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The value of irbesartan in the management of hypertension.
Bramlage, P, Durand-Zaleski, I, Desai, N, Pirk, O, Hacker, C
Expert opinion on pharmacotherapy. 2009;(11):1817-31
Abstract
Elevated blood pressure levels are highly prevalent and are a major reason for cardiovascular events and thus place a significant financial burden on healthcare systems worldwide. Guidelines recommend five first-line anti-hypertensive drug classes, but compelling indications may indicate favoring one drug class over another. Angiotensin receptor blockers (ARBs) have demonstrated a blood pressure lowering efficacy which is at least comparable with other drug classes, including ACE inhibitors (ACE-I), beta-blockers, calcium channel blockers and diuretics. They have, in addition, a lower side effect profile than other drug classes and patients on ARBs are more persistent with therapy. Compelling indications for the use of ARBs are heart failure, post-myocardial infarction, diabetic nephropathy, proteinuria/microalbuminuria, left ventricular hypertrophy, atrial fibrillation, metabolic syndrome and ACE-I induced cough. The ARB irbesartan has demonstrated a high efficacy in lowering blood pressure, which has been shown to be at least comparable with ACE-Is and superior to other ARBs such as losartan and valsartan. This translated into a better cost-effectiveness for irbesartan than for valsartan and losartan in the treatment of hypertension. In addition, irbesartan has been shown to be effective in both early and late stage diabetic nephropathy. It has further demonstrated considerable cost savings over standard therapy including beta-blockers, diuretics and non-dihydropyridine calcium channel blockers at all stages of kidney disease. Based on efficacy data from the Irbesartan Diabetic Nephropathy Trial and Reduction of Endpoints in NIDDM (non insulin dependant diabetes melitis) with the Angiotensin II Antagonist Losartan Study, it has also demonstrated cost savings over losartan in late stage renal disease. While both losartan and irbesartan are registered for the treatment of late stage diabetic nephropathy, irbesartan is also registered for early stage diabetic nephropathy in the EU. In summary, the data from randomized clinical trials on the efficacy of antihypertensive drugs provides an indication of their real value to patients. In addition observational data from clinical practice and proven end-organ protection in diabetic nephropathy provides further evidence of the true value of irbesartan compared to other ARBs in the treatment of hypertension.
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2.
Treatment of hypertension in metabolic syndrome subjects with amlodipine and olmesartan-effects on oxidized non-esterified free fatty acids and cytokine production.
Rosenson, RS
Cardiovascular drugs and therapy. 2009;(4):289-94
Abstract
PURPOSE Angiotensin II increases activation of oxidative signaling and vascular inflammatory gene expression, and interruption of the renin-angiotensin system has been considered more vasculoprotective than use of calcium channel antagonists and other anti-hypertensive therapies. Despite these putative mechanisms, amlodipine is equally efficacious as other therapies in reducing cardiovascular events. METHODS Double-blind, controlled trial, designed to investigate the effects of 2-months treatment with amlodipine and olmesartan on oxidized non-esterified fatty acids (ox-NEFA), and lipopolysaccharide-stimulated cytokine production in whole blood among 23 hypertensive subjects with the metabolic syndrome. RESULTS Treatment with olmesartan was no different than amlodipine in changing concentrations of total oxidized fatty acids (p = 0.37), total ox-NEFA (p = 0.43) and 9, 10, 11, 12, 13, 14, 15 and 16 ox-NEFA concentrations. In contrast, 8 ox-NEFA increased (median [interquartile ranges] by 45.2% [5.3 to 50.0] in olmesartan-treated subjects) compared with a decrease of 18.4% (-45.1-13.9) in amlodipine-treated subjects (p = 0.03). Lipopolysaccharide-stimulated cytokine production and levels of soluble cellular adhesion molecules did not change with either treatment. CONCLUSION Despite experimental data that demonstrates that angiotensin receptor antagonists reduce cellular oxidant stress and inflammation, olmesartan was not different than amlodipine in changing ox-NEFA and inflammatory markers in hypertensive subjects with the metabolic syndrome.
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3.
[Hypertensive patient with metabolic syndrome: would you prescribe a diuretic as the initial treatment? (interview by Thomas Meissner)].
Düsing, R
MMW Fortschritte der Medizin. 2008;(12):17
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Efficacy and tolerability of rilmenidine compared with isradipine in hypertensive patients with features of metabolic syndrome.
Widimský, J, Sirotiaková, J
Current medical research and opinion. 2006;(7):1287-94
Abstract
OBJECTIVES A high prevalence of associated metabolic cardiovascular risk factors is often observed among hypertensive subjects. The aim of the present study was to assess the effects of 1-2 mg/day of rilmenidine, a centrally acting antihypertensive agent with selectivity for I(1) imidazoline receptors, vs. 2.5-5 mg/twice daily of isradipine, a dihydropyridine calcium channel blocker, in hypertensive patients with features of the metabolic syndrome. RESEARCH DESIGN AND METHODS In this 6-month multicentre, comparative, double-blind, parallel group study, the primary objective was to assess the effects of the treatments on blood pressure (BP); the secondary endpoints were to assess glucose and lipid metabolism, in addition to clinical and biological tolerability. In non-responder patients, dose adjustment was possible from the first month and adding a diuretic from the third month. RESULTS Of an intention-to-treat population of 93 patients, 84 per protocol patients completed the study: 42 in the rilmenidine group and 42 in the isradipine group. BP decreased significantly (p < 0.001) and similarly in both groups (systolic blood pressure, SBP: -16.0 +/- 17.2 mmHg and -15.0 +/- 13.0 mmHg, and diastolic blood pressure, DBP: -9.0 +/- 9.4 mmHg and -9.0 +/- 8.7 mmHg with rilmenidine and isradipine, respectively). Normalisation (DBP < 90 mmHg and SBP < 140 mmHg) and response (normalisation or decrease in SBP >or= 20 mmHg or decrease in DBP >or= 10 mmHg) rates were respectively 57% and 72% with rilmenidine and 64% and 79% with isradipine (NS between groups). The effects of the treatments on both glucose and lipid metabolism were comparable: no significant difference from baseline was observed on the main parameters including insulin sensitivity indexes. The two treatments appeared to be well tolerated throughout the study, with no serious adverse reaction reported in the rilmenidine group and one serious adverse event in the isradipine group (a perimalleolar oedema), leading to withdrawal from the study for the affected patient. CONCLUSION This study suggests that in hypertensive patients with metabolic disorders, rilmenidine is an effective antihypertensive treatment, comparable to isradipine, with metabolic neutrality and a good tolerance profile.
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Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metformin.
Chazova, I, Almazov, VA, Shlyakhto, E
Diabetes, obesity & metabolism. 2006;(4):456-65
Abstract
AIM: To compare the effects of moxonidine and metformin on glycaemic control in patients with impaired glucose tolerance and signs of the metabolic syndrome. METHODS A multicentre, prospective, randomized, open-label study design was adopted with blinded endpoint evaluation. Patients > or =40 years old, with impaired glucose tolerance (or diabetes mellitus treated with diet alone) and a body mass index (BMI) of at least 27 kg/m2 were treated twice daily with moxonidine 0.2 mg or metformin 500 mg for 16 weeks. Oral glucose tolerance test (OGTT) was performed at baseline and end-of-study; plasma insulin and plasma glucose levels were measured at 0, 60, 120 and 180 min after administration. RESULTS With regard to effects on insulin [mean area under the curve (AUC) for insulin], the primary efficacy endpoint of the study, both drugs did not show equivalence. On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1-35.0). The change in mean insulin AUC was most marked in the subgroup of patients with higher sympathetic activity (heart rate >80 bpm). Mean fasting plasma glucose (FPG) levels and HbA1c levels were largely unchanged by moxonidine treatment but significantly decreased by metformin treatment. The difference between the groups was 14.7% (p = 0.0523) in the intent-to-treat (ITT) sample. By study end, both treatments had significantly increased the Matsuda Insulin Sensitivity Index (ISI) from baseline to a comparable extent: moxonidine by reducing plasma insulin after a glucose challenge, metformin by reducing FPG. BMI fell significantly in both groups and blood pressure normalized; both drugs were well tolerated. CONCLUSIONS Moxonidine improved insulin sensitivity in response to glucose challenge in patients with evidence of metabolic syndrome. This improvement resulted from a reduction in plasma insulin levels and was most marked in patients with high sympathetic drive at baseline. By enhancing insulin sensitivity, moxonidine treatment may help prevent the development of diabetes and thereby ameliorate the risk for cardiovascular disease.
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Chlorthalidone improves endothelial-mediated vascular responses in hypertension complicated by nondiabetic metabolic syndrome.
Dell'Omo, G, Penno, G, Del Prato, S, Pedrinelli, R
Journal of cardiovascular pharmacology and therapeutics. 2005;(4):265-72
Abstract
BACKGROUND The study was conducted to evaluate the vascular effects of chlorthalidone, a distal tubule-acting natriuretic agent, in hypertensive patients with nondiabetic metabolic syndrome, an insulin-resistant condition characterized by endothelial dysfunction and high risk for diabetes mellitus development. METHODS Thirteen untreated hypertensive patients with Adult Treatment Panel-III-defined nondiabetic metabolic syndrome were assigned to 3-month treatment with chlorthalidone. The end-points were baseline and post-treatment evaluation of (1) forearm blood flow (strain-gauge plethysmography) responses to graded intra-arterial acetylcholine infusion to test endothelial-mediated vasomotor function, with sodium nitroprusside as a control for endothelium-independent vasodilatation; (2) minimum forearm vascular resistance, the ratio of mean blood pressure and maximal blood flow in response to 13-minute arterial occlusion, as a hemodynamic correlate of arteriolar structure; and (3) transcapillary albumin escape rate (the 1-hour decay rate of (125)I-albumin, 6-8 microC ev) as a measure of systemic capillary permeability. Additional measurements included baseline and posttreatment lipids, fasting, and postload glucose and insulin as well as the homeostasis model assessment, an index of insulin sensitivity. RESULTS Chlorthalidone reduced blood pressure, augmented acetylcholine-mediated vasodilatation, decreased minimum forearm resistance, and slowed the transcapillary albumin escape rate. Metabolic parameters did not change significantly except for an increase in low-density lipoprotein cholesterol levels. CONCLUSIONS Chlorthalidone improved endothelial function, reversed abnormal arteriolar structure, and slowed albumin permeation in hypertensive patients with nondiabetic metabolic syndrome.
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Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial.
Bakris, GL, Fonseca, V, Katholi, RE, McGill, JB, Messerli, FH, Phillips, RA, Raskin, P, Wright, JT, Oakes, R, Lukas, MA, et al
JAMA. 2004;(18):2227-36
Abstract
CONTEXT Beta-blockers have been shown to decrease cardiovascular risk in patients with hypertension and type 2 diabetes mellitus (DM); however, some components of the metabolic syndrome are worsened by some beta-blockers. OBJECTIVE To compare the effects of beta-blockers with different pharmacological profiles on glycemic and metabolic control in participants with DM and hypertension receiving renin-angiotensin system (RAS) blockade, in the context of cardiovascular risk factors. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, parallel-group trial (The Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives [GEMINI]) conducted between June 1, 2001, and April 6, 2004, at 205 US sites that compared the effects of carvedilol and metoprolol tartrate on glycemic control. The 1235 participants were aged 36 to 85 years with hypertension (>130/80 mm Hg) and type 2 DM (glycosylated hemoglobin [HbA1c], 6.5%-8.5%) and were receiving RAS blockers. Participants were followed up for 35 weeks. INTERVENTIONS Participants were randomized to receive a 6.25- to 25-mg dose of carvedilol (n = 498) or 50- to 200-mg dose of metoprolol tartrate (n = 737), each twice daily. Open-label hydrochlorothiazide and a dihydropyridine calcium antagonist were added, if needed, to achieve blood pressure target. MAIN OUTCOME MEASURES Difference between groups in mean change from baseline HbA1c following 5 months of maintenance therapy. Additional prespecified comparisons included change from baseline HbA1c in individual treatment groups, treatment effect on insulin sensitivity, and microalbuminuria. RESULTS The 2 groups differed in mean change in HbA1c from baseline (0.13%; 95% confidence interval [CI], -0.22% to -0.04%; P = .004; modified intention-to-treat analysis). The mean (SD) HbA1c increased with metoprolol (0.15% [0.04%]; P<.001) but not carvedilol (0.02% [0.04%]; P = .65). Insulin sensitivity improved with carvedilol (-9.1%; P = .004) but not metoprolol (-2.0%; P = .48); the between-group difference was -7.2% (95% CI, -13.8% to -0.2%; P = .004). Blood pressure was similar between groups. Progression to microalbuminuria was less frequent with carvedilol than with metoprolol (6.4% vs 10.3%; odds ratio, 0.60; 95% CI, 0.36-0.97; P = .04). CONCLUSIONS Both beta-blockers were well tolerated; use of carvedilol in the presence of RAS blockade did not affect glycemic control and improved some components of the metabolic syndrome relative to metoprolol in participants with DM and hypertension. The effects of the 2 beta-blockers on clinical outcomes need to be compared in long-term clinical trials.
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Effect of doxazosin on the size of LDL particle in the type 2 diabetic patients with hypertension.
Tamasawa, N, Matsui, J, Ogawa, Y, Gotoh, T, Hinata, T, Murakami, H, Zhi, GJ, Suda, T
Journal of diabetes and its complications. 2000;(3):135-9
Abstract
Hypertension is common in patients with type 2 diabetes mellitus (DM), and contributes to the progression of its complications in patients with diabetes. Doxazosin is a selective alpha1-adrenoceptor-blocking anti-hypertensive agent and has a favorable impact upon lipid metabolism. We investigated the effect of doxazosin on the lipid metabolism in hypertensive patients with type 2 diabetes, especially low-density lipoprotein (LDL) particle size that is associated with many elements of the insulin resistance syndrome. Cross-sectional study (n=19) was designed to determine whether doxazosin, administered with an angiotensin II-converting enzyme inhibitor (ACEI) and a Ca antagonist, affects LDL particle size. As a follow-up study (n=6), lipid and glucose metabolism and LDL particle size were followed for 12 weeks before and after the initiation of doxazosin administration (1-4 mg/day). The average size of LDL particle was significantly larger in the patients treated with doxazosin (LDL-migration index (LDL-MI): 0.348+/-0.027) than those in the patient treated without doxazosin (0.378+/-0.035), although LDL cholesterol levels did not differ between the two groups. The plasma glucose and HbA1c levels remained unchanged. Lipid profile showed normolipemia throughout the period of the study. However, LDL particle size was demonstrated to become larger during the following period. Small LDL fraction (LDL3-7) diminished remarkably and large LDL (LDL1-2) increased on the polyacrylamide gel electrophoresis (PAGE) LDL system (LipoPrint). From this pilot study, it was concluded that doxazosin is a useful anti-hypertensive agent for hypertensive type 2 diabetic patients in improving the size of LDL particle.