Avapro scientific update |
|
 |
|
J Clin Pharm Ther. 2007 Jun;32(3):261-8.
Derosa G, Fogari E, D'Angelo A, Cicero AF, Salvadeo SA, Ragonesi PD, Ferrari I, Gravina A, Fassi R, Fogari R.
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Metabolic effects of telmisartan and irbesartan in type 2 diabetic patients with metabolic syndrome treated with rosiglitazone.
Treatment for type 2 diabeties using rosiglitazone in type 2 diabetic patients with metabolic syndrome and the metabolic effect of telmisartan and irbesartan. Background and objective: Angiotensin II receptor blockers represent a class of effective and well-tolerated orally
active antihypertensive drugs in the general hypertensive population and in diabetic patients. The aim of our study
was to investigate the metabolic effects of telmisartan and irbesartan in diabetic subjects treated with
rosiglitazone. Methods: We evaluated 188 type 2 diabetic patients with metabolic syndrome. All patients took a
fixed dose of 4 mg rosiglitazone/day. We administered 40 mg telmisartan/day or 150 mg irbesartan/day and evaluated
their body mass index, glycosylated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), fasting plasma insulin
(FPI), homeostasis model assessment-index (Homa-IR), total cholesterol (TC), low density lipoprotein-cholesterol
(LDL-C), high density lipoprotein-cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure,
adiponectin and resistin during 12 months of this treatment. Results and discussion: In addition to a comparable
antihypertensive effect for telmisartan and irbesartan after 6 and 12 months, both treatments were associated with
a significant reduction in TC and LDL-C plasma levels compared with baseline. After 6 months of treatment, only the
telmisartan group experienced a significant improvement in (HbA(1c)), FPG, Homa-IR, adiponectin and resistin
compared with the baseline values, whereas both drug regimens were associated with a significant improvement in
these parameters after 12 months. However, the improvements observed in the telmisartan group were significantly
larger than that noted in the irbesartan group after 12 months of treatment. FPI significantly decreased only after
12 months of treatment in both groups, but again, the reduction was significantly larger in the telmisartan-treated
subjects. Conclusions: Telmisartan seemed to improve glycaemic and lipid control and metabolic parameters of the
metabolic syndrome better than irbesartan. These differences could be relevant in the choice of therapy for this
condition and diabetes.
Nephrol Ther. 2007 Apr;3(2):65-68. Epub 2007 Apr 6.
Weclawiak H, Ribes D, Modesto A, Kamar N, Durand D, Rostaing L.
Department de nephrologie, dialyse et transplantation d'organes, CHU de Rangueil, 1, avenue Jean-Poulhes, TSA 50032 Toulouse cedex 09, France.
[Efficiency of rituximab treatment for recurrence of membranous glomerulopathy after renal transplantation.][Article in French]
Reappearance of membranous glomerulopathy after renal transplantation and the effect of rituximab treatment. Idiopathic membranous glomerulonephritis (MGN) is a rare cause of end-stage renal failure, which can lead to
chronic hemodialysis. This glomerulopathy can recur after renal transplantation despite immunosuppressive therapy.
To date, there is no confirmed therapy for treatment of renal grafts after recurrence of MGN. Herein, we report on
a 27-year-old man who underwent cadaveric renal transplantation for MGN in September 2001. At 2 months
posttransplant, a renal biopsy showed membranous deposition on immunofluorescence staining evocative of recurrence
of MGN. Proteinuria developed progressively and, at one year, was estimated at 7.65 g/24 h, with hypoalbuminemia of
24 g/l. This persisted despite symptomatic treatment with anti-proteinuric agents (enalapril 20 mg/day and
irbesartan 75 mg/day) and atorvastatin (10 mg/day). By March 2004, his proteinuria was 11 g/day; therefore, therapy
with rituximab (monoclonal anti-CD20) at 375 mg/m(2) weekly was initiated for four consecutive weeks, followed by
the same dosage every four months for one year. Biological controls performed two weeks after the fourth infusion
of rituximab showed a fall in proteinuria, assessed at 1 g/24 h, with albuminemia of 29 g/l and normalized lipidic
results. A renal biopsy performed 6 months after the first infusion was unchanged. Follow-up at 30 months showed
consistent remission of membranous nephropathy, demonstrated by a serum creatinine level of 150 mumol/L,
microalbuminuria of 107 mg/24 h and normal albuminemia of 43.7 g/l. There were no side effects; in particular, no
infectious complications occurred, despite CD19 lymphocytes being still negative after 30 months. Monoclonal CD-20
antibodies have shown efficacy against MGN compared to conventional therapies in native kidneys. It has recently
been shown that CD20 mRNA is overexpressed in the renal interstitium in patients suffering from MGN and that the
interstitial infiltrates is mainly composed of B-cell lymphocytes in these patients. These data may explain the
efficiency of rituximab in these circumstances.
Cardiovasc Diabetol. 2007 Apr 3;6:12.
Kintscher U, Bramlage P, Paar WD, Thoenes M, Unger T.
Center for Cardiovascular Research, Institute of Pharmacology, Charite, Berlin, Germany.
Irbesartan for the treatment of hypertension in patients with the metabolic syndrome: a sub analysis of the Treat to Target post authorization survey. Prospective observational, two armed study in 14,200 patients.
A sub analysis of the Treat to Target post authorization survey on the treatment using irbesartan in patients with hypertension and metabolic syndrome. A study conducted in 14,200 patients. OBJECTIVES: The metabolic syndrome is a cluster of cardiovascular risk factors leading to an increased risk for the
subsequent development of diabetes and cardiovascular morbidity and mortality. Blocking the renin-angiotensin
system has been shown to prevent cardiovascular disease and delay the onset of diabetes. Irbesartan is an
angiotensin receptor blocker (ARB) which has been shown to possess peroxisome proliferator-activated receptor gamma
(PPARgamma) activating properties, and to have a favorable metabolic profile. Current discussion is whether the
addition of small doses of hydrochlorothiazide changes this profile. Therefore the efficacy, safety and metabolic
profile of Irbesartan either as monotherapy or in combination therapy was assessed in patients with the metabolic
syndrome in a large observational cohort in primary care. RESEARCH DESIGN AND METHODS: Multicenter, prospective,
two-armed, post authorization study over 9 months in 14,200 patients with uncontrolled hypertension with and
without the metabolic syndrome (doctors' diagnosis based on the Adult Treatment Panel III criteria 2001). Blood
pressure was measured sphygmomanometrically and cardiovascular risk factors making up the criteria for the
metabolic syndrome were assessed. MAIN OUTCOME MEASURES: Systolic (SBP) and diastolic (DBP) blood pressure
reduction, response, and normalization (systolic and diastolic), changes in fasting glucose, waist circumference
(abdominal obesity), serum triglycerides and HDL cholesterol as well as the proportion of patients fulfilling the
criteria for the metabolic syndrome. Number and nature of adverse events (AEs). RESULTS: After 9 month the use of
Irbesartan in monotherapy resulted in a significant reduction of blood pressure (SBP: -26.3 +/- 10.1 mmHg/DBP-13.0
+/- 6.6 mmHg, both p < 0.0001) in patients with the metabolic syndrome. This was accompanied by a reduction in
cardiovascular risk factors: HDL cholesterol (+3.6 +/- 7.2 mg/dl in men, +3.8 +/- 6.5 mg/dl in women, both p <
0.0001), serum triglycerides (-28.6 +/- 52.1 mg/dl, p < 0.0001), fasting blood glucose (-8.4 +/- 25.1 mg/dl, p <
0.0001) and waist circumference (-2.4 +/- 11.9 cm in men, -1.2 +/- 14.2 in women, both p < 0.0001) were
significantly improved. Irbesartan combination therapy (12.5 mg HCTZ) in patients with the metabolic syndrome:
blood pressure reduction (SBP: -27.5 +/- 10.1 mmHg/DBP: -14.1 +/- 6.6 mmHg, both p < 0.0001), improvement in HDL
cholesterol (+4.0 +/- 6.8 mg/dl in men, +3.4 +/- 6.8 in women, both p < 0.0001), triglycerides (-34.1 +/- 52.6
mg/dl, p < 0.0001), fasting blood glucose (-10.0 +/- 24.7, p < 0.0001) and waist circumference (-3.2 +/- 12.7 cm in
men, -1.7 +/- 14.4 in women, both p < 0.0001). Tolerability was excellent: only 0.6% of patients experienced an AE.
CONCLUSION: There was a significant improvement in blood pressure and metabolic risk factors as a result of
Irbesartan treatment. There was no evidence of a difference between monotherapy and combination therapy with regard
to the cardiovascular risk profile.
Am J Kidney Dis. 2006 Oct;48(4):571-9.
Busch M, Franke S, Wolf G, Brandstadt A, Ott U, Gerth J, Hunsicker LG, Stein G; Collaborative Study Group.
epartment of Internal Medicine III and Institute of Medical Statistics and Computer Sciences, University of Jena, Germany.
The advanced glycation end product N(epsilon)-carboxymethyllysine is not a predictor of cardiovascular events and renal outcomes in patients with type 2 diabetic kidney disease and hypertension.
N(epsilon)-carboxymethyllysine, an advanced glycation end product, is not a predictor of cardiovascular events and renal outcomes in type 2 diabetic patients with kidney disease and hypertension. BACKGROUND: Advanced glycation end products (AGEs) are implicated in the pathogenesis of vascular damage, especially in patients with diabetes and renal insufficiency. The oxidatively formed AGE N(epsilon)-carboxymethyllysine (CML) is thought to be a marker of oxidative stress. METHODS: Four hundred fifty patients with type 2 diabetes and nephropathy from the Irbesartan in Diabetic Nephropathy Trial cohort (mean age, 58 +/- 8.2 years; 137 women, 313 men) with a mean glomerular filtration rate of 48.2 mL/min (0.80 mL/s; Modification of Diet in Renal Disease formula) were followed up for 2.6 years. Serum CML was measured by using an enzyme-linked immunosorbent assay. Relationships between CML levels, traditional risk factors, and cardiovascular and renal events were tested in Cox proportional hazards models. RESULTS: Mean serum CML level was 599.9 +/- 276.0 ng/mL, and mean hemoglobin A1c level was 7.5% +/- 1.6%. One hundred forty-three first cardiovascular events occurred during follow-up; 74 patients died, 44 of cardiovascular causes. Final multivariate analysis showed age (relative risk [RR], 1.87; confidence interval [CI], 1.13 to 3.11; P = 0.016 for the highest compared with lowest quartile), history of prior cardiovascular events (RR, 1.96; CI, 1.35 to 2.85; P < 0.0005), and 24-hour urinary albumin-creatinine ratio (RR, 1.29; CI, 1.11 to 1.50 per doubling; P < 0.0005) to be independent risk factors for a first cardiovascular event, but not CML level. CML level also did not correlate significantly with renal outcome. CONCLUSION: Serum CML level could not be identified as an independent risk factor for cardiovascular or renal outcomes in the examined population. This suggests that traditional risk factors might have a more important role for these end points or that other AGE compounds, as well as tissue AGE levels, might be of greater relevance compared with serum levels, which remains open to further study.
Circulation. 2005 Jan 25;111(3):343-8. Epub 2005 Jan 17.
Sola S, Mir MQ, Cheema FA, Khan-Merchant N, Menon RG, Parthasarathy S, Khan BV.
Division of Cardiology, Emory University School of Medicine, Atlanta, Ga 30303, USA.
Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study.
In the case of metabolic syndrome, Irbesartan and lipoic acid can improve endothelial function and decrease markers of inflammation according to the Endothelial Dysfunction (ISLAND) study. BACKGROUND: The metabolic syndrome is associated with increased angiotensin II activity, induction of a proinflammatory and oxidative state, and endothelial dysfunction. We evaluated the ability of irbesartan, an angiotensin receptor blocker, and lipoic acid, an antioxidant, to affect endothelial function and inflammation in patients with the metabolic syndrome. METHODS AND RESULTS: We randomized 58 subjects with the metabolic syndrome in a double-blinded manner to irbesartan 150 mg/d (n=14), lipoic acid 300 mg/d (n=15), both irbesartan and lipoic acid (n=15), or matching placebo (n=14) for 4 weeks. Endothelium-dependent and -independent flow-mediated vasodilation was determined under standard conditions. Plasma levels of interleukin-6, plasminogen activator-1, and 8-isoprostane were measured. After 4 weeks of therapy, endothelium-dependent flow-mediated vasodilation of the brachial artery was increased by 67%, 44%, and 75% in the irbesartan, lipoic acid, and irbesartan plus lipoic acid groups, respectively, compared with the placebo group. Treatment with irbesartan and/or lipoic acid was associated with statistically significant reductions in plasma levels of interleukin-6 and plasminogen activator-1. In addition, treatment with irbesartan or irbesartan plus lipoic acid decreased 8-isoprostane levels. No significant changes in blood pressure were noted in any of the study groups. CONCLUSIONS: Administration of irbesartan and/or lipoic acid to patients with the metabolic syndrome improves endothelial function and reduces proinflammatory markers, factors that are implicated in the pathogenesis of atherosclerosis.
J Hypertens. 2005 Mar;23(3):633-40.
Muller-Brunotte R, Edner M, Malmqvist K, Kahan T.
Division of Internal Medicine, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden.
Irbesartan and atenolol improve diastolic function in patients with hypertensive left ventricular hypertrophy.
In patients with in patients with hypertensive left ventricular hypertrophy, the diastolic function can be improved by Irbesartan and atenolol. OBJECTIVES AND DESIGN: An abnormal diastolic filling is common in hypertensive left ventricular (LV) hypertrophy, a condition that may lead to heart failure and death. The renin-angiotensin-aldosterone system has been implicated in the development of LV hypertrophy. This study examines the effects of 48 weeks of double-blind treatment with the AT1 receptor blocker irbesartan and the beta-blocker atenolol on diastolic function. METHODS: Diastolic function was evaluated in 115 hypertensive patients with LV hypertrophy by Doppler echocardiography mitral inflow velocities calculated from the peak of early (E) and peak of late (A) diastolic velocities (E/A ratio), the E-wave deceleration time, the isovolumic relaxation time, the pulmonary venous flow velocity, and by the atrioventricular valve plane displacement method. RESULTS: By similar reductions in blood pressure both groups progressively reduced the LV mass index, with a greater reduction in the irbesartan group (P = 0.024). Diastolic function was improved similarly by irbesartan and atenolol; for example, the E/A ratio by 12 and 14% (P = 0.022 and P < 0.001), and the pulmonary venous flow velocity by 10 and 7% (P = 0.036 and P = 0.001), respectively. The isovolumic relaxation time was improved by irbesartan (P = 0.040) only, and was related to changes in LV geometry (P < 0.001). For atenolol, improvement in diastolic function was associated only with the reduction in blood pressure (P = 0.048). An improvement in diastolic function appeared greater in concentric LV hypertrophy than in eccentric LV hypertrophy. CONCLUSIONS: Treatment based on atenolol or irbesartan improves diastolic function in patients with hypertensive LV hypertrophy to the same degree, but through different mechanisms.
Nephrol Dial Transplant. 2005 Apr 26; [Epub ahead of print]
Palmer AJ, Tucker DM, Valentine WJ, Roze S, Gabriel S, Cordonnier DJ.
CORE - Center for Outcomes Research, Bundtenmattstrasse 40, 4102 Binningen, Switzerland.
Cost-effectiveness of irbesartan in diabetic nephropathy: a systematic review of published studies.
A systematic review of published studies on cost-effectiveness of irbesartan in diabetic nephropathy. BACKGROUND: To review published studies on the cost-effectiveness of the use of irbesartan for treatment of advance overt nephropathy in patients with type 2 diabetes and hypertension. METHODS: Articles were identified based on a search of the PubMed databases using the keywords 'irbesartan', 'ESRD', 'cost-effectiveness', 'nephropathy' and 'costs', and by personal communication with the authors. Only studies published in the last 10 years were included. All costs data from the cost-effectiveness studies were inflated to 2003 Euros using published governmental conversion tables. RESULTS: Seven published studies were identified, spanning the following country settings: the US, Belgium and France, Germany, Hungary, Italy, Spain, and the UK. In each, the same pharmacoeconomic model was adapted using country-specific data to project and evaluate the clinical and cost outcomes of the treatment arms of the Irbesartan in Diabetic Nephropathy Trial (IDNT) (irbesartan, amlodipine or standard blood pressure control). Mean time to onset of ESRD was 8.23 years for irbesartan, 6.82 years for amlodipine and 6.88 years for the control (values were the same for Belgium, France, Germany, Hungary, Italy and Spain as transition probabilities for progression to ESRD were all derived from the IDNT). Mean cumulative incidence of ESRD was 36% with irbesartan, 49% with amlodipine and 45% with control treatment. Treatment with irbesartan was projected to improve life expectancy compared to both amlodipine and control in all seven published studies. Analysis of total lifetime costs showed that irbesartan treatment was cost saving compared to the other two treatment regimens, due to the associated reduction in ESRD cases. Cost savings with irbesartan became evident very early; after 2-3 years of treatment in most settings. CONCLUSIONS: Modelling studies based on the IDNT published to date suggest that irbesartan treatment in patients with type 2 diabetes, hypertension and advanced nephropathy is both life- and cost-saving compared to amlodipine or control.
Circulation. 2005 May 2; [Epub ahead of print]
Ceriello A, Assaloni R, Da Ros R, Maier A, Piconi L, Quagliaro L, Esposito K, Giugliano D.
Department of Pathology and Medicine, Experimental and Clinical, Chair of Internal Medicine, University of Udine, Udine.
Effect of Atorvastatin and Irbesartan, Alone and in Combination, on Postprandial Endothelial Dysfunction, Oxidative Stress, and Inflammation in Type 2 Diabetic Patients.
Efficacy of Atorvastatin and Irbesartan, alone and in combination, can act on Postprandial Endothelial Dysfunction, Oxidative Stress, and Inflammation in Type 2 Diabetic patients. BACKGROUND: Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction and inflammation through oxidative stress. Statins and angiotensin type 1 receptor blockers have been shown to reduce oxidative stress and inflammation, improving endothelial function. METHODS AND RESULTS: Twenty type 2 diabetic patients ate 3 different test meals: a high-fat meal, 75 g glucose alone, and a high-fat meal plus glucose. Glycemia, triglyceridemia, endothelial function, nitrotyrosine, C-reactive protein, intercellular adhesion molecule-1, and interleukin-6 were assayed during the tests. Subsequently, diabetics took atorvastatin 40 mg/d, irbesartan 300 mg/d, both, or placebo for 1 week. The 3 tests were performed again between 5 and 7 days after the start of each treatment. High-fat load and glucose alone produced a decrease in endothelial function and increases in nitrotyrosine, C-reactive protein, intercellular adhesion molecule-1, and interleukin-6. These effects were more pronounced when high-fat load and glucose were combined. Short-term atorvastatin and irbesartan treatments significantly counterbalanced these phenomena, and their combination was more effective than either therapy alone. CONCLUSIONS: This study confirms an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function and inflammation, suggesting oxidative stress as a common mediator of such an effect. Short-term treatment with atorvastatin and irbesartan may counterbalance this phenomenon; the combination of the 2 compounds is most effective.
Avapro description...
|
|
Drug category:Hypotensive agents
 Avapro scientific update
|
|
My Basket