurodegenerative diseases and traumatic brain disorders where glutamate neurotoxicity plays a significant role.
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Telmisartan directly ameliorates the neuronal inflammatory response to il 1β partly through the jnk c jun and nadph oxidase pathways
Journal of Neuroinflammation, 2012Co-Authors: Tao Pang, Juan Wang, Julius Benicky, Enrique Sanchezlemus, Juan M SaavedraAbstract:Blockade of angiotensin II type 1 (AT1) receptors ameliorates brain inflammation, and reduces excessive brain interleukin-1 beta (IL-1β) production and release from cortical microglia. The aim of this study was to determine whether, in addition, AT1 receptor blockade directly attenuates IL-1β-induced inflammatory responses in neuronal cultures. SK-N-SH human neuroblasts and primary rat cortical neurons were pretreated with Telmisartan followed by exposure to IL-1β. Gene expression was determined by reverse transcriptase (RT)-PCR, protein expression and kinase activation by western blotting, NADPH oxidase activity by the lucigenin method, prostaglandin E2 (PGE2) release by enzyme immunoassay, reactive oxygen species (ROS) generation by the dichlorodihydrofluorescein diacetate fluorescent probe assay, and peroxisome proliferator-activated receptor gamma (PPARγ) involvement was assessed with the antagonists GW9662 and T0070907, the agonist pioglitazone and the expression of PPARγ target genes ABCG1 and CD36. We found that SK-N-SH neuroblasts expressed AT1 but not AT2 receptor mRNA. Telmisartan reduced IL-1β-induced cyclooxygenase-2 (COX-2) expression and PGE2 release more potently than did candesartan and losartan. Telmisartan reduced the IL-1β-induced increase in IL-1R1 receptor and NADPH oxidase-4 (NOX-4) mRNA expression, NADPH oxidase activity, and ROS generation, and reduced hydrogen peroxide-induced COX-2 gene expression. Telmisartan did not modify IL-1β-induced ERK1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation or nuclear factor-κB activation but significantly decreased IL-1β-induced c-Jun N-terminal kinase (JNK) and c-Jun activation. The JNK inhibitor SP600125 decreased IL-1β-induced PGE2 release with a potency similar to that of Telmisartan. The PPARγ agonist pioglitazone reduced IL-1β-induced inflammatory reaction, whereas Telmisartan did not activate PPARγ, as shown by its failure to enhance the expression of the PPARγ target genes ABCG1 and CD36, and the inability of the PPARγ antagonists GW9662 and T0070907 to modify the effect of Telmisartan on COX-2 induction. The effect of Telmisartan on IL-1β-stimulated COX-2 and IL-1R1 mRNA expression and ROS production was replicated in primary rat cortical neurons. Telmisartan directly ameliorates IL-1β-induced neuronal inflammatory response by inhibition of oxidative stress and the JNK/c-Jun pathway. Our results support the hypothesis that AT1 receptor blockers are directly neuroprotective, and should be considered for the treatment of inflammatory conditions of the brain.
Roland E. Schmieder - One of the best experts on this subject based on the ideXlab platform.
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effect of Telmisartan on renal outcomes
Annals of Internal Medicine, 2015Co-Authors: Roland E. Schmieder, Jeffrey L Probstfield, Helmut Schumacher, Leanne Dyal, Matthew J Mcqueen, Janice Pogue, Xingyu Wang, Alvaro Avezum, Ernesto German Cardonamunoz, Gilles R. DagenaisAbstract:Results: No important difference was found in the composite renal outcome with Telmisartan (58 patients [1.96%]) versus placebo (46 patients [1.55%]) (hazard ratio, 1.29 [95% CI, 0.87 to 1.89]; P 0.20). Among the Telmisartan and placebo groups, 7 and 10 patients had dialysis and 56 and 36 patients had doubling of serum creatinine, respectively (hazard ratio, 1.59 [CI, 1.04 to 2.41]; P 0.031). Albuminuria increased less with Telmisartan than with placebo (32% [CI, 23% to 41%] vs. 63% [CI, 52% to 76%]; P 0.001). Decreases in estimated GFR were greater with Telmisartan than with placebo (mean change in estimated GFR, 3.2 mL/min per 1.73 m 2 [SD, 18.3] vs. 0.26 mL/min per 1.73 m 2 [SD, 18.0];
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impact of Telmisartan on cardiovascular outcome in hypertensive patients at high risk a Telmisartan randomised assessment study in ace intolerant subjects with cardiovascular disease subanalysis
Journal of Hypertension, 2014Co-Authors: Sebastien Foulquier, Roland E. Schmieder, Peter Sleight, Michael Bohm, Salim Yusuf, Helmut Schumacher, Thomas UngerAbstract:BACKGROUND: In the Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease, all patients were at high cardiovascular risk, and a substantial proportion were hypertensive. We performed a post-hoc analysis to explore the hypothesis that Telmisartan has a differential action in hypertensive vs. nonhypertensive patients. METHODS: The primary four-fold endpoint (composite of cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for heart failure), the secondary three-fold endpoint (cardiovascular death, MI, and stroke), the individual components, new onset of left ventricular hypertrophy (LVH), and new onset of albuminuria were analyzed. RESULTS: There was no evidence for a significantly differential treatment effect of Telmisartan in hypertensive and nonhypertensive patients for any endpoints, although the occurrence of the secondary three-fold endpoint was significantly lower in the Telmisartan group (13.0%) compared with placebo (15.0%, P < 0.05) only in hypertensive patients. Moreover, data from this post-hoc analysis suggest that MI may be less frequent in hypertensive patients treated with Telmisartan (3.8 vs. 5.1%; P < 0.05). Telmisartan may also reduce new onset of LVH (nonhypertensive patients P < 0.05; hypertensive patients P < 0.001) in both subgroups, and new onset of microalbuminuria and macroalbuminuria in hypertensive patients (P < 0.001 and P < 0.01, respectively).The effect of Telmisartan in hypertensive and nonhypertensive patients at high cardiovascular risk was not different. This post-hoc analysis suggests that MI may be further reduced by Telmisartan in hypertensive patients. Further investigations are needed to study the hypotheses raised by this explanatory analysis.
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Telmisartan and hydrochlorothiazide combination therapy for the treatment of hypertension
Current Medical Research and Opinion, 2010Co-Authors: Sverre E. Kjeldsen, Thomas Unger, Roland E. Schmieder, Giuseppe ManciaAbstract:AbstractBackground:Control of elevated blood pressure has been shown to reduce the risk of cardiovascular events. The angiotensin II receptor blocker (ARB), Telmisartan, has been shown to provide effective 24-hour blood pressure control. Additional antihypertensive efficacy can be achieved by combining Telmisartan with the thiazide diuretic hydrochlorothiazide (HCTZ).Objective:To review the clinical data in combination therapy with Telmisartan and HCTZ.Methods:Search of Medline and Embase for published clinical studies using the keywords Telmisartan and HCTZ.Findings:The Telmisartan/HCTZ combination provides significant reductions in blood pressure, effective 24-hour blood pressure control and is well-tolerated. Blood pressure reductions with this combination are greater than those achieved with either drug alone, and in comparative studies Telmisartan/HCTZ is more effective than other ARB/HCTZ combinations. However, it should be noted that some of the combinations assessed used doses of the drugs that we...
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effects of Telmisartan ramipril and their combination on left ventricular hypertrophy in individuals at high vascular risk in the ongoing Telmisartan alone and in combination with ramipril global end point trial and the Telmisartan randomized assessm
Circulation, 2009Co-Authors: P Verdecchia, Roland E. Schmieder, Giuseppe Mancia, Peter Sleight, Robert Fagard, Bruno Trimarco, Garry L Jennings, Petr Jansky, Jyhhong Chen, Jeffrey L ProbstfieldAbstract:Background— Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers reduce left ventricular hypertrophy (LVH). The effect of these drugs on LVH in high-risk patients without heart failure is unknown. Methods and Results— In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), patients at high vascular risk and tolerant of ACE inhibitors were randomly assigned to ramipril, Telmisartan, or their combination (n=23 165). In the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND), patients intolerant of ACE inhibitors were randomized to Telmisartan or placebo (n=5343). Prevalence of LVH at entry in TRANSCEND was 12.7%. It was reduced by Telmisartan (10.5% and 9.9% after 2 and 5 years) compared with placebo (12.7% and 12.8% after 2 and 5 years) (overall odds ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.0017). New-onset LVH occurred less frequently with Telmisartan compared...
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effect of Telmisartan on renal outcomes a randomized trial
Annals of Internal Medicine, 2009Co-Authors: Johannes F E Mann, Roland E. Schmieder, Jeffrey L Probstfield, Helmut Schumacher, Leanne Dyal, Matthew J Mcqueen, Janice Pogue, Xingyu Wang, Alvaro Avezum, Ernesto German CardonamunozAbstract:Background: Angiotensin-receptor blockers (ARBs) blunt progression of advanced diabetic nephropathy, but their long-term renal effects in other patients are not clear. Objective: To examine the long-term renal effects of Telmisartan versus placebo in adults at high vascular risk. Design: Randomized trial. Patients were randomly assigned by a central automated system between November 2001 and May 2004 and were followed until March 2008. Participants and investigators were blinded to intervention status. Setting: Multicenter, multinational study. Patients: 5927 adults with known cardiovascular disease or diabetes with end-organ damage but without macroalbuminuria or heart failure who cannot tolerate angiotensin-converting enzyme inhibitors. Intervention: Telmisartan, 80 mg/d (n = 2954), or matching placebo (n = 2972) plus standard treatment for a mean of 56 months. Measurements: Composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated glomerular filtration rate (GFR), and changes in albuminuria. Results: No important difference was found in the composite renal outcome with Telmisartan (58 patients [1.96%]) versus placebo (46 patients [1.55%]) (hazard ratio, 1.29 [95% CI, 0.87 to 1.89]; P = 0.20). Among the Telmisartan and placebo groups, 7 and 10 patients had dialysis and 56 and 36 patients had doubling of serum creatinine, respectively (hazard ratio, 1.59 [CI, 1.04 to 2.41]; P = 0.031). Albuminuria increased less with Telmisartan than with placebo (32% [CI, 23% to 41%] vs. 63% [CI, 52% to 76%]; P < 0.001). Decreases in estimated GFR were greater with Telmisartan than with placebo (mean change in estimated GFR, ―3.2 mL/min per 1.73 m 2 [SD, 18.3] vs. ―0.26 mL/min per 1.73 m 2 [SD, 18.0]; P < 0.001). Limitation: Only 17 participants had dialysis. Conclusion: In adults with vascular disease but without macroalbuminuria, the effects of Telmisartan on major renal outcomes were similar to those of placebo. Primary Funding Source: Boehringer Ingelheim.
Kenichi Hirata - One of the best experts on this subject based on the ideXlab platform.
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Comparison of Telmisartan/amlodipine and Telmisartan/hydrochlorothiazide in the treatment of Japanese patients with uncontrolled hypertension: the TAT-Kobe study.
Blood Pressure Monitoring, 2016Co-Authors: Kensuke Kondo, Tatsuro Ishida, Kenta Mori, Tomoyuki Yasuda, Kenichi HirataAbstract:ObjectiveThe aim of this study was to compare the efficacy and safety of Telmisartan plus amlodipine with Telmisartan plus hydrochlorothiazide for the treatment of uncontrolled hypertension.MethodsJapanese hypertensive patients with uncontrolled hypertension, despite taking angiotensin II receptor b
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angiotensin ii type 1 receptor blocker Telmisartan suppresses superoxide production and reduces atherosclerotic lesion formation in apolipoprotein e deficient mice
Atherosclerosis, 2006Co-Authors: Tomofumi Takaya, Seinosuke Kawashima, Masakazu Shinohara, Tomoya Yamashita, Naoto Sasaki, Nobutaka Inoue, Kenichi Hirata, Mitsuhiro YokoyamaAbstract:Abstract Angiotensin II is involved in the process of atherosclerosis and stimulates superoxide production from cardiovascular cells. We examined the effect of Telmisartan, an angiotensin II type 1 receptor blocker, on atherosclerosis. We chronically treated apolipoprotein E-deficient mice with two different doses of Telmisartan dissolved in drinking water (0.3 and 3mg/kg) starting from 4 weeks of age for 12 weeks. Lipid contents were not different in both Telmisartan-treated groups compared with control group. Systolic blood pressure was significantly reduced with 3mg/kg, but unchanged with 0.3mg/kg. The total atherosclerotic lesion size at the aortic sinus was reduced with 0.3mg/kg compared with control, and additional reduction was proved with 3mg/kg. The fibrotic change was not different among three groups, but MOMA-2-, malondialdehyde-, 4-hydroxy-2-nonenal-immunostained areas were reduced by Telmisartan. As the mechanism, we revealed that both doses of Telmisartan markedly reduced superoxide production from in situ vessels assessed by lucigenin-enhanced chemiluminescence and dihydroethidium staining. And NAD(P)H dependent oxidase activity in vessels was reduced by Telmisartan. Further, 8- iso -prostaglandin F2α level, a systemic oxidative stress marker, obtained from urine and plasma samples were significantly reduced by Telmisartan. Telmisartan reduced atherosclerosis in apolipoprotein E-deficient mice at least partly via the suppression of oxidative stress.
