Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A prospective, randomised, double-blind, parallel group study was carried out to compare the efficacy, safety and tolerability of telmisartan 40 mg once daily with losartan 50 mg once daily in Indian patients with mild to moderate hypertension. It had a placebo run-in period of 2 weeks followed by drug treatment (telmisartan 40 mg, once daily or losartan 50 mg once daily) for 8 weeks. Supine BP was assessed at the end of every 2 weeks. Tolerability and safety was assessed by physical examination, laboratory parameters and evaluation of adverse events. Treatment with telmisartan resulted in a significant reduction of SBP of 10.3% and 13.7% as compared to 6.6% and 10.6% in losartan group at the end of 6th and 8th weeks respectively. At the end of 6th and 8th weeks, the reduction was 14.3% and 18.1% among telmisartan which was significantly more as compared to 8.8% and 14.3% in losartan group respectively. The laboratory values were within normal limits. Both drugs were well tolerated. Telmisartan monotherapy in a dose of 40 mg once daily has a clinically better therapeutic effect as compared to losartan 50 mg and a good tolerability profile in patients with mild to moderate hypertension.
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PMID:Comparison of the efficacy, safety and tolerability of telmisartan with losartan in Indian patients with mild to moderate hypertension: a pilot study. 1457 32

Kinzalkomb marketed in Belgium by Bayer is a fixed combination of telmisartan 80 mg and hydrochlorothiazide 125 mg for the treatment of hypertension. New guidelines for the treatment of hypertension were recently released both in Europe and the United States (see article by J.M. Krzesinski in this issue). They offer the choice of using a fixed biotherapy even as first line treatment. Hydrochlorothiazide at low dose is a frequent component of such biotherapies: it is efficacious and secure. Telmisartan is a highly selective blocker of angiotensin II AT1 receptors ("sartans"); it is at least as effective as the classical antihypertensive agents; thanks to its half-life, the longest of all sartans', it provides adequate antihypertensive coverage throughout the whole 24-hour postdose interval and particularly over the last 6 hours of the dosage interval. Its tolerability profile is equivalent to placebo. The combination telmisartan-hydrochlorothiazide is more effective than each agent alone at lowering blood pressure; furthermore telmisartan possesses a potassium-sparing effect that when the two drugs are coadministered attenuates the kaliuretic effect of hydrochlorothiazide. Various large trials are currently under way (ONTARGET, TRANSCEND, PROFESS, PROTECTION, DETAIL). These studies which together involve some 50,000 patients will hopefully help to further specify the role of telmisartan in condition which require an intervention on the renin-angiotensin system.
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PMID:[Kinzalkomb, a fixed telmisartan-hydrochlorothiazide combination for the treatment of hypertension]. 1462 54

Antihypertensive efficacy, effects on left ventricular mass index (LVMI) and tolerability of telmisartan, an angiotensin II receptor blocker, were compared with those of hydrochlorothiazide (HCTZ). Adult patients with mild-to-moderate hypertension and an optimal acoustic window by two-dimensional echocardiography were randomised at baseline to 12 months' double-blind, once-daily treatment with telmisartan 80 mg or HCTZ 25 mg. Two-dimensional echocardiography and freehand precordial three-dimensional echocardiography and 24-h ambulatory blood pressure monitoring were performed at baseline and after treatment. Of the 41 telmisartan group patients and 28 HCTZ group patients, 40 and 25, respectively, completed the study. Following treatment, 24-h mean SBP (telmisartan 157 +/- 11 vs 133 +/- 7 mmHg, P<0.001; HCTZ 154 +/- 10 vs 144 +/- 11 mmHg, P<0.003) and DBP (telmisartan 96 +/- 6 vs 83 +/- 5 mmHg, P<0.001; HCTZ 95 +/- 7 vs 87 +/- 8 mmHg, P<0.003) were significantly reduced. Telmisartan produced significantly greater 24-h mean SBP and DBP reductions than HCTZ (P<0.001). LVMI was significantly reduced by telmisartan (141 +/- 16 vs 125 +/- 19 g/m2, P<0.001), but not by HCTZ (139 +/- 20 vs 135 +/- 22 g/m(2)). Incidences of adverse events in both the treatment groups were low; two cases of hypokalaemia occurred with HCTZ. In conclusion, telmisartan 80 mg was well tolerated and significantly reduced SBP, DBP and LVMI after 12 months' treatment compared with HCTZ.
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PMID:Freehand three-dimensional echocardiographic evaluation of the effect of telmisartan compared with hydrochlorothiazide on left ventricular mass in hypertensive patients with mild-to-moderate hypertension: a multicentre study. 1468 11

Hypertension is one of the most important modifiable risk factors for cardiovascular pathology, such as atherosclerosis and cardiac left ventricular hypertrophy, including acute events such as stroke and myocardial infarction (MI). In particular, the risk of ischaemic and haemorrhagic stroke is directly and continuously related to high blood pressure levels. The renin-angiotensin system (RAS) plays an important role in volume homeostasis and blood pressure regulation. It also helps to prevent cell and organ damage from ischaemia during acute volume loss. However, angiotensin-II (A-II)--the main effector peptide of the RAS--also exerts a number of pathological effects, which are mediated by the AT 1 receptor. The Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial (ONTARGET) programme consists of two parallel trials where ONTARGET as a large, long-term study compares the efficacy of the angiotensin-receptor antagonist, telmisartan, the renin-angiotensin-converting enzyme (ACE) inhibitor, ramipril and combination therapy with telmisartan plus ramipril for reducing cardiovascular and cerebral risk. Telmisartan, due to its long duration of action, compares favourably with other angiotensin-receptor antagonists. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril was shown to reduce the risk for MI and other cardiovascular events in patients at high risk for pathological cardiac events, but without heart failure or a low ejection fraction. The cardiovascular outcomes of high-risk patients using the same criteria as those of the HOPE study will be assessed in both trials. TRANSCEND differs from ONTARGET in that this trial will enrol patients who do not tolerate ACE inhibitors. This parallel study will therefore be able to compare telmisartan and placebo treatment. Both ONTARGET and TRANSCEND trials feature the same primary composite end point: death caused by cardiovascular disease, acute MI, stroke and hospitalisation because of congestive heart failure. The secondary end points will focus on reductions in the development of Type 2 diabetes mellitus, nephropathy, cognitive decrease and dementia as well as atrial fibrillation.
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PMID:Challenges in improving prognosis and therapy: the Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial programme. 1515 18

Fifteen adult male spontaneously hypertensive rats (one year old) (SHR) were separated into three groups (n=5 each) during 15 weeks as follows: initial control group (IC); final control group (FC); and telmisartan group (T) (1.2 mg/kg/day of telmisartan). Serum and urinary creatinine and proteinuria were not different comparing untreated and telmisartan-treated SHRs. FC rats showed a continuous BP increase during the study while T rats reached the 15th week with a significantly low BP. The LV mass index was significantly smaller in the T group than in the FC group, as was the glomerular hypertrophy. The cardiomyocyte nuclei density per area and the cardiomyocyte mean cross-sectional area were smaller in the T group than in both the IC and FC groups. Intramyocardial artery densities (per area and per volume) were greater in the T group than in untreated SHRs, but myocardial fibrosis was reduced. In conclusion, telmisartan monotherapy effects on BP and also on the hypertension target organs, heart and kidney, are favorable. Telmisartan is able to attenuate SHR cardiomyocyte and glomerular hypertrophies, and myocardial reactive fibrosis as well. It also is favorable to the intramyocardial microcirculation.
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PMID:Effect of telmisartan on preexistent cardiac and renal lesions in spontaneously hypertensive mature rats. 1516 34

Telmisartan (Micardis) is a potent, long-lasting, nonpeptide angiotensin II type-1 (AT(1)) receptor blocker (ARB) that is indicated for the treatment of essential hypertension. In receptor binding studies, telmisartan showed a high affinity and selectivity for the human AT(1) receptors compared with AT(2) receptors and a slower dissociation rate from the human AT(1) receptor than those of ARBs. In isolated aorta rings, telmisartan was shown to be an insurmountable antagonist of AII-induced contractions. The inhibitory effects of telmisartan on AII-induced contraction persisted even after wash-out procedures. In animal models such as spontaneous hypertension rats and renovascular hypertensive rats, telmisartan produced the consistent reduction of blood pressure. Furthermore, there were no rebound phenomenon and no tolerance to the drug developed in the repeated oral administration. Telmisartan has a longer terminal elimination half-life (about 24 h) than the other ARBs. In patients with mild-moderate hypertension, trough/peak ratios for telmisartan were above 80%. In Japanese patients with mild-moderate hypertension, telmisartan produced a significant reduction in blood pressure (effective rate: 76.0%) with a good safety profile. Therefore, telmisartan is expected to be effective in the treatment of hypertension, producing sustained 24-h blood pressure control.
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PMID:[Pharmacological and clinical profile of telmisartan, a selective angiotensin II type-1 receptor blocker]. 1522 20

We evaluated the antihypertensive activity, glucose homeostasis and plasma lipid profile in patients with mild hypertension and type 2 diabetes mellitus treated by diet and exercise, and not in receipt of oral hyperglycemics, following 12-month treatment with either telmisartan or eprosartan. In this double-blind, placebo-controlled trial, 119 patients with mild essential hypertension (diastolic blood pressure [DBP] 91-104 mmHg) and type 2 diabetes were divided into three groups and randomized to receive once-daily telmisartan 40 mg, eprosartan 600 mg, or placebo for 12 months. At enrollment, patients were advised on diet (1,400-1,600 kcal/day) and exercise (physical aerobics on a bicycle for at least 30 min on 4 days each week). Compared with baseline, a significant reduction (p<0.01) in seated trough systolic blood pressure (SBP) was detected after 12-month treatment with either telmisartan or eprosartan. Seated trough DBP was also reduced by telmisartan (p<0.01) and eprosartan (p<0.05); the antihypertensive effect of telmisartan was significantly superior (p<0.05). No change in body mass index or glucose metabolism was observed with either active treatment, or with placebo. Telmisartan, but not eprosartan, significantly improved plasma total cholesterol (p<0.01), low-density lipoprotein cholesterol (p<0.01) and triglycerides (p<0.05) compared with eprosartan. In conclusion, 12-month telmisartan treatment produced a significantly greater reduction in DBP than eprosartan and significantly improved plasma lipids. The improvement could be due to varying pharmacokinetic/pharmacodynamic properties of telmisartan compared with eprosartan, even if it is not clear about the relationship between angiotensin-II receptor blockade and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition.
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PMID:Effects of telmisartan compared with eprosartan on blood pressure control, glucose metabolism and lipid profile in hypertensive, type 2 diabetic patients: a randomized, double-blind, placebo-controlled 12-month study. 1530 81

Telmisartan is an angiotensin-II receptor blocker that has demonstrated efficacy in the reduction of blood pressure in patients with hypertension. Patients with hypertension commonly require two or more antihypertensives to reduce their blood pressure to safe levels, and the choice of combination therapy should be informed by clinical trial data. Telmisartan is available in fixed-dose combination with hydrochlorothiazide (telmisartan/HCTZ) in doses of 40 mg/12.5 mg and 80 mg/12.5 mg. Telmisartan/HCTZ has been studied in a number of clinical trials in essential hypertension, for the most part using ambulatory blood pressure monitoring. It has been compared with monotherapy in full patient populations and in non-responders, and has been compared with other drug combinations. Telmisartan/HCTZ provides significantly greater reductions in blood pressure than monotherapy, and significantly increases the percentage of patients who achieve target blood pressure. The reduction in blood pressure achieved by adding HCTZ to telmisartan is greater than that achieved by adding HCTZ to atenolol, despite the fact that telmisartan and atenolol monotherapy had similar efficacy. Telmisartan/HCTZ provides significantly greater reductions than losartan plus HCTZ in 24-h mean blood pressure, primarily due to a significantly greater effect in the risky, early morning hours. Telmisartan/HCTZ is effective and well-tolerated in the elderly, diabetics and African-American patients. Ongoing studies are comparing the efficacy of telmisartan/HCTZ with valsartan plus HCTZ and amlodipine plus HCTZ in overweight, hypertensive diabetics and in patients with isolated systolic hypertension - two patient groups who are particularly at risk of target organ damage.
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PMID:Telmisartan/hydrochlorothiazide combination therapy in the treatment of essential hypertension. 1550 Mar 77

In theory, a drug that inhibits the renin-angiotensin system in order to lower blood pressure and acts as a PPARgamma agonist to increase insulin sensitivity, could be very useful in the treatment of coexisting Type 2 diabetes and hypertension. Telmisartan is an angiotensin Type 1 (AT(1))-receptor antagonist being used in the treatment of hypertension. Recent studies suggest that telmisartan is also a partial PPARgamma agonist. In an animal model of insulin resistance, telmisartan lowered serum levels of glucose, insulin and triglycerides, and body weight. Thus, telmisartan, an AT(1)-receptor antagonist and PPARgamma agonist, represents the prototype of a new approach to treating coexisting diabetes and hypertension, which needs to be evaluated clinically.
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PMID:Telmisartan - killing two birds with one stone. 1550 Mar 87

Type 2 diabetes mellitus is becoming a major health problem associated with excess morbidity and mortality. As the prevalence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a key objective in the near future. Besides lifestyle changes, various pharmacological treatments have proven their efficacy in placebo-controlled clinical trials, including antidiabetic drugs such as metformin, acarbose and troglitazone, or antiobesity agents such as orlistat. Arterial hypertension, a clinical entity in which insulin resistance is common, is strongly associated with type 2 diabetes and may precede the disease by several years. While antihypertensive agents such as diuretics or beta-adrenoceptor antagonists may worsen insulin resistance and impair glucose tolerance, newer antihypertensive agents exert neutral or even slightly positive metabolic effects. Numerous clinical trials have investigated the effects of ACE inhibitors or angiotensin II receptor antagonists (ARAs) on insulin sensitivity in hypertensive patients, with or without diabetes, with no consistent results. Almost half of the studies with ACE inhibitors in hypertensive nondiabetic individuals demonstrated a slight but significant increase in insulin sensitivity as assessed by insulin-stimulated glucose disposal during a euglycaemic hyperinsulinaemic clamp, while the other half failed to reveal any significant change. The effects of ARAs on insulin sensitivity are neutral in most studies. Mechanisms of improvement of glucose tolerance and insulin sensitivity through the inhibition of the renin-angiotensin system (RAS) are complex. They may include improvement of blood flow and microcirculation in skeletal muscles and, thereby, enhancement of insulin and glucose delivery to the insulin-sensitive tissues, facilitating insulin signalling at the cellular level and improvement of insulin secretion by the beta cells. Six recent large-scale clinical studies reported a remarkably consistent reduction in the incidence of type 2 diabetes in hypertensive patients treated with either ACE inhibitors or ARAs for 3-6 years, compared with a thiazide diuretic, beta-adrenoceptor antagonist, the calcium channel antagonist amlodipine or even placebo. The relative risk reduction averaged 14% (p = 0.034) in the CAPPP (Captopril Prevention Project) with captopril compared with a thiazide or beta1-adrenoceptor antagonist, 34% (p < 0.001) in the HOPE (Heart Outcomes Prevention Evaluation) study with ramipril compared with placebo, 30% (p < 0.001) in the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with lisinopril compared with chlortalidone, 25% (p < 0.001) in the LIFE (Losartan Intervention For Endpoint reduction in hypertension study) with losartan compared with atenolol, and 25% (p = 0.09) in the SCOPE (Study on Cognition and Prognosis in the Elderly) with candesartan cilexetil compared with placebo, and 23% (p < 0.0001) in the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trial with valsartan compared with amlodipine. All these studies considered the development of diabetes as a secondary endpoint, except the HOPE trial where it was a post hoc analysis. These encouraging observations led to the initiation of two large, prospective, placebo-controlled randomised clinical trials whose primary outcome is the prevention of type 2 diabetes: the DREAM (Diabetes REduction Approaches with ramipril and rosiglitazone Medications) trial with the ACE inhibitor ramipril and the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial with the ARA valsartan. Finally, ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) will also investigate as a secondary endpoint whether it is possible to prevent the development of type 2 diabetes by blocking the RAS with either an ACE inhibitor or an ARA or a combination of both. Thus, the recent consistent observations of a 14-34% reduction of the development of diabetes in hypertensive patients receiving ACE inhibitors or ARAs are exciting. From a theoretical point of view, they emphasise that there are many aspects of the pathogenesis, prevention and treatment of type 2 diabetes that still need to be uncovered. From a practical point of view, they may offer a new strategy to reduce the ongoing epidemic and burden of type 2 diabetes.
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PMID:Prevention of type 2 diabetes mellitus through inhibition of the Renin-Angiotensin system. 1551 53


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